Hybrid Cervical Surgery
Expandable Vs Static Interbody Cages Biologic Therapies for Degenerative Disc Disease Wound Complications and Management in Thoracolumbar Spine Surgery Efficacy of Denosumaby The Intersection of Predictive Machine Learning and Spine Surgery Practice Mental Workload Stress in Orthopedic and Spine Surgeons
COLUMNS International Society for the Advancement of Spine Surgery
The Surgical Learning Curve
PROFICIE N CY
Beyond the Operating Room
Vertebral
PROCEDURES
FA L L 20 26
Intraoperative Neuromonitoring in Cervical Myelopathy
Fall 2026 Editor in Chief Kern Singh, MD Associate Editor Daniel K. Park, MD
EDITORIAL 3 The Surgical Learning Curve: From Learning to
Editorial Board
9 Hybrid Cervical Surgery: “Experimental” or Well-Studied
Sravisht Iyer, MD
Mastering
CERVICAL SPINE
Technique?
CERVICAL SPINE 14 Intraoperative Neuromonitoring in Cervical Myelopathy: Are We Using It or Just Ordering It?
MEDICAL DEVICES 21 Expandable Vs Static Interbody Cages: What the Current Evidence Supports
BIOLOGICS 27 Biologic Therapies for Degenerative Disc Disease: Where Do PRP and Cell-Based Therapies Stand in 2026?
Brandon Hirsch, MD
Nathan J. Lee, MD Yu-Po Lee, MD Sheeraz Qureshi, MD, MBA Arash J. Sayari, MD Managing Editor Audrey Lusher Designer CavedwellerStudio.com
COMPLICATIONS 36 Wound Complications and Management in Thoracolumbar Spine Surgery
COMPLICATIONS 42 Efficacy of Denosumab: Reducing Fracture Risk and Complications After Surgery
NEW TECHNOLOGY 46 The Intersection of Predictive Machine Learning and Spine Surgery Practice
PHYSICIAN WELLNESS 52 Mental Workload Stress in Orthopedic and Spine Surgeons
BUSINESS OF MEDICINE 57 Beyond the Operating Room: The Growing Role of Business Education in Spine Surgery
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Vertebral Columns is published quarterly by the International Society for the Advancement of Spine Surgery. ©2026 ISASS. All rights reserved. Opinions of authors and editors do not necessarily reflect positions taken by the Society. This publication is available digitally at https://isass.org/category/news/ vertebral-columns/
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From the 1Department of Orthopaedic Surgery at Rush University Medical Center in Chicago, Illinois; 2School of Medicine at Case Western Reserve University in Cleveland, Ohio; and 3College of Medicine at The Ohio State University in Columbus, Ohio.
EDITORIAL
The Surgical Learning Curve:
Dipankar Yettapu, BS1,2
From Learning to Mastering Spine surgery has seen a rapid adoption of new technologies–endoscopic techniques, robotic-assisted navigation, and augmented reality guidance–each promising better outcomes, shorter operative times, or greater cost-efficiency. But adopting any new technique carries a learning curve: the period during which the surgeon’s performance, measured by metrics like operative time or complication rate, improves with case volume before remaining stable. Patients treated early in this period can theoretically face higher surgical risks. Despite being widely acknowledged, the spine literature lacks a consistent framework for defining or quantifying the learning curve, with studies using inconsistent methods and reporting case-number thresholds that vary widely even within the same technolog y. This review aims to (1) define the learning curve concept in spine surgery, (2) evaluate the methods used to quantify it, (3) characterize case-number benchmarks across endoscopic, robotic, and navigation/ augmented reality (AR) techniques, and (4) propose strategies to shorten this gap and reduce its impact on patient safety.
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Defining the Learning Curve The learning curve was first described in manufacturing and has since been applied in medicine. In surger y, it is defined as “the time taken and/or the number of procedures an average surgeon needs to be able to perform a procedure independently with a reasonable outcome.”1 The operation or procedure time will decrease initially, then stabilize as time passes. With experience, complications and adverse events will also decrease. Outcomes of interest over the learning curve include increased patient survival rates, patient recovery metrics, and other measures of successful surgery. There are several established methodological frameworks that have been used for quantifying progress of the surgical learning curve. A 2024 systematic rev iew of 113 studies considered various t ypes of statistical approaches commonly used, including intervals, regression, and cumulative sum (CUSUM) analysis. 2 Inter vals were described as the simplest technique, where researchers can choose a means to divide cases into intervals and differentiate the chosen metrics between the groupings. However, this
Madeline Sandberg, BS1
Jonah Dujovny, BS1
Maximilian Y. Lee, BS1,3
Rohit Rajput, BA1
Daniel K. Park, MD1
Kern Singh, MD1
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EDITORIAL
analysis falls short in terms of its consistency across various studies. Regression analysis helps to establish a relationship between dependent and independent variables within a study, though it is subject to outliers. CUSUM analysis is used to track how metrics differ over time compared to a benchmark, but it too has drawbacks such as logistical limitations. Another important distinction in surgical learning curves is the choice of outcome metrics. Interestingly, the review noted that 66 of the studies used only a single metric. The most common measure used
was operative time, while others included blood loss, complication rate, fluoroscopy time, reoperation rate, or screw accuracy. Outcomes measures can vary as various surgical technologies aim to improve a certain parameter of surgery and not all measures. Risk-adjusted CUSUM is a type of CUSUM that takes into account the risk of potential complications for patients against the actual outcome (Table). 3 Studies have also utilized the moving averages approach to show how frequent an event occurs over a given time period.4
Table. Learning Curve Methods
Method
Definition
Strengths
Limitations
Chronological Grouping
Cases are split into blocks in the order they happened (eg, first 20 cases vs next 20), and outcomes are compared between blocks.24
The simplest method to run and to explain; requires no special statistics.
Where researchers draw the block lines is arbitrary, which makes it hard to compare results between studies. It also tends to miss clusters of complications that happen close together in time.12,24
Regression / Curve-Fitting
A mathematical curve is fitted to the data (like operative time vs case number), and the point where the curve flattens out marks the end of the learning phase.24
Considered by statisticians to be one of the more defensible approaches; it uses every case in the dataset rather than just comparing a few blocks.24
There's no agreed-upon “right” shape for the curve, so different researchers can fit different models to the same data and get different answers. And reaching a flat, stable curve doesn't necessarily mean a surgeon has become safer—just more consistent.24
Cumulative Sum (CUSUM)
Running tally that adds up how far each case's result (usually operative time) differs from a benchmark, plotted case by case. The most common version compares each case to the surgeon's own overall average.24
Popular and visually easy to read. When it's built around a fixed, predefined target set before the study begins, researchers consider it one of the more reliable methods available.24
The most common version of this method, though, compares each case to the surgeon's own average from that same case series— and that setup tends to force the line to rise and then fall back to zero by the end, whether or not real learning happened. Statisticians who studied this in detail found this common version is “frequently interpreted incorrectly” and recommended against using it.24
Risk-Adjusted CUSUM (RACUSUM)
A more advanced version of CUSUM that adjusts the benchmark for each patient's individual risk factors (age, health conditions, complexity of the case) rather than comparing every case to one flat average.3,25
Corrects for a major source of bias: surgeons often pick easier cases while they're still learning a new technique, which can make a raw CUSUM look better than it should. In the spine studies examined here, this method found that surgeons needed more cases to reach safe, stable performance than a standard CUSUM suggested.3,25
Needs a well-built statistical model of patient risk to work properly—if that risk model is flawed, the results can be misleading.3
LearningCurve CUSUM (LC-CUSUM)
A CUSUM variant that sets a specific target in advance (for example, “operative time under 160 min”) and signals the moment a surgeon reliably meets that bar, instead of just showing a general trend.25
Gives a clear, pre-defined finish line rather than an after-the-fact interpretation of a graph. In one multi-surgeon spine study, this method also revealed how much learning speed can vary between individual surgeons.25
Still requires researchers to decide, in advance, what counts as “good enough” performance—a judgment call that can vary from study to study.25
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EDITORIAL
Surgical learning curves aim to identify an inflection point where learning reaches a maximum. Jacob et al5 discussed how this plateau is statistically identified through lateral lumbar interbody fusions from a single surgeon. In the study it was noted that linear piecewise regression was used to identify the breakpoint where the cases were grouped into “learning” and “proficient.” Linear regression showed no change in the outcome metric from case 53 through 179, and thus case 53 was established as the breakpoint. Heterogeneity in defining “proficiency,” “mastery,” and “expertise” contributes to less reliable reporting of surgical learning curves.6
Discrete Learning Curve Case Counts Different t y pes of surger y have var ying case-number thresholds that have been established as benchmarks. For endoscopic spine surgery, a 2026 systematic review of 29 studies found that, on average, 20 cases were needed to meet the threshold for uniportal surgery and 37.5 cases for biportal surgeries.7 However, individual surgeons may have different experiences. One study reported a threshold of 31 cases to gain proficiency in biportal endoscopic lumbar decompression.8 In robotic-assisted spine surgery, a systematic review of 14 studies specifically focused on pedicle screw placement found metric-specific thresholds. On average, 80% improvement in operating time occurs after 46 cases, and 90% of surgeons plateaued after 369.1 cases. Screw accuracy on average reached 80% of improvement after 217 screws. Blood loss reached 80% improvement on average
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after 65 cases.9 No surgical learning curve was found for complications. The systematic review on endoscopic spine surgery notably only utilized operative time as an outcome, whereas the robotic-assisted spine surgery study evaluated numerous other metrics. AR-guided techniques are newer and thus the data are less robust. However, a 2023 study using AR for pedicle screw placement found that surgeon performance did not differ significantly between early and later cases, showing no distinct learning curve for this technique.10
Balancing New Technology Adoption and Technique Proficiency An important aspect of establishing an acceptable learning curve is to balance the trade-off between innovation adoption and patient safety during the learning phase. Advancement of new surgical techniques and procedures is necessary for the advancement of medicine, but it comes at a cost as surgeons may work slower or with possibly higher complication rates during this process. This trade-off has been investigated for esophagectomies, where investigators found that leakage decreased significantly from the learning phase to the endpoint.11 Furthermore, surgical learning curves can be established with risk-adjusted/complication-based thresholds, where thresholds are achieved at specific complication rates or are purely time based, where a specific time efficiency must be achieved. Sclafani and Kim12 discussed both a complication-based threshold and a time-based one in minimally invasive spine surgery. They noted that
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risk-adjusted/complication-based thresholds may protect against bias from early case selection during learning, which may skew complication rates because surgeons may select simpler cases when learning a new technique. In a review article, McNamee et al 2 described that a majority of studies used a purely time-based threshold. Another point of importance is the complexity and selection of patients for learning curves. Less experienced surgeons follow a surgical learning curve for the first 2 years of learning a surgery and eventually reach competency similar to that of more experienced surgeons, which was not shown for more complex surgeries, as described by Ferguson et al.13 When technology changes, learning curves can take multiple pathways. When robotic surgery was compared to conventional manual surgery in total knee arthroplasty (TKA), Zhang et al14 found the percentage of cases in which limb alignment differed from preoperative planning by 3° or less was higher with robot-assisted TKA (77.97%) than with conventional TKA (47.19%). Benech et al15 used robotic-assisted navigation to assess whether operative time and pedicle screw accuracy improved with more experience. For pedicle screw accuracy, the first group represented a surgical performance baseline leading up to the investigating surgeon’s 200th robotic-assisted navigation case. The subsequent 2 groups were selected beyond the 200th case, with an average of 15 cases between groups. Operative time significantly decreased from group 1 (175.9 ± 58.2 minutes) to group 2 (135.8 ± 23.9 minutes) (p = 0.013) with a nonsignificant decrease
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to group 3 (121.5 ± 32.3 minutes). Accuracy also significantly increased across groups (group 1: 87%, group 2: 94%, group 3: 98%; p = 0.024). Furthermore, haptic feedback systems have been integrated into minimally invasive and robotic surgery platforms. Tzolov et al16 demonstrated that this advancement enhances the surgeon’s ability to perform delicate maneuvers, increases force, shortens the learning curve for new surgeons, and improves surgical outcomes. They enrolled 57 medical students and assigned them to 2 groups: half in training (n = 29) and half not (n = 28). General visuospatial skills were measured, and different feedback was given. Real-time haptic feedback was rated as more useful, particularly when there was no visual delay. A 2022 study by Feng et al17 demonstrated the learning curve for junior surgeons with this technolog y. For spine surger y, the slope of the learning curve was lower in the robotic-assisted group than in the freehand group. The screw accuracy in the robot-assisted group was superior to that in the freehand group, especially in the upper thoracic region (89.4% vs 76.7%, p < 0.001).
Riding the Curve Structured learning pathways can help overcome the learning curve. These include cadaver labs, simulation-based training, mentorship, and a fellowship. Jajja et al18 stated that a cadaveric skills course is a viable adjunct to clinical experience and improves resident and attending confidence in trainee operative skill. Eighty one percent
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EDITORIAL
of attending surgeons agreed that this positively influenced the granting of autonomy. Wang et al19 found that, in pedicle screw fixation training for spine surgery, pointof-view video-assisted debriefing produced significantly higher post-debriefing technical skill scores than traditional verbal debriefing alone (37 ± 9.7 vs. 25 ± 8.5, p < 0.001). Pattni et al 20 highlighted the importance of video-based interventions, recommending benchmark video review for lower-level physicians and self-video review for more experienced physicians. Schoenfeld et al 21 reported volume-based cut-points for surgeons: 25 for decompressions, 40 for discectomy, 43 for interbody fusion, and 35 for posterolateral fusions. Below these thresholds, there was a 63% increase in the risk of complications following decompressions, a 56% increase following discectomy, a 15% increase following lumbar interbody fusions, and a 47% increase following posterolateral fusions.
Current State and Looking Ahead Despite a rapidly expanding body of learning-curve literature in spine surgery, several translational barriers limit the field’s ability to provide generalizable and clinically actionable conclusions. First is the absence of standardized definitions and metrics across studies. The methods and definition of success varied widely, with most studies relying on operative time as the primary indicator of proficiency. 2 Spine-specific arguments suggest that true mastery must be indexed to patient-reported outcome measures rather than just task-efficiency measures. 22,23
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These issues are worsened by the publication bias of retrospective, single-surgeon series from high-volume centers, and complication rates are likely underestimated because surgeons preferent ia lly select lower-risk patients during their early experience.12,23 Therefore any progress in this field will require a methodological reorientation toward prospective, multicenter, risk-adjusted designs with consistent pre-defined outcomes. CUSUM analysis remains a valuable tool, but its most common retrospective form is usually misapplied and misinterpreted, and decision rules and performance metrics end up poorly specified. 24 Learning-curve CUSUM and risk-adjusted CUSUM, which integrate case complex it y and mitigate bias from nonrandom early case selection, provides a more rigorous alternative now applied to spine cohorts in the literature.25 Given the rapid integration of artificial intelligence and machine learning into clinical practice, dynamically modeling individual learning curves may be more clinically relevant than aggregate learning curves. With intraoperative video analysis and clinical outcomes data, we may begin to see a continuous and personalized assessment of surgeon proficiency in the operating room.26
Conclusion The learning curve in spine surgery is a real, quantifiable, and technolog y-dependent phenomenon, with case-number thresholds varying significantly and with modifiable duration. However, the heterogeneity of the literature’s methodology in reporting data limits the comparability across the litera-
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ture. As a result, the numbered benchmarks should be interpreted as approximations for reference points rather than generalizable thresholds. This field would benefit from standardized reporting metrics and pro-
spective multicenter designs to enable more reliable comparisons and to better inform training, credentialing, and patient safety during the adoption of new surgical spine technologies. l
References 1. Subramonian K, Muir G. The “learning curve” in surgery: what is it, how do we measure it and can we influence it? BJU Int. 2004;93(9):1173-1174. 2. McNamee C, Keraidi S, McDonnell J, et al. Learning curve analyses in spine surgery: a systematic simulation-based critique of methodologies. Spine J. 2024;24(10):1789-1810. 3. Yılmaz E, Emengen A, Gökbel A, et al. Cumulative sum and risk-adjusted cumulative sum analysis of the first-year learning curve for unilateral biportal endoscopy in a neurosurgeon with endoscopic skull base experience. World Neurosurg. 2025;204:124523. 4. Poelman MD, Boeykens A, Harhangi BS, Schröder ML, Staartjes VE. Operative time, recurrence, and complications throughout the initial learning curve in transforaminal endoscopic lumbar discectomy. Acta Neurochir (Wien). 2026;168(1):18. 5. Jacob KC, Patel MR, Prabhu MC, et al. Lateral lumbar interbody fusion: single surgeon learning curve. World Neurosurg. 2022;164:e411-e419. 6. Kuemmerli C, Toti JMA, Haak F, et al. Toward a standardization of learning curve assessment in minimally invasive liver surgery. Ann Surg. 2025;281(2):252-264. 7. Chan JP, Olson T, Gabriel B, et al. What is the learning curve for endoscopic spine surgery? A comprehensive systematic review. Spine J. 2026;26(3):438-449. 8. Easthardt M, Zakko P, Jawad A, Lee M, Park D. Biportal endoscopic spine surgery for lumbar laminectomy and diskectomy: postoperative outcomes and surgical learning curve, a single US surgeon’s experience. J Am Acad Orthop Surg Glob Res Rev. 2024;8(8):e23.00161. 9. McNamee C, Kelly D, McDonnell JM, et al. The learning curve of robotic
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assisted pedicle screw placement: individual patient data meta-analysis. Spine J. 2026;26(1):180-188. 10. Butler AJ, Colman MW, Lynch J, Phillips FM. Augmented reality in minimally invasive spine surgery: early efficiency and complications of percutaneous pedicle screw instrumentation. Spine J. 2023;23(1):27-33. 11. Van Workum F, Stenstra MHBC, Berkelmans GHK, et al. Learning curve and associated morbidity of minimally invasive esophagectomy: a retrospective multicenter study. Ann Surg. 2019;269(1):88-94. 12. Sclafani JA, Kim CW. Complications associated with the initial learning curve of minimally invasive spine surgery: a systematic review. Clin Orthop. 2014;472(6):1711-1717. 13. Ferguson DP, Stevens MT, Stewart SA, Oxner WM, Dunning CE, Glennie RA. Describing the spine surgery learning curve during the first two years of independent practice. Medicine (Baltimore). 2021;100(41):e27515. 14. Zhang H, Bai X, Wang H, Zhu Z, Li X. Learning curve analysis of robotic-assisted total knee arthroplasty with a Chinese surgical system. J Orthop Surg. 2023;18(1):900. 15. Benech CA, Perez R, Lucyk I, Bucklen BS. Beyond the learning curve of robot-assisted navigation spine surgery: refinement of outcomes with extended experience. Cureus. 2024;16(9):e69007.
18. Jajja MR, Lovasik BP, Kim SC, et al. Can a structured, video-based cadaver curriculum demonstrating proficiency enhance resident operative autonomy? J Surg Educ. 2019;76(6):e152-e160. 19. Wang Y, Zhang X, Tang X, et al. Enhancing pedicle screw fixation training: a novel approach using head-mounted devices for video-assisted debriefing. World Neurosurg. 2025;194:123424. 20. Pattni C, Scaffidi M, Li J, et al. Video-based interventions to improve self-assessment accuracy among physicians: A systematic review. PloS One. 2023;18(7):e0288474. 21. Schoenfeld AJ, Sturgeon DJ, Burns CB, Hunt TJ, Bono CM. Establishing benchmarks for the volume-outcome relationship for common lumbar spine surgical procedures. Spine J. 2018;18(1):22-28. 22. Ahn Y, Lee S, Kim WK, Lee SG. Learning curve for minimally invasive transforaminal lumbar interbody fusion: a systematic review. Eur Spine J. 2022;31(12):3551-3559. 23. Khan N, Abboudi H, Khan MS, Dasgupta P, Ahmed K. Measuring the surgical “learning curve”: methods, variables and competency. BJU Int. 2014;113(3):504-508. 24. Woodall WH, Rakovich G, Steiner SH. An overview and critique of the use of cumulative sum methods with surgical learning curve data. Stat Med. 2021;40(6):1400-1413.
16. Tzolov D, Bereuter JP, Geissler ME, et al. Impact of laparoscopic training, haptic feedback and visual haptic latency on virtual fine motor performance. Sci Rep. 2025;15(1):32480.
25. Egu C, Akil H, Clarke T, et al. How many cases to proficiency? A systematic review of the learning curve in endoscopic lumbar interbody fusion. Eur Spine J. Published online May 27, 2026. doi:10.1007/s00586-026-10056-6
17. Feng F, Chen X, Liu Z, et al. Learning curve of junior surgeons in robot-assisted pedicle screw placement: a comparative cohort study. Eur Spine J. 2024;33(1):314-323.
26. Hashimoto DA, Varas J, Schwartz TA. Practical guide to machine learning and artificial intelligence in surgical education research. JAMA Surg. 2024;159(4):455.
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From DISC Sports and Spine Centers in Newport Beach, California.
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Hybrid Cervical Surgery: “Experimental” or Well-Studied Technique? The use of cervical disc replacement has well established. Qiu et al 8 and expanded significantly over the past deXiong et al 9 have each reported cade, with single-level arthroplasty volfollow-up beyond 6 years after ume in the Medicare population rising hybrid surgery. Both compared more than 1400% between 2009 and 20221 hybrid surgery against multilevel ACDF at t he same cenand national private-payer data showing Brandon P. Hirsch, MD ter. Qiu et al 8 retrospectively a parallel increase in utilization relative to ACDF. 2,3 Hybrid surgery combines Figure. A lateral radiograph depicting a disc arthroplasty above a 3-level ACDF. cer v ical disc arthroplast y (CDA) at a single level with anterior cervical discectomy and fusion (ACDF) at an adjacent level, allowing the treatment for each seg ment to be ta i lored to its specific patholog y (Figure). The technique was first reported in 2009; since then, the literature has grown to i nc lude si ng le-c enter c ohor t s, comparative series against multilevel ACDF, and several meta-analyses.4-7 Recent work has extended follow-up beyond a decade, reported adjacent seg ment degenerat ion (ASD) at 10 years, assembled larger datasets on fusion at the instrumented level, and added radiographic and claims-based outcome data. Several commercial payer policies classify hybrid cervical surgery as experimental or investigational as a rationale for noncoverage.
Clinical Efficacy The effectiveness of hybrid surgery is
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followed 26 patients treated with hybrid surgery and 20 treated with 3-level ACDF for contiguous 3-level disease, enrolled between January 2007 and December 2014 and followed for a mean of 141.85 months, or nearly 12 years. 8 Visual Analog Scale (VAS), Japanese Orthopaedic Association (JOA), and Neck Disabilit y Index (NDI) scores i mproved sig n i f ica nt ly i n bot h groups at 3 days and at final follow-up, with no significant difference between groups at any time point. X iong et al 9 reported 6-year results from an earlier retrospective cohort at the same center in patients with 2-segment disease, comparing 20 hybrid surgery patients with 22 treated by 2-level ACDF. VAS, JOA, and NDI improved in both groups of that cohort as well, again with no significant difference between them. Heider et al10 retrospectively examined 36 patients treated with arthroplast y adjacent to a stand-alone titanium cage, with a minimum of 1 year of follow-up. Mean NDI scores fell from 37.5 to 5.76 in that single-arm series, which had no fusion comparator. Yang et al 6 pooled 17 studies comprising 861 patients and Ragab et al7 pooled 9 studies comprising 394 patients, and both reported comparable NDI, VAS, JOA, and Odom outcomes between hybrid surgery and multilevel ACDF.
Motion Preservation and Cervical Alignment Three single-center series reported radiographic outcomes after hybrid surger y, covering motion at the operated segments and global cervical alignment, with fol-
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low-up ranging from 6 months to nearly 12 years. 8,10,12 Qiu et al 8 found significantly greater C2-C7 ROM and greater ROM at the surgical segments at a mean of 141.85 months in the 26 hybrid surgery patients than in the 20 patients treated by ACDF. Heider et a l 10 fou nd ROM preser ved at the arthroplasty levels while ROM at the fused levels was significantly reduced (p < 0.001) in their 36-patient single-arm series. Nguyen et al 12 found that neither C2-C7 lordosis nor cervical sagittal vertical axis differed between hybrid surgery and ACDF at 6 months. Four systematic reviews with meta-analy si s have mea su red cer v ic a l ra nge of mot ion a f ter hybr id su rger y a nd a f ter multilevel ACDF, the largest of them including 2,355 patients treated with hybrid surgery.11 Across 8 studies comprising 424 patients, Hollyer et al 5 found that C2-C7 range of motion (ROM) was greater after hybrid surgery than after multilevel ACDF by 6 degrees, with adjacent segment ROM lower by 3 degrees cranially and 3 degrees caudally. Ragab et al 7 reviewed 9 studies comprising 394 patients and found C2C7 ROM was signif icant ly greater after hybrid surger y, with significantly lower ROM at both adjacent segments. Yang et a l 6 repor ted similar f indings across 17 studies including 861 patients. Sanchez et al11 included 20 comparative studies, with 59,878 ACDF patients as the comparator, and found preservation of cervical ROM and reduct ion in crania l adjacent segment ROM both favoring hybrid surger y at p < 0.0001.
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Adjacent Segment Degeneration, Arthrodesis, and Reoperation Reoperation after hybrid surgery is typically related to symptomatic ASD at the unfused level or pseudarthrosis at the fused level. Qiu et al 8 found ASD at 10 years in approximately 54% of the 26 patients treated with hybrid surgery compared with 75% of the 20 treated with 3-level ACDF. The reduction in severity reached statistical significance (p < 0.05), while the difference in incidence ex hibited a trend only. ROM correlated negatively with ASD. Xiong et al 9 followed 20 hybrid surgery patients and 22 treated by 2-level ACDF for 6 years. Neither group developed sy mptomatic ASD, alt hough superior adjacent segment mobilit y had increased after fusion and decreased after hybrid surgery. Nguyen et al12 compared 23 hybrid surgery patients with 43 treated by ACDF at 6 months. The disc immediately prox imal to the construct showed a decreased Cobb angle and increased height after hybrid surgery while the ACDF group showed an increased Cobb angle and decreased height at the proximal level (p < 0.001). The four meta-analyses were split on whether retained motion reduces the incidence of ASD. Yang et al,6 pooling 17 studies comprising 861 patients, stated explicitly that hybrid surgery did not reduce the incidence of associated level ASD. Ragab et al7 found no significant difference across the 9 studies in their meta-analysis. Sanchez et al11 found ASD less frequent after hybrid surgery across 20 studies comprising 2,355 hybrid surgery and 59,878 ACDF patients.
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"Reoperation has not been shown to be more frequent after hybrid surgery in claims data, single-surgeon series, or long-term cohort follow-up." This discrepancy is most likely related to the shorter follow-up of the studies contributing to the earlier analyses, as ASD accumulates over time. Li et al13 set out to determine whether an adjacent arthroplasty impairs fusion at the treated level in the largest single-center dataset published to date. The aut hors screened 860 patients and included 376 patients treated between January 2015 and January 2023 in groups consisting of 2-level ACDF (n = 205), fusion with arthroplasty distal (n = 82), and arthroplasty with fusion distal (n = 89). Fusion was defined as a continuous bone bridge on 3-dimensional computed tomography. By 1 year, fusion rates were 91.9% (377 of 410 seg ments) in the 2-level ACDF group, 98.8% in the fusion-arthroplast y group, and 100% in the arthroplasty-fusion group (p = 0.002). Fifteen segments in the ACDF group had developed pseudarthrosis, 12 of them at the distal level. The 2-level ACDF group was significantly older. Solid arthrodesis
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was likewise reported at the fusion levels assessed in patients treated with a standalone cage adjacent to an arthroplasty.10 The criterion used to define solid fusion in that series was not clearly specified. Neck VAS at 3 months was lower in the fusion-arthroplasty group in the Li cohort, which also reported fewer complaints of dizziness during the first year.13 Fusion at the instrumented level therefore proceeds at least as quick ly with an arthroplast y adjacent to it as it does after 2-level ACDF. Reoperation itself was reported as a discrete endpoint in 4 studies. Kim et al,14 in the largest of them, found no increased risk of subsequent surger y after hybrid surger y in a propensity-matched claims cohort of 430 hybrid surgery patients and 2,136 treated by multilevel fusion. At 10 years, secondary surgery occurred in none of the 26 hybrid surgery patients compared with 5.0% of the 20 ACDF patients, a difference that did not reach significance and is consistent with the lower ASD severity in the same cohort. 8 Nguyen et al12 found no significant difference in reoperation bet ween hybrid surger y and ACDF at 6 months. Follow-up in that series did not extend beyond 6 months. Heider et al 10 reported a revision rate of 5.6% (2 of 36 patients) at 12 months in the hybrid surgery cohort, without a fusion comparator arm. The meta-analyses have not reported a discrete reoperation endpoint, reporting adjacent-segment kinematics and complications instead; reoperation was recorded in only 3 of the 20 studies contributing to the largest synthesis. 6,7,11 Kim et al 14 and
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Qiu et al 8 reported reoperation after hybrid surgery at rates no higher than after multilevel ACDF.
Complication Rates Four reports addressed complications after hybrid surger y—1 was a single-surgeon series and 3 were meta-analyses. Nguyen et al12 reported less dysphagia at 6 months after hybrid surgery than after ACDF in a single-surgeon series of 66 patients (8.7% vs 32.6%, p = 0.04). Twenty-three of those pat ients were t reated w it h hybrid constructs and 43 with ACDF, with the arthroplasty placed at the most cephalad level. Complications were more common in the ACDF group and returns to the emergency department more common in the hybrid surgery group, but neither difference was significant. Radiographic follow-up extended to 6 months and patient-reported outcomes were not collected. Sanchez et al 11 reported lower dysphagia rates after hybrid surgery in the 2,355 hybrid surgery patients included across 20 studies. Ragab et al 7 found no significant difference in blood loss, operative time, or complication rate in the 394 patients from 9 studies, while Yang et al 6 found blood loss reduced after hybrid surgery in the 861 patients from 17 studies. No study has reported a higher complication rate reaching statistical significance after hybrid surgery compared with after multilevel ACDF. Conclusion Payers continue to classify hybrid cervical constructs as experimental or investigation-
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al. However, clinical results have been reported for 17 years, with consistent findings across independent centers.4,8,10,12,13 Cohorts have been followed beyond a decade. The largest meta-analysis included 861 patients6 and the largest single-center series included 376.13 The literature is predominantly observational. No analysis has identified a safety signal specific to the construct. Complication rates, blood loss, and operative time have been comparable to those of multilevel ACDF across the meta-analyses, 5-7,11 and subsequent surgery rates are
13
indistinguishable from those of multilevel fusion in matched American claims data.14 Fusion at the treated level occurs earlier and more completely than after 2-level ACDF, and clinical outcomes remain equivalent to multilevel ACDF out to nearly 12 years. Reoperation has not been shown to be more frequent after hybrid surgery in claims data, single-surgeon series, or long-term cohort follow-up. The depth and breadth of this body of literature span over 3,000 patients followed for more than 10 years, making the technique far from experimental. l
References 1. Mastrokostas PG, Mastrokostas LE, Razi A, et al. Trends in cervical disk arthroplasty utilization in the Medicare population: projections through 2040. J Am Acad Orthop Surg. 2026;34(4):e573-e580. 2. Witiw CD, Smieliauskas F, Ham SA, Traynelis VC. Cervical disc replacement: examining “real-world” utilization of an emerging technology. J Neurosurg Spine. 2020;32(5):689-695. 3. Gordon AM, Golub IJ, Ng MK, Lam AW, Houten JK, Saleh A. Primary and revision cervical disc arthroplasty from 20102020: patient demographics, utilization trends, and health care reimbursements. World Neurosurg. 2022;168:e344-e349. 4. Barbagallo GMV, Assietti R, Corbino L, et al. Early results and review of the literature of a novel hybrid surgical technique combining cervical arthrodesis and disc arthroplasty for treating multilevel degenerative disc disease: opposite or complementary techniques? Eur Spine J. 2009;18(suppl 1):29-39. 5. Hollyer MA, Gill EC, Ayis S, Demetriades AK. The safety and efficacy of hybrid surgery for multilevel cervical degenerative disc disease versus anterior cervical discectomy and fusion or cervical disc arthroplasty: a systematic review and meta-analysis. Acta Neurochir. 2020;162(2):289-303.
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6. Yang YD, Zhao H, Chai Y, et al. A comparison study between hybrid surgery and anterior cervical discectomy and fusion for the treatment of multilevel cervical spondylosis. Bone Joint J. 2020;102-B(8):981-996. 7. Ragab AM, Taha MM, Makkia MAM, ElSheikh MO, Ismail AM. Efficacy and safety of hybrid surgery versus anterior cervical discectomy and fusion in multilevel cervical degenerative disc disease: a systematic review and meta-analysis. World Neurosurg. 2025;202:124384. 8. Qiu Z, Xiong Y, Yu X, et al. Comparison of 10-year follow-up result of hybrid surgery and anterior cervical discectomy and fusion for the treatment of contiguous three-level cervical degenerative disc diseases: risk factors for heterotopic ossification. Eur Spine J. 2026;35:1828-1838. 9. Xiong Y, Xu L, Yu X, et al. Comparison of 6-year follow-up result of hybrid surgery and anterior cervical discectomy and fusion for the treatment of contiguous two-segment cervical degenerative disc diseases. Spine (Phila Pa 1976). 2018;43(20):1418-1425.
10. Heider FC, Kamenova M, Wanke-Jellinek L, Siepe CJ. Could the different surgical goals of fusion and non-fusion also be achieved in combination within the same patient? Clinical and radiological outcome of hybrid cervical spine surgery. Eur Spine J. Published online 2024. 11. Sanchez MM, Teo THL, Dinesh SK, et al. Comparative outcomes of anterior cervical discectomy and fusion vs hybrid surgery in multilevel cervical degenerative disc disease: a systematic review and meta-analysis. Int J Spine Surg. Published online 2026. 12. Nguyen AV, Gearhart SA, Gonzalez SC, Huang JH, Cooper JK. Short-term radiographic outcomes and early safety of anterior cervical hybrid arthroplasty-fusion versus fusion constructs: a single-surgeon analysis. Neurosurg Focus. 2026;61(1):E9. 13. Li J, Wu Y, Liu H, et al. Does two-level hybrid surgery promote early fusion compared with two-level anterior cervical discectomy and fusion? Spine J. 2025;25(6):1167-1177. 14. Kim KD, Coric D, Khachatryan A, et al. A real-world analysis of hybrid CDA and ACDF compared to multilevel ACDF. BMC Musculoskelet Disord. 2023;24:191.
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Matthew H. Meade, DO
Intraoperative Neuromonitoring in Cervical Myelopathy: Are We Using It or Just Ordering It?
Intraoperative neuromonitoring (IONM) has become an available adjunct during cervical spine surgery, particularly for patients F. James Powlan, MD with degenerative cervical myelopathy (DCM). Its utilization varies considerably among surgeons, institutions, and procedures. Some surgeons routinely employ multimodal monitoring, others reserve it for selected higher-risk cases, and others perform cervical Sam Pourarbab, BS decompression without IONM regardless of underlying pathology. For surgeons who utilize monitoring, the decision is typically made before the patient enters the operating room with plans for motor-evoked potentials (MEPs), Arash Sayari, MD somatosensory-evoked potentials (SSEPs), and electromyography (EMG). Yet, despite its increasing utilization, the extent to which IONM improves neurologic safety during DCM surgery remains incompletely defined. Neuromonitoring does not decompress the spinal cord, maintain spinal cord perfusion, reposition the neck, remove a malpositoned screw, or reverse excessive distraction. The potential value of IONM therefore depends
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From the Department of Orthopaedic Surgery at Rush University Medical Center in Chicago, Illinois.
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in part on whether it provides interpretable information capable of influencing intraoperative management. This distinction is paramount in DCM, where the spinal cord may already have limited physiologic reserve. Professional society guidelines have established SSEP and transcranial MEP (TceMEPs) monitoring as effective for predicting increased risk of severe postoperative neurologic deficits.1,2 However, whether routine monitoring prevents postoperative neurologic injury remains considerably harder to prove.3 These data support IONM as a predictive tool but do not establish that monitoring is necessary for every DCM procedure. Its clinical utility may be better understood by examining when monitoring provides actionable information and how these findings should influence intraoperative decision making. After understanding these modalities, surgeons can be better informed on what modalities, if needed at all, should be utilized during surgery.
Understanding the Utility of Individual Monitoring Modalities The rationale for multimodal monitoring is straightforward. SSEPs predominantly interrogate sensory pathways, whereas Tce-
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MEPs assess motor pathways of particular concern during cervical cord decompression. Free-running EMG provides complementary information regarding mechanical nerve root irritation (Table 1). A 2026 analysis of approximately 155,000 patients undergoing DCM surgery demonstrated progressively greater pooled sensitivity from SSEP alone compared to MEP and multimodal monitoring, while specificity remained high across modalities. 3 SSEPs nevertheless remain valuable. Among nearly 8,000 cervical procedures, postoperative neurologic deficits occurred in 16.5% of patients experiencing a significant SSEP change compared with less
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than 1.5% without a change.4 Persistent or irreversible SSEP changes were substantially more predictive of postoperative neurologic injury than reversible changes. Collectively, MEPs and SSEPs provide complementary information when monitoring is selected, rather than establishing a requirement for multimodal IONM in every DCM procedure.
Monitoring Before the Operation Begins When IONM is selected, obtaining signals before and after positioning may provide an additional reference for identifying position-related changes. In patients with severe
Table 1. IONM Modalities in Degenerative Cervical Myelopathy
IONM Primary Modality Neural Target
Pooled Pooled Sensitivity Specificity
Principal Clinical Utility
Key Limitation
SSEP
Dorsal column (sensory) pathways
~33%
~99%
Continuous surveillance of sensory pathway integrity; may identify compromise during positioning or surgery
Low sensitivity limits detection of isolated motor pathway injury
TceMEP
Corticospinal (motor) pathways
~61%
~95%
Detection of acute motor pathway compromise during decompression, correction, or instrumentation
Signal acquisition and interpretation may be affected by anesthesia, neuromuscular blockade, hypotension, and baseline neurologic dysfunction
Multimodal IONM
Combined sensory and motor pathways
~76%
~94%
Provides complementary assessment of multiple neural pathways and the highest pooled sensitivity among monitoring strategies
Improved diagnostic performance has not established improved postoperative neurologic outcomes
Freerunning EMG
Individual nerve roots
NR
NR
Detection of mechanical nerve root irritation; complementary to evokedpotential monitoring
Limited ability to detect spinal cord injury or predict delayed postoperative root palsy
Sensitivity and specificity values are derived from the 2026 systematic review and meta-analysis of 44 studies including 154,972 patients undergoing surgery for DCM.3 Abbreviations: DCM, degenerative cervical myelopathy; EMG, electromyography; IONM, intraoperative neuromonitoring; SSEP, somatosensory evoked potential; TceMEP, transcranial electrical motor evoked potential NR, not reported.
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cervical stenosis, neck manipulation or excessive upper-extremity traction may contribute to cord, brachial plexus, or peripheral nerve compromise. However, the decision to obtain prepositioning signals is not uniform, and monitoring itself is also not universally employed for all DCM interventions. If prepositioning signals are obtained and an MEP is absent following positioning but was present beforehand, positioning may represent one potential explanation, prompting evaluation of cervical alignment, extremity positioning, blood pressure, anesthetic factors and other potential causes. Patients with DCM, particularly those with myelomalacia, may be challenging to monitor because the underlying myelopathy can degrade baseline electrophysiologic signals. Preoperative studies have demonstrated abnormal central motor conduction in 92% and abnormal SSEPs in 75.5% of patients with DCM, with abnormalities correlating with myelopathy severity. 5 Some patients may therefore require modification of even low-dose volatile anesthesia to obtain adequate TceMEPs.6 Importantly, an absent or unreliable baseline does not itself establish that surgery cannot safely proceed. Rather, if monitoring is being relied upon, it limits the ability of subsequent waveform changes to inform intraoperative decision-making. A difficult decision sometimes needs to be made by the surgeon if there are no baseline signals. The question of neurological injury after injury but before positioning could be a possibility or before damage to the spinal cord owing to the pathology has be considered. If monitoring is not reliable, the “safety” aspect
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of alerting the surgeon of potential dangers also are removed. This decision is multifactorial and based on the surgeon’s expertise and comfort.
Assessing the Reliability of IONM Signals The clinical utility of IONM relies on accurate interpretation of data and signals. MEPs can change because of hypotension, positioning, anesthesia, neuromuscular blockade, or technical factors in addition to obvious surgical injury. With regards to anesthetics, studies have demonstrated baseline MEPs monitorable in nearly 90% of patients under total intravenous anesthesia compared with less than 60% under balanced anesthesia.7,8 A meaningful signal change must also be distinguished from normal waveform variability, and commonly utilized alert criteria differ by modality. For SSEPs, a >50% decrease in amplitude and/or >10% increase in latency from baseline is commonly considered significant. For TceMEPs, amplitude reduction or complete signal loss is generally more informative than latency because MEP latency and morphology are inherently variable. In one large multicenter DCM study a >70% decrease in amplitude was used as the alert threshold.9 Importantly, these thresholds represent warning criteria rather than definitive evidence of neurologic injury and thus should be interpreted in the context of baseline signal quality and reproducibility if IONM is being utilized. These factors matter because the clinical significance of a signal change depends on the conditions under which it occurs. Non-
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surgical causes should be rapidly excluded, while a reproducible change temporally associated with decompression, distraction, correction, or instrumentation should not be dismissed as an artifact simply because alternative explanations exist. Even commonly applied alert criteria may not perform uniformly across pathology; for example, a >70% TceMEP amplitude reduction demonstrated greater sensitivity in high-risk conditions such as ossification of the posterior longitudinal ligament (OPLL) than in more routine spine procedures.9
Responding to an Intraoperative Alert An IONM alert is not a diagnosis of spinal cord injury. Rather, it indicates a physiologic change whose relationship to the immediately preceding surgical maneuver may provide important insight into its etiology. In a multicenter study of nearly 1,200 DCM procedures, TceMEP alerts occurred most commonly during decompression (63%); the next most common situation was screw insertion (16%).10 Monitoring performance differed by pathology, with greater sensitivity in OPLL than DCM (71% vs 43%).10 When a meaningful alert occurs, troubleshooting should be immediate and coordinated. Technical, physiologic, and surgical causes should be assessed and potentially reversible factors addressed (Table 2). Nearly 60% of alerts were rescued after intervention without postoperative paralysis.10 Although signal recovery may suggest successful correction of a reversible process, it cannot establish that neurologic injury would have occurred without intervention.
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The concept of a false positive alert needs to be recognized as well as possible alterations or maneuvers the surgeon performs to see if the signal returns to baseline. In another study of nearly 450 patients undergoing anterior cervical discectomy and fusion, IONM alerts were the strongest independent predictor of postoperative motor deficit.11 Alerts should therefore be interpreted in the context of the preceding maneuver and response to corrective intervention. However, not every signal change necessarily alters the operative objective, which illustrates a central limitation of IONM. The distinction is particularly relevant during posterior decompression. If a signal change prompts evaluation of reversible causes but does not alter the need for adequate decompression, its practical utility becomes less clear. If the operative course ultimately remains unchanged, the question is not whether IONM detected a physiologic change but whether detecting that change provided meaningful clinical value.
C5 Palsy and the Limitations of IONM C5 palsy demonstrates both the strengths and limitations of IONM. In 235 cervical procedures involving the C4-5 level, TceMEP monitoring demonstrated 100% sensitivity and 99% specificity for acute-onset deltoid weakness, whereas spontaneous EMG demonstrated only 20% sensitivity.12 Appropriate muscles must be monitored; deltoid and biceps recordings provide targeted surveillance that distal recordings cannot.13 Even properly conf ig ured monitoring cannot reliably predict delayed C5 palsy,
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which is more common than acute nerve palsy. Neither TceMEP nor spontaneous EMG predicted delayed-onset weakness in the same series.12 Similarly, among nearly 1,200 DCM procedures, TceMEP sensitivity was 100% for lower-extremit y long-tract deficits but only 40% for acute segmental palsy, including 0% sensitivity in DCM and 66.7% in OPLL.10
Normal signals therefore do not eliminate the risk of C5 palsy. Surgical planning, foraminal anatomy, posterior cord drift, and thoughtful decompression remain important. Prophylactic foraminotomy at C4-5 reduced C5 palsy in one prospective laminoplasty study; however, subsequent literature has been mixed.14,15 Ultimately, monitoring may complement surgical judgment; it does not replace it (Table 2).
Table 2. Interpreting IONM Changes During DCM Surgery
Operative Setting
Potential Etiology of Signal Change
Monitoring Considerations
Potential Intraoperative Response
Positioning
Cervical cord compromise; brachial plexus or peripheral nerve compression
Compare signals before and after final positioning; evaluate whether changes are global or extremityspecific
Reassess cervical alignment and extremity positioning; optimize blood pressure; evaluate anesthetic and technical factors
Decompression
Direct cord manipulation, mechanical compression, or impaired cord perfusion
TceMEP changes may provide particularly relevant information regarding motor pathway compromise; correlate changes with the immediately preceding maneuver
Evaluate reversible causes; a signal change does not necessarily preclude completion of a necessary decompression
Instrumentation
Screw-related neural compromise or mechanical manipulation
Correlate signal change temporally with screw placement or other instrumentation
Reassess instrumentation and trajectory; reverse or revise the preceding maneuver when clinically appropriate
Significant SSEP change
Neurologic versus physiologic, anesthetic, or technical change
Common warning criteria: >50% decrease in amplitude and/or >10% increase in latency from baseline
Confirm reproducibility and technical integrity; evaluate physiologic/ anesthetic contributors and preceding surgical maneuver
Significant TceMEP change
Motor pathway compromise versus physiologic, anesthetic, or technical change
Amplitude reduction or signal loss is emphasized over latency; >70% amplitude reduction is a commonly used threshold
Confirm reproducibility and technical integrity; correlate with physiology and preceding surgical maneuver
Acute C5 motor change
Acute C5 root or segmental motor pathway compromise
Deltoid and biceps TceMEPs provide targeted C5 surveillance; spontaneous EMG may provide complementary information
Evaluate recent manipulation, C4-5 foraminal anatomy, decompression, and other potentially reversible causes
Delayed C5 palsy
Multifactorial; may occur despite preserved intraoperative signals
Neither TceMEP nor spontaneous EMG reliably predicts delayed-onset C5 weakness
Recognize that stable intraoperative signals do not exclude delayed postoperative C5 palsy
Alert thresholds represent commonly utilized criteria rather than absolute evidence of neurologic injury and should be interpreted relative to baseline signal quality and clinical context. Abbreviations: DCM, degenerative cervical myelopathy; EMG, electromyography; IONM, intraoperative neuromonitoring; TceMEP, transcranial electrical motor evoked potential.
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Predictive Is Not the Same as Preventive IONM can provide predictive information, but prediction and prevention are not synonymous. A 2026 DCM-specific analysis found no statistically significant reduction in postoperative neurologic deficits between monitored and unmonitored patients; however, this comparison was based on only 5 studies with low absolute event rates. 3 Potential limitations of routine monitoring also include false-positive alerts, added setup time, and cost. In one prospective series, all 7 motor alerts were classified as false positives because no patient developed postoperative neurologic deterioration.16 Interpretation of false-positive alerts is complicated by intraoperative intervention. When a signal recovers after correction and the patient awakens intact, distinguishing impending injury from a false-positive finding may be impossible. Conversely, a signal may change without materially altering the procedure when completion of the decompression remains necessary. This complicates efforts to establish preventive efficacy using postoperative deficits as the primary outcome. Low neurologic event rates further cloud assessment of the clinical and economic value of routine monitoring. For example, no study has established a number-needed-to-monitor to prevent one permanent neurologic deficit because a significant absolute risk reduction with IONM has not been demonstrated. 3 Although broader spine-surgery analyses suggest that IONM may be cost-effective, its economic value in routine DCM remains uncertain when neurologic events are uncommon and preventive benefit is unproven.17
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Utilization reflects this uncertainty. Among nearly 150,000 US DCM admissions from 2016 to 2022, IONM was used in fewer than 30% of all cases over that period, increasing from 23% to 34%.18 These findings underscore the substantial variation in contemporary IONM utilization. Patients with OPLL, severe or multilevel cord compression/myelomalacia, preoperative motor deficits, and those undergoing complex fusion procedures may represent populations in whom actionable intraoperative signal changes are particularly relevant.10,19 Such characteristics may provide a rationale for selective monitoring, although evidence demonstrating improvement in postoperative neurologic outcomes remains limited.
Defining the Role of IONM in DCM Surgery The role of IONM in DCM surgery should not be defined solely by whether monitoring independently prevents postoperative neurologic injury. IONM does not itself prevent neurologic injury; rather, it provides physiologic information that may facilitate recognition of impending neurologic compromise. Whether that information provides sufficient clinical value to justify monitoring depends on the patient, procedure, surgeon, and likelihood that an alert would meaningfully alter management. The evidence supporting routine monitoring for every DCM operation remains incomplete.3 Contemporary practice therefore includes considerable variation in IONM utilization, ranging from routine monitoring to selective use based on pathology and procedural com-
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plexity to performing cervical decompression without any monitoring. For higher-risk patients and complex cervical procedures, the opportunity to identify neurologic compromise while the underlying cause remains reversible may provide a stronger rationale
for IONM use. Accordingly, IONM is best considered an available adjunct to surgical judgment with its utility ultimately determined by whether the information obtained can meaningfully influence intraoperative management. l
References 1. Legatt AD, Emerson RG, Epstein CM, et al. ACNS guideline: Transcranial electrical stimulation motor evoked potential monitoring. J Clin Neurophysiol. 2016;33(1):42-50. 2. Nuwer MR, Emerson RG, Galloway G, et al. Evidence-based guideline update: intraoperative spinal monitoring with somatosensory and transcranial electrical motor evoked potentials: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Clinical Neurophysiology Society. Neurology. 2012;78(8):585-589. 3. Aghaei MM, Babaie A, Bagherzadeh S, et al. Intraoperative neuromonitoring in degenerative cervical myelopathy surgery: a systematic review and meta-analysis of diagnostic accuracy and postoperative neurological outcomes. Eur Spine J. 2026;35(9):5236-5251. 4. Reddy RP, Chang R, Rosario BP, et al. What is the predictive value of intraoperative somatosensory evoked potential monitoring for postoperative neurological deficit in cervical spine surgery? A meta-analysis. Spine J. 2021;21(4):555-570. 5. Yu D, Chang MC, Jeon I, Kim SW. Diagnostic and prognostic significance of preoperative evoked potential tests in degenerative cervical myelopathy. Spine J. 2024;24(1):87-93. 6. LeClair N, Ejimone M, Lynch D, et al. T2-weighted imaging hyperintensity and transcranial motor-evoked potentials during cervical spine surgery: effects of sevoflurane in 150 consecutive cases. J Neurosurg Anesthesiol. 2024;36(2):150-158. 7. Tamkus AA, Rice KS, Kim HL. Differential rates of false-positive findings
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in transcranial electric motor evoked potential monitoring when using inhalational anesthesia versus total intravenous anesthesia during spine surgeries. Spine J. 2014;14(8):1440-1446.
13. Bose B, Sestokas AK, Schwartz DM. Neurophysiological detection of iatrogenic C-5 nerve deficit during anterior cervical spinal surgery. J Neurosurg Spine. 2007;6(5):381-385.
8. Wilent WB, Tesdahl EA, Trott JT, et al. Impact of inhalational anesthetic agents on the baseline monitorability of motor evoked potentials during spine surgery: a review of 22,755 cervical and lumbar procedures. Spine J. 2021;21(11):1839-1846.
14. Katsumi K, Yamazaki A, Watanabe K, Ohashi M, Shoji H. Can prophylactic bilateral C4/C5 foraminotomy prevent postoperative C5 palsy after open-door laminoplasty? A prospective study. Spine (Phila Pa 1976). 2012;37(9):748-754.
9. Takahashi M, Imagama S, Kobayashi K, et al. Validity of the alarm point in intraoperative neurophysiological monitoring of the spinal cord by the Monitoring Working Group of the Japanese Society for Spine Surgery and Related Research: a prospective multicenter cohort study of 1934 cases. Spine (Phila Pa 1976). 2021;46(20):E1069-E1076.
15. Yamasaki Y, Takeuchi K, Numasawa T, et al. Can prophylactic C4/5 foraminotomy prevent C5 palsy after cervical laminoplasty with and without posterior instrumented fusion with maximal expansion? Eur J Orthop Surg Traumatol. 2021;31(6):1037-1046.
10. Funaba M, Kanchiku T, Yoshida G, et al. Efficacy of intraoperative neuromonitoring using transcranial motor-evoked potentials for degenerative cervical myelopathy: a prospective multicenter study by the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research. Spine (Phila Pa 1976). 2022;47(1):E27-E37. 11. Corazzelli G, Ileyassoff H, Corvino S, et al. Evaluating the predictive value of multimodal intraoperative neuromonitoring in anterior cervical discectomy and fusion: a retrospective cohort study on 442 patients. Eur Spine J. 2025;34(8):3389-3397. 12. Bhalodia VM, Schwartz DM, Sestokas AK, et al. Efficacy of intraoperative monitoring of transcranial electrical stimulation-induced motor evoked potentials and spontaneous electromyography activity to identify acute-versus delayed-onset C-5 nerve root palsy during cervical spine surgery: clinical article. J Neurosurg Spine. 2013;19(4):395-402.
16. Taylor AJ, Combs K, Kay RD, Bryman J, Tye EY, Rolfe K. Combined motor and sensory intraoperative neuromonitoring for cervical spondylotic myelopathy surgery causes confusion: a level-1 diagnostic study. Spine (Phila Pa 1976). 2021;46(22):E1185-E1191. 17. Ament JD, Leon A, Kim KD, Johnson JP, Vokshoor A. Intraoperative neuromonitoring in spine surgery: large database analysis of cost-effectiveness. N Am Spine Soc J. 2023;14:100206. 18. Lozano CS, Karthikeyan V, Shakil H, et al. Patient, hospital and geographic factors associated with intraoperative neuromonitoring for cervical spine surgery: a national analysis. Spine (Phila Pa 1976). Published online November 24, 2025. 19. Funaba M, Kanchiku T, Yoshida G, et al. Comparative analysis of fusion and decompression surgery in degenerative cervical myelopathy: a multicenter observational study of transcranial motor-evoked potentials. Spine (Phila Pa 1976). 2026;51(12):861-869.
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From the Department of Orthopaedics at the Hospital for Special Surgery in New York City, New York.
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Expandable Vs Static Interbody Cages: What the Current Evidence Supports Design Rationale Interbody cages restore disc and foraminal height, support segmental lordosis, and transmit load across the disc space until fusion occurs. In a minimally invasive transforaminal approach, the cage reaches the disc space through a corridor bounded by the exiting and traversing nerve roots. A static cage is inserted at its final size, so the corridor limits the height and lordosis it can restore. Serial trialing and impaction through a narrow corridor is the step most often implicated in endplate violation and root retraction injury. Expandable cages were developed to address that limitation.1,2 The implant is inserted collapsed, positioned in the disc space, and then expanded against the endplates in a controlled fashion. The published evidence is more divided than the rapid uptake of these devices suggests. Disc Height and Segmental Lordosis Disc height restoration is the one outcome on which the literature agrees. A meta-analysis of 15 retrospective studies included 2,247 patients, of whom 1,359 received static cages and 888 received expandable cages. The static group showed less improvement in disc height than the expandable group (standardized mean difference −1.90; 95% CI −2.98 to −0.82).
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Nuri Demirci, MD
Foraminal height also improved less in the static group (SMD −3.76; 95% CI −6.33 to −1.19).3 The evidence on segmental lordosis is less consistent. The same meta-analysis detected no Marcos Ojea Quintana, BA difference in segmental lordosis improvement between the static and expandable groups. 3 In a single-institution cohort of 417 patients undergoing single-level TLIF (306 static, 111 expandable), no difference in any lordotic paWilliam Doran, BA rameter was detected at 2 weeks, 6 months, or 1 year.4 Two series report the opposite. Among 148 propensity-matched patients undergoing open 1- or 2-level TLIF, segmental lordosis increased more in the expandable group than in Sheeraz A. Qureshi, the static group at last follow-up MD, MBA (5.7° ± 7.4° versus 1.0° ± 6.1°). 5 Among 210 patients whose TLIF was performed open and with a posterior column osteotomy, the median gain in segmental lordosis was 6.1° with expandable oblique cages and 4.1° with static anterior banana cages.6 In that same series, the gain in total lumbar lordosis was greater in the static group before adjustment (median difference 2.2°; p = 0.031) and greater
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in the expandable group only after propensity matching.6 Across these series, release and preoperative segmental lordosis explain more of the lordotic result than the expansion mechanism does. In the osteotomy series, segments starting below 15° of lordosis gained 3.23° more than segments starting at 25° or above.6 A cage does not generate lordosis across a segment that has not been released.
Subsidence Two meta-analyses published within months of each other reached opposite conclusions. Daher et al pooled 15 studies and found a trend toward lower subsidence in the static group (OR 0.50; 95% CI 0.25–1.00) and a higher reoperation rate in that same group (OR 1.96; 95% CI 1.18–3.25). 3 Shehniamirkhan et al pooled 23 studies covering 1,838 patients and 2,074 fused levels and reported a subsidence rate of 12.8% with expandable cages and 25.7% with static cages.7 Only 3 of those 23 studies compared the 2 cage types directly, and the authors state that their synthesis rests largely on indirect comparison.7 Single-institution comparative series more often show the opposite, though not uniformly. Subsidence occurred in 14.1% of 111 patients with expandable cages and 6.6% of 306 patients with static cages at one academic health system.4 In a 10-year series of 210 TLIF levels, subsidence occurred in 19.7% of 62 expandable levels and 5.4% of 148 static levels.8 In 73 biportal endoscopic TLIF levels performed by a single surgeon, endplate injury on postoperative CT occurred in 18.9% of 37 expandable levels and 2.8% of 36 static levels, and every
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level with an endplate injury subsided.9 One 221-patient series found no difference at 1 year (static 19.7%, expandable 22.4%; p = 0.502).10 The mechanism proposed in these series is the same, and it rests on established endplate biomechanics. Indentation testing across 62 lumbar and sacral endplates showed that the posterolateral regions are stronger and stiffer than the center, and the center of the endplate, where interbody implants are placed, is the weakest part of the lumbar endplate.11 A transforaminal expandable cage passes through that corridor with a small footprint and expands from a central position, so the expansion force is concentrated away from the stronger apophyseal ring. In 148 patients from our center undergoing 1- or 2-level MITLIF with an expandable cage, 22 (14.9%) subsided, and a narrower implant was the significant predictor (p < 0.01).12 In a 252-patient single-level TLIF series (152 static, 100 expandable), the expandable group had more intraoperative subsidence without better perioperative outcomes.13 Endplate preparation and facet release change that risk. In the 10-year series, subsidence occurred in 26.8% of expandable levels treated with unilateral facetectomy alone and 4.8% of expandable levels treated with bilateral posterior column osteotomy.8 Within the endoscopic corridor, results differ by device geometry rather than by approach. In the biportal series,9 the expandable implant was a height-only titanium bullet with a significantly smaller footprint than its static comparators, and it subsided more often. In a unilateral biportal series of 84 patients with degenerative spondylolisthesis (38 static, 46
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expandable), the expandable device had a lordotic profile, and that group had a greater postoperative segmental angle. The fusion advantage at 6 months was no longer present at 1 year, and subsidence was not a study endpoint.14
Surgical Approach and Cage Footprint The lateral literature does not reproduce the transforaminal findings. A prospective series compared 98 consecutive patients undergoing lateral lumbar interbody fusion, with the first 50 receiving static cages and the subsequent 48 receiving expandable cages, so period and learning-curve effects cannot be excluded. Fusion at 12 months was achieved in 94.0% of the expandable group and 82.9% of the static group. Subsidence occurred in 4% of the expandable group and 20% of the static group.15 A meta-analysis of 4 directly comparative lateral studies included 283 patients, 150 with static cages and 133 with expandable cages. That analysis detected no difference in subsidence, disc height, or patient-reported outcomes at 24 months. However, in another analysis, fusion showed a trend in favor of the expandable group (97% of 133 patients) over the static group (92% of 150 patients; p = 0.06).16 The difference between the 2 approaches is footprint. A lateral cage spans the apophyseal ring on both sides, so expansion is distributed across the stronger peripheral endplate.11 A transforaminal cage does not span the ring, so the same expansion loads the weaker center. In the current data, subsidence risk is associated more closely with the approach and the implant width than with the expansion mechanism.
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Bone Quality and Patient Selection Poor bone quality is the most consistently reported patient-level predictor of subsidence. The MRI-based vertebral bone quality (VBQ) score independently predicted subsidence after TLIF in a cohort of 74 patients, with an odds ratio of 1.5 per point (95% CI 1.16–1.97), and was the only independent predictor in that model.17 That cohort was not stratified by cage type, so it identifies a patient risk factor rather than an interaction with the device. In the biportal endoscopic series, the expandable group had higher bone mineral density and lower body mass index than the static group and still subsided more often, which suggests that the device contributed independently of patient factors.9 A VBQ score from the preoperative MRI, or Hounsfield units from the preoperative CT, should be recorded before an expandable cage is planned in an older patient. Cervical Spine and Corpectomy The comparative literature on expandable devices in the cervical spine is smaller. Among 44 patients (77 levels) treated by anterior cervical discectomy and fusion with an expandable titanium cage, cervical lordosis improved from 4.4° to 9.0°, fusion occurred in 69 of 77 levels (89.6%), and subsidence occurred in 16 of 77 segments (20.8%).18 Corpectomy cages are a different device class, and their comparative literature is larger than that for interbody cages. Across 41 cervical studies, the gain in segmental lordosis was 6.72° with expandable cages and 3.69° with static cages. The gain in cervical lordosis was 5.71° and 3.11° respectively. Revisions were
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more frequent in the expandable group at a pooled proportion of 0.06 compared with 0.02 in the static group (p = 0.03).19 Across 26 studies and 1,170 patients, the pooled subsidence rate was 6% for expandable cages and 41% for static cages (p < 0.001). Displacement was more frequent with expandable cages (29%) than with static cages (5%; p < 0.05).20 The static comparator in most of these series is a titanium mesh cage, which subsides for reasons of its own, so that contrast does not transfer to the lumbar comparison. The failure modes also differ from those of interbody cages. An analysis of 373 adverse event reports in the FDA Manufacturer and User Facility Device Experience database found inserter-related problems to be the most common event (34.3%), rarely accompanied by symptoms (5.4%). Endplate subsidence, device migration, and structural fracture were less common and were followed by revision in 80.0%, 77.8%, and 63.8% of reports respectively.21 That database is a voluntary registry without a denominator, so these are proportions of reports rather than rates in patients.
Cost, Graft Volume, and Evidence Quality Recent reviews name the same two limitations. Expandable devices cost substantially more than static devices, and the expansion mechanism occupies volume that would otherwise hold graft.1,13,22 Neither is quantified consistently across the published series. The only published implant price is from a thoracic vertebrectomy series, where an expandable corpectomy cage cost $9,000 and cement cost $75.23 That is a different device and a different
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comparator, so the expandable-versus-static differential itself is still unquantified. No randomized comparison has been reported, and both recent meta-analyses state that every study they included was retrospective.3,7 A systematic review of 49 studies argued that expandable cages should not be treated as one group because rectangular titanium designs with combined medial-lateral and vertical expansion were associated with better patient-reported outcomes than others.22 One series addressed the graft volume limitation directly. In 61 disc spaces treated with an expandable cage together with iliac crest autograft harvested through a minimally invasive technique, bridging bone through the cage was present in 55 (90.2%) on 1-year CT, with no graft-site complication.24 That series was single-arm and did not measure graft volume, so it reports an acceptable fusion rate rather than a solved problem.
Cage Selection in Practice The Table presents a practical comparison of static and expandable interbody devices. The last row of the table represents our practice rather than a finding from the previously mentioned studies. Two rules follow from the data. Release the segment before expecting the cage to correct it, and assess bone quality and the available implant width before choosing a device that concentrates force on the center of the endplate. The Figure shows a representative case. Future Directions Two developments address the failure modes described above. Bi-planar cages expand in
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height and in width, which distributes the expansion force over a larger footprint. A meta-analysis of 15 studies found a higher pooled fusion rate for bi-planar than for uniplanar designs (p = 0.04), with no significant difference in subsidence, and no study compared the 2 designs directly.25 Three-dimensional printed porous titanium reduces stiffness mismatch at the endplate. Across 163 TLIF levels, all of them static banana cages, subsidence of any grade occurred in 5.5% of 73 porous titanium levels and 24.4% of 90 solid titanium levels. Whether that benefit transfers to expandable designs has not been tested. 26
Conclusion Expandable cages restore disc and foraminal height more reliably than static cages, and that gain is largest in the first few months after surgery.3,4 They do not consistently produce more segmental lordosis. Release and cage position explain more of the lordotic result than the device does.3,4,6 In transforaminal fusion, their subsidence risk is at least as high as that of static cages in most single-center comparisons.4,8,9 That risk rises with incomplete release8 and with a narrower implant.12 Poor bone quality predicts subsidence after TLIF regardless of cage type.17 In lateral fusion, where the cage spans the apophyseal ring, the same concern has not been reproduced.15,16 The expandable device is a reasonable default for a collapsed disc space approached through a narrow corridor in a patient with adequate bone. The same device is a poor default in the osteoporotic patient, in whom endplate contact area is the limiting factor. l
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Figure. Two-level transforaminal lumbar interbody fusion with expandable cages at L4–L5 and L5–S1. (A) Preoperative axial (upper) and sagittal (lower) T2-weighted MRI showing disc degeneration with loss of disc height, central and lateral recess stenosis, and no spondylolisthesis. (B) Preoperative standing anteroposterior (upper) and lateral (lower) radiographs. (C) Intraoperative lateral fluoroscopic image after cage placement and pedicle screw fixation, with a cage seated at each level. (D) Standing anteroposterior (upper) and lateral (lower) radiographs at 6 months, showing disc height maintained at both levels.
Table. Practical comparison of static and expandable interbody devices.
Variable
Static Cage
Expandable Cage
Insertion
Serial trialing and impaction; largest feasible footprint
Collapsed insertion with in-situ expansion; less trialing
Disc and foraminal height
Less restoration3
Greater restoration early; the difference was absent at 1 year in one 417-patient cohort3,4
Segmental lordosis
Comparable3,4
Comparable3,4
Subsidence, Lower in most transforaminal single-center comparisons 4,8,9
Higher in most singlecenter comparisons; narrower implants subside more 4,8,9,12
Subsidence, lateral
Higher in one sequential series15
Lower or no difference15,16
Graft volume
Larger chamber
Reduced by the expansion mechanism22
Implant cost
Lower13
Higher1,13
Favored when
Osteoporosis or low VBQ; wide corridor; open approach with posterior column osteotomy
Collapsed disc space; narrow MIS or endoscopic corridor; scarred revision corridor; adequate bone quality
Abbreviations: MIS, minimally invasive surgery; VBQ, vertebral bone quality.
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References 1. Ikwuegbuenyi CA, Willett N, Wang E, et al. Expandable cage technology in minimally invasive transforaminal interbody fusion: where are we and what does the future hold? Expert Rev Med Devices. 2025;22(4):349-360.
10. Ledesma JA, Lambrechts MJ, Dees A, et al. Static versus expandable interbody fusion devices: a comparison of 1-year clinical and radiographic outcomes in minimally invasive transforaminal lumbar interbody fusion. Asian Spine J. 2023;17(1):61-74.
2. Macki M, Hamilton T, Haddad YW, et al. Expandable cage technology: transforaminal, anterior, and lateral lumbar interbody fusion. Oper Neurosurg. 2021;21(Suppl 1):S69-S80.
11. Grant JP, Oxland TR, Dvorak MF. Mapping the structural properties of the lumbosacral vertebral endplates. Spine (Phila Pa 1976). 2001;26(8):889-896.
3. Daher M, Aoun M, Hurley RK, et al. Static versus expandable transforaminal lumbar interbody fusion cages: a meta-analysis of complications, clinical, and radiographic outcomes. Spine J. 2026;26(2):329-340.
12. Subramanian T, Merrill RK, Shahi P, et al. Predictors of subsidence and its clinical impact after expandable cage insertion in minimally invasive transforaminal interbody fusion. Spine (Phila Pa 1976). 2023;48(23):1670-1678.
4. Crawford AM, Striano BM, Bryan MR, et al. Expandable versus static transforaminal lumbar interbody fusion (TLIF) cages: comparing radiographic outcomes and complication profiles. Spine J. 2025;25(2):237-243.
13. Stickley C, Philipp T, Wang E, et al. Expandable cages increase the risk of intraoperative subsidence but do not improve perioperative outcomes in single level transforaminal lumbar interbody fusion. Spine J. 2021;21(1):37-44.
5. Jha R, Chalif JI, Blitz SE, et al. Improved clinical and radiographic outcomes with expandable cages in transforaminal lumbar interbody fusion: a propensity-matched cohort analysis. J Neurosurg Spine. 2025;42(2):147-157.
14. Cao S, Fan B, Song X, et al. Expandable versus static cages in unilateral biportal endoscopy lumbar interbody fusion for treating degenerative lumbar spondylolisthesis: comparison of clinical and radiological results. J Orthop Surg Res. 2023;18(1):505.
6. Ben-Israel D, Park BJ, Berlin C, et al. Segmental lordosis after open transforaminal lumbar interbody fusion using expandable oblique versus static anterior banana cages. Oper Neurosurg. 2026;30(1):78-89. 7. Shehniamirkhan M, Paeinmahali A, Bagherzadeh S, et al. Impact of expandable versus static interbody cages on subsidence and outcomes in minimally invasive transforaminal lumbar interbody fusion: a systematic review and meta-analysis. Global Spine J. Published online June 26, 2026. doi:10.1177/21925682261460800 8. Chang CC, Chou D, Pennicooke B, et al. Long-term radiographic outcomes of expandable versus static cages in transforaminal lumbar interbody fusion. J Neurosurg Spine. 2021;34(3):471-480. 9. Kang TH, Lee G, Kang B, et al. Clinical and radiologic outcomes of expandable versus static cages in biportal endoscopic TLIF: focus on endplate injury and subsidence. J Orthop Surg Res. 2026;21(1):308.
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15. Huo CW, Malham GM, Biddau DT, et al. Lateral lumbar interbody fusion using expandable vs static titanium interbody cages: a prospective cohort study of clinical and radiographic outcomes. Int J Spine Surg. 2023;17(2):265-275. 16. Beyer RS, Shooshani T, Batista B, et al. Static versus expandable cages in minimally invasive lateral lumbar interbody fusion: a systematic review and meta-analysis. Clin Spine Surg. 2025;38(7):326-332. 17. Soliman MAR, Aguirre AO, Kuo CC, et al. Vertebral bone quality score independently predicts cage subsidence following transforaminal lumbar interbody fusion. Spine J. 2022;22(12):2017-2023. 18. Ikwuegbuenyi CA, Ong H, Jitpakdee K, et al. Expandable titanium interbody cage with adjustable height and lordosis for anterior cervical discectomy and fusion: a clinical and radiological study. J Spine Surg. 2025;11(4):893-905.
19. Doherty RJ, Wahood W, Yolcu YU, et al. Determining the difference in clinical and radiologic outcomes between expandable and nonexpandable titanium cages in cervical fusion procedures: a systematic review and meta-analysis. World Neurosurg. 2021;149:249-264.e1. 20. Das AK, Purohit DK, Gupta A, Kataria R. Comparison of radiological and clinical outcomes between expandable and non-expandable cages following cervical corpectomy: a systematic review and meta-analysis. Asian Spine J. 2023;17(3):567-581. 21. Schneider D, Brown EDL, Toscano D, et al. Expandable, but at what cost? Failure patterns in corpectomy cages from 373 real-world adverse events. Spine (Phila Pa 1976). 2026;51(15):1078-1084. 22. Orr D, Anderson R, Jensen A, et al. Expandable interbody cages for lumbar spinal fusion: a systematic review. Spine J. 2025;25(8):1773-1793. 23. Katzir M, Rustagi T, Hatef J, Mendel E. Cost analysis with use of expandable cage or cement in single level thoracic vertebrectomy in metastasis. Global Spine J. 2022;12(5):858-865. 24. Virk S, Vaishnav AS, Sheha E, et al. Combining expandable interbody cage technology with a minimally invasive technique to harvest iliac crest autograft bone to optimize fusion outcomes in minimally invasive transforaminal lumbar interbody fusion surgery. Clin Spine Surg. 2021;34(9):E522-E530. 25. Matsoukas S, Karabacak M, Margetis K. Exploring the differences in radiologic and clinical outcomes of transforaminal lumbar interbody fusion with single- and bi-planar expandable cages: a systematic review and meta-analysis. Neurosurg Rev. 2024;47(1):36. 26. Toop N, Dhaliwal J, Grossbach A, et al. Subsidence rates associated with porous 3D-printed versus solid titanium cages in transforaminal lumbar interbody fusion. Global Spine J. 2024;14(7):1889-1898.
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From the Department of Orthopaedic Surgery at Rush University Medical Center in Chicago, Illinois.
27
Biologic Therapies for Degenerative Disc Disease: Where Do PRP and Cell-Based Therapies Stand in 2026? Degenerative disc disease involves the wear-and-tear processes of the intervertebral disc largely owing to ag ing. 1 Cha nges to t he disc, such as dehydration and morphological loss, can be both asymptomatic and symptomatic. 2 In cases of symptomatic degenerative disc disease, where patients present w it h chronic low back pain, current treatments involve s y mptom ma nagement, phy sic a l therapy, and surger y for persistent functional deficits. 3,4 These options, however, do not address the underlying pathology. The ultimate solution would be to restore the intervertebral disc, and biologics are being investigated to address this treatment gap by providing regenerative solutions to halt disc degeneration 5,6 There are 2 major modalities being investigated and promoted by many clinics today for t hese processes: platelet-r ich plasma (PRP) and cell-based therapies. 7, 8 W h i le ea rly st ud ies have been promising, clinical ev idence is still heterogenous, and recent sham-controlled trials have produced conf licting results. 9–11 The purpose
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Rohit Rajput, BA
of this review is to examine the biological rationale, clinical evidence, limitations, and future directions of PRP and cell-based therapies for degenerative disc disease.
Pathophysiology and Rationale The intervertebral disc is composed of an outer annulus fibrosus surrounding a gelatinous nucleus pulposus containing type II collagen and the proteoglycan aggrecan.12 Aggrecan attracts and retains water, generating hydrostatic pressure that allows the disc to maintain height and resist the daily compressive forces exerted on the spine.13 Aggrecans form complexes with hyaluronic acid and contain negatively charged glycosaminoglycan side chains that attract water, generat ing osmot ic pressu re t hat maintains disc height and load-bearing properties; its chondroitin sulfate components may also inhibit neural ingrowth.14–16 During intervertebral disc degeneration, there is nucleus pulposus cell loss and senescence, which promote inf lammator y signaling through catabolic mediators
Shreya Kurup, BS
Maximillian Y. Lee, BS
Kern Singh, MD
Daniel K. Park, MD
Nathan Lee, MD
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such as interleukin 1β and tumor necrosis factor-α. This signaling increases matrix degradation and reduces type II collagen, aggrecan, and water content. 17–21 These changes contribute to disc height loss, annular fissuring, and neovascularization and nociceptive nerve ingrowth, causing discogenic pain. 22–27 Intrinsic repair is limited owing to the disc’s avascular, hypoxic, acidic, nutrient-poor, and mechanically loaded environment. 28,29 Biologic therapies aim to modif y this degenerative microenvironment. It is hypothesized that PRP provides growth factors with anabolic and anti-inflammatory effects, while mesenchymal stromal and stem cells may promote matrix homeostasis through paracrine and immunomodulatory signaling.6,8,30,31 These therapies are intended not only to reduce pain but to potentially modify the degenerative microenvironment and promote matrix homeostasis, although convincing evidence of structural disc regeneration in humans remains limited.6,8,32
Platelet-Rich Plasma PRP is an autologous blood product processed to contain a concentration of platelets above that of whole blood, along with a mixture of growth factors including platelet-derived grow th factor, transforming growth factor-beta, vascular endothelial growth factor, and epidermal growth factor; reported enrichment varies substantially by protocol, ranging from roughly 2-fold w it h single-spin preparations to 5-fold or more with 2-step centrifugation techniques. 33,34 These growth factors are
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believed to stimulate nucleus pulposus and annulus fibrosus cell proliferation, upregulate type 2 collagen and aggrecan synthesis, and suppress inflammatory mediators such as interleukin 1β and tumor necrosis factor-α in preclinical models. 33 In vivo animal studies have shown that intradiscal PRP can increase disc height and T2 signal intensity on magnetic resonance imaging (MRI) relative to untreated degenerative discs. 33 The first double blind randomized controlled trial (RCT) of intradiscal PRP, conducted by Tuakli-Wosornu et al, assigned 47 patients with chronic discogenic low back pain to receive either PRP (n = 29) or contrast agent (n = 18) and found statistically significant improvements in pain, function, and patient satisfaction in the PRP group at 8 weeks relative to controls, with the improvement in Functional Rating Index maintained at 1 year in the PRP group. 35 A 5- to 9-year follow-up of the same cohort found that 71% of PRP-treated patients maintained clinically meaningful improvements in pain and f unct ion; t he remaining 29% went on to require surgery. 36 A single-arm meta-ana lysis pooling 6 st udies found that pain scores decreased by more than 30% from baseline in approximately 51% to 66% of patients and by more than 50% from baseline in roughly half of patients at 1, 2, and 6 months; ODI scores showed a similar pattern, improving by more than 30% in 40.2% of patients at 2 months and by more t han 50% in 53.9% of pat ients at 6 months, with no significant adverse events reported across included trials. 37
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However, a case of spondylodiscitis with a positive Cutibacterium acnes culture was reported following intradiscal PRP injection, reinforcing the importance of strict sterile technique and risk stratification of patients with elevated infection potential. 38 A prospective cohort study using quantitative MRI found that 79.3% of patients achieved a composite minimally clinically important difference (MCID) in pain and disability at 6 months following intradiscal PRP and that reductions in vertebral marrow fat fraction adjacent to the treated disc were associated with symptom improvement, while whole-disc T2 values remained largely stable over the same period. 39 More broadly, a 2026 systematic review of RCTs across spondylosis found the evidence for intradiscal PRP to be equivocal, with one large trial showing no benefit over saline and smaller trials reporting only modest functional gains, in contrast to more consistent mid-term benefit seen w ith PRP for lu mba r rad ic u lopat hy a nd lu mba r facet pain. 8 Across the broader literature, aggregate success rates at 6 months have been estimated at approximately 55% for intradiscal PRP and 53.5% for intradiscal mesenchy mal stem cell (MSC) therapy, though a worst-case sensitivity analysis accounting for loss to follow-up dropped t he MSC f ig ure to roughly 41%, underscoring how attrition can inf late apparent success rates; systematic reviews consistently classif y the overall quality of this evidence as very low by GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria, reflecting
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small sample sizes, heterogeneous biologic preparation protocols, and a lack of larger placebo-controlled trials.7
Cell-Based Therapies Mesenchymal stem cells can be harvested from bone marrow or adipose tissue and are capable of differentiating along chondrogenic, osteogenic, and adipogenic lineages while also exerting immunomodulator y and paracrine effects that are believed to drive their therapeutic benefit in degenerative disc disease more than direct tissue engraftment. 40 The first in-human pilot study by Orozco et al treated 10 patients with autologous expanded bone marrow MSCs and found rapid improvement in pain and disability, reaching 85% of the event ua l t reat ment ef fect by 3 mont hs along with a significant increase in disc water content on MRI at 12 months despite no change in disc height.41 A subsequent RCT by Noriega et al compared allogeneic bone marrow MSCs to sham injection in 24 patients and found that roughly 40% of
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treated patients were classified as clinical responders, w it h i mproved Pf i r r ma n n grading in the MSC group at 12 months despite no significant difference in disc height or water content between groups; a subsequent long-term follow-up of this same cohort found the improvements in pain, disabilit y, and Pfirrmann grading were sustained through 42 months.41,42 In contrast, the largest allogeneic MSC trial to date, the RESPINE study, randomized 114 patients to a single intradiscal injection of 20 million allogeneic bone marrow MSCs versus sham. The study fell short of its primary endpoint at 12 months, with 74% of the MSC group classified as responders versus 69% of the sham group, a difference that was statistically insignificant.11 Allogeneic mesenchymal precursor cells (MPCs) have shown more consistent results than autologous or allogeneic MSCs, with a multicenter RCT of 100 patients, randomized 3:3:2:2 to 6 million MPCs with hyaluronic acid, 18 million MPCs w it h hyaluronic acid, hyaluronic acid vehicle control, or saline control, demonstrating significant, durable, clinically meaningful improvements in both visual analog scale (VAS) pain and Oswestry Disability Index (ODI) scores in the MPC groups compared with the control arms, sustained through 36 months of follow-up.43 A 2021 systematic review that pooled 3 RCTs of MSC therapy for degenerative disc disease found significant reductions in both VAS and ODI scores versus control, with responder analyses showing MSC-treated patients were roughly 2 times as likely to achieve a minimally
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important or clinically significant change in pain compared with controls.44 Evidence for bone marrow aspirate concentrate and culture-expanded bone marrow MSCs is similarly heterogeneous, as a systematic review of 16 studies and 607 participants found consistent improvement in pain and physical function relative to baseline but rated the overall certaint y of this evidence as very low due to inconsistent methodology, small sample sizes, and poor external validity across studies.45 Finally, the VAST trial tested a viable nucleus pulposus cellular disc allograft, a distinct product class from the MSC suspensions previously discussed, in a multicenter randomized study of 218 patients randomized 3.5:1:1 to allograft, saline, or continued nonsurgical management; both the allograft and saline groups achieved clinically meaningful improvement in VASPI and ODI at 12 months, but a responder analysis showed a clinically meaningful ODI score reduction of at least 15 points in 76.5% of allograft-treated patients versus 56.7% of saline-treated patients, a difference that was statistically significant.46 A subsequent durability analysis of a related nucleus pulposus allograft cohort found a 43% average improvement in back pain severity and a 53% average decrease in ODI score at 24 months, with 64% of patients achieving both the MCID and substantial clinical benefit in pain and 73% achieving the MCID in function.47 Taken together, allogeneic MPCs currently represent the most promising cellbased therapy for degenerative disc disease
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based on indirect comparison across trials rather than any head-to-head study, while two 2025 sham-controlled RCTs (Levi et al for autologous mone marrow aspirate concentrate [BMAC] and Vadala et al for autologous MSCs [the DREAM study]) each failed to show superiority over sham on primar y pain and functional outcomes; it is also worth noting that the larger, later-stage Mesoblast phase III trial built on this same MPC platform did not meet its primar y composite responder endpoint, tempering how far the phase II 36-month data should be extrapolated, though MPC+HA (hyaluronic acid) did significantly reduce mean low back pain versus control at 12 and 24 months, with enhanced effects in the prespecified subgroup with CLBP duration less than 68 months, and 27.8% of MPC+HA baseline opioid users were off opioids at 36 months versus 7.8% of controls. 8,48
Comparative Evidence and Translational Considerations When PRP and stem cell-based therapies are compared directly, the overall pattern favors PRP for extradiscal targets such as lumbar radiculopathy and lumbar facet pain, where randomized trials have shown PRP to match or exceed corticosteroids by 3 to 6 months, while intradiscal applications of both PRP and cell-based therapies have show n more limited and variable efficacy. 8 This discrepancy likely ref lects the biologically unfavorable intradiscal microenvironment, which is characterized by hypoxia, acidosis, and nutrient depriva-
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“Allogeneic MPCs currently represent the most promising cell-based therapy for degenerative disc disease based on indirect comparison across trials, while 2 sham-controlled RCTs each failed to show superiority over sham on primary pain and functional outcomes." tion, conditions that may impair platelet activation, growth factor bioavailability, and MSC survival relative to extradiscal or periarticular injection sites. 8 The 2022 American Society of Pain and Neuroscience (ASPN) evidence-based clinical guideline describes moderate evidence, including 2 relatively small RCTs, supporting intradiscal allogeneic MSCs for discogenic low back pain while rating umbilical cord-derived MSC evidence as low and grading individual supporting studies on a per-study basis rather than issuing a single blanket grade for the category.49 The 2025 American Society of Interventional Pain Physicians (ASIPP) regenerative medicine guideline, the more recent society-level update, reaches a related but distinct conclusion, rating both intradiscal PRP and intradiscal BMAC as Level
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III (Fair) evidence with a moderate consensus-based recommendation, and facet joint PRP/MSC injections and sacroiliac joint PRP injections as Level IV (limited) evidence; the difference between these 2 guidelines partly reflects differing grading frameworks, though the ASIPP guideline itself identifies the scarcity of high-quality studies as its primary limitation, a caveat that ultimately reinforces rather than contradicts the low-certainty framing in the ASPN guideline. 50 Across the pooled evidence base, GRADE assessments consistently rate the certainty of intradiscal regenerat ive t herapy ev idence as ver y low, ref lecting small sample sizes, heterogeneous biologic preparation protocols, inconsistent diagnostic criteria for discogenic pain, and a scarcity of adequately powered, sham-controlled trials.45 Notably, several trials have observed a meaningful placebo or active-comparator effect from intradiscal saline itself, which may obscure t he apparent treatment effect of active biologics and complicate interpretation of "positive" single-arm or non–placebo-controlled studies.46 Among cell-based products, standardized, culture-expanded allogeneic preparations such as MPCs have outperformed minimally manipulated autologous preparations such as BMAC in indirect, crosstrial comparison, suggesting that potency, dose consistency, and manufacturing standardization, rather than cell source alone, may be important determinants of clinical efficacy, though no trial has directly compared MPCs against BM AC head-to-head. 8 A separate small
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trial by Navani et al did directly compare intradiscal PRP against BMC within the same protocol, randomizing 40 patients to saline trigger point injection, PRP, or BMC with crossover; both biologics outperformed placebo, though the trial was underpowered to detect a difference between PRP and BMC themselves. 51 A recurring driver of this heterogeneity is inconsistent patient selection, as trials have varied in their diagnostic criteria for discogenic pain, ranging from provocation discography to imaging-based criteria alone, as well as in Pfirrmann grade thresholds, single- versus multilevel involvement, and exclusion of disc extrusion or Modic changes; more consistent selection criteria across future trials would meaningfully improve comparability.7 It is also worth stating explicitly that, across the RCTs synthesized in the most current systemat ic rev iew of t his literature, adverse events were minimal overall, so the occasional case report of a serious complication such as spondylodiscitis should not be read as representative of the aggregate safety signal. 8
Translational Barriers and Future Directions Despite encouraging early clinical signs, several translational barriers currently limit the clinical adoption of intradiscal PRP and stem cell–based therapies. 8 Foremost is the lack of standardization in biologic preparation, as platelet count, leukocyte content, centrifugation protocol, and activation method can all substantially alter the growth factor profile of PRP, while MSC
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dose, cell source, and manufacturing conditions similarly vary considerably across studies. 8 The hypoxic, acidic, and nutrient-poor intradiscal microenv ironment itself remains a fundamental biological obstacle, as it may limit platelet activation and MSC viability regardless of how the injectate is prepared. 8 Regulatory and cost barriers are equally practical concerns, as whether a given product is regulated as a minimally manipulated 361 HCT/P (human cells, tissues, and cellular and tissue-based product) or requires a full 351 Biologics license materially affects what can be legally marketed, and most of these therapies are not currently covered by commercial insurance, meaning cost disclosure and transparent, Food and Drug Administration–compliant sourcing should be treated as part of informed consent rather than an afterthought. 50 Cell-free strategies such as MSC-derived extracellular vesicles are being explored as a way to deliver the paracrine and immunomodulatory benefits of MSCs while avoiding the survival and safety concerns of live cell transplantation, and bioengineering approaches such as cargo loading, surface modification, and hydrogel-based delivery have shown enhanced retention and efficacy compared with direct extracellular vesicle injection in preclinical models.40 However, this line of research remains confined to preclinical and early translational models, with no completed clinical trials and unresolved questions regarding optimal extracellular vesicle dosing, biodistribution, and durability of effect.40
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Moving forward, larger multicenter randomized trials with standardized biologic preparation, sham controls, and consistent diagnostic criteria for discogenic pain will be essential to determine which patients are most likely to benefit from these therapies.8 Until such trials are available, intradiscal PRP and stem cell–based therapies should be considered investigational options for patients who have exhausted conservative and less invasive interventional measures, rather than as an established substitute for surgical management in appropriately selected candidates.49
Conclusion While PRP and cell-based intradiscal therapies have a coherent biologic rationale for degenerative disc disease treatment, the clinical evidence supporting them is less certain. Early randomized studies of intradiscal platelet rich plasma reported meaningful improvements in pain and function, but larger, sham-controlled trials have not reproduced this finding. This discrepancy likely reflects the lack of standardized preparation protocols and the unfavorable intradiscal microenvironment. Cell-based therapies have demonstrated a similar pattern, with promising early data but then negative primary endpoints in RESPINE and in 2025 sham-controlled trials of autologous BMAC and MSCs. Standardized allogeneic products have worked best, with mesenchymal precursor cells showing benefits through 36 months, though phase III results tempered this finding. Safety has overall been favorable; however, there is always a risk with
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intradiscal administration. Additionally, symptomatic improvement has not been consistent with structural restoration. Clinical efficacy and biologic regeneration should not be conflated; symptomatic improvement
may occur without measurable restoration of disc structure. We encourage standardized patient selection, biologic preparation, and imaging endpoints, alongside adequately powered, multicenter, sham-controlled trials
References 1. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine. 2002;27(23):2631-2644. 2. Kirnaz S, Capadona C, Wong T, et al. Fundamentals of intervertebral disc degeneration. World Neurosurg. 2022;157:264-273. 3. Oichi T, Taniguchi Y, Oshima Y, Tanaka S, Saito T. Pathomechanism of intervertebral disc degeneration. JOR Spine. 2020;3(1):e1076. 4. Maharty DC, Hines SC, Brown RB. Chronic low back pain in adults: evaluation and management. Am Fam Physician. 2024;109(3):233-244. 5. Mizuno S, Vadala G, Kang JD. Biological therapeutic modalities for intervertebral disc diseases: an Orthoregeneration Network (ON) Foundation review. Arthrosc J Arthrosc Relat Surg. 2024;40(3):1019-1030. 6. Bartlett CE, Bansal P, Bhattacharya S, et al. Evolving landscape of regenerative therapies: cell-based and cellfree approaches for chronic low back pain. J Clin Med. 2026;15(13):5235. 7. Schneider BJ, Hunt C, Conger A, et al. The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. Spine J. 2022;22(2):226-237. 8. Zhang RE, Aurangzeb A, Sirisena D. Platelet-rich plasma and stem cell therapies for spondylosis: a systematic review of randomized controlled trials. Eur Spine J. Published online May 16, 2026. doi:10.1007/s00586-026-09997-9
9. Clarke LE, McConnell JC, Sherratt MJ, Derby B, Richardson SM, Hoyland JA. Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition, and micromechanical properties of nucleus pulposus constructs. Arthritis Res Ther. 2014;16(2):R67. 10. Strassburg S, Hodson NW, Hill PI, Richardson SM, Hoyland JA. Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells. PloS One. 2012;7(3):e33739. 11. Pers YM, Soler-Rich R, Vadalà G, et al. Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study). Ann Rheum Dis. 2024;83(11):15721583. doi:10.1136/ard-2024-225771 12. Humzah MD, Soames RW. Human intervertebral disc: structure and function. Anat Rec. 1988;220(4):337-356. 13. Hayes AJ, Benjamin M, Ralphs JR. Extracellular matrix in development of the intervertebral disc. Matrix Biol J. 2001;20(2):107-121. 14. Wei Q, Zhang X, Zhou C, Ren Q, Zhang Y. Roles of large aggregating proteoglycans in human intervertebral disc degeneration. Connect Tissue Res. 2019;60(3):209-218. 15. Daly C, Ghosh P, Jenkin G, Oehme D, Goldschlager T. A review of animal models of intervertebral disc degeneration: pathophysiology, regeneration, and translation to the clinic. BioMed Res Int. 2016;2016:5952165. 16. Sumaya K, Segev D, Mordechai HS, Shilo M, Sharabi M, Sivan SS. Biomimetic glycosaminoglycan analog hydrogels inhibit neurite outgrowth while supporting neuronal cell viability. J Biomed Mater Res A. 2025;113(12):e70009.
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17. Sharma A. The role of adipokines in intervertebral disc degeneration. Med Sci. 2018;6(2):34. 18. Wang DK, Zheng HL, Zhou WS, et al. Mitochondrial dysfunction in oxidative stress-mediated intervertebral disc degeneration. Orthop Surg. 2022;14(8):1569-1582. 19. Calcinotto A, Kohli J, Zagato E, Pellegrini L, Demaria M, Alimonti A. Cellular senescence: aging, cancer, and injury. Physiol Rev. 2019;99(2):1047-1078. 20. Le Maitre CL, Pockert A, Buttle DJ, Freemont AJ, Hoyland JA. Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem Soc Trans. 2007;35(Pt 4):652-655. 21. Zhang F, Zhao X, Shen H, Zhang C. Molecular mechanisms of cell death in intervertebral disc degeneration [review]. Int J Mol Med. 2016;37(6):1439-1448. 22. Feng C, Yang M, Lan M, et al. ROS: crucial intermediators in the pathogenesis of intervertebral disc degeneration. Oxid Med Cell Longev. 2017;2017:5601593. 23. García-Cosamalón J, del Valle ME, Calavia MG, et al. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J Anat. 2010;217(1):1-15. 24. Takahashi K, Aoki Y, Ohtori S. Resolving discogenic pain. Eur Spine J. 2008;17(suppl 4):428-431. 25. Lama P, Le Maitre CL, Harding IJ, Dolan P, Adams MA. Nerves and blood vessels in degenerated intervertebral discs are confined to physically disrupted tissue. J Anat. 2018;233(1):86-97. 26. Stefanakis M, Al-Abbasi M, Harding I, et al. Annulus fissures are mechanically and chemically conducive to the ingrowth of nerves and blood vessels. Spine. 2012;37(22):1883-1891.
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to establish the reproducibility of treatment outcomes. At present, the available evidence does not support routine use of intradiscal PRP or cell-based therapies as established treatment for degenerative disc disease.
27. Jha R, Bernstock JD, Chalif JI, et al. Updates on pathophysiology of discogenic back pain. J Clin Med. 2023;12(21):6907. 28. Urban JPG, Smith S, Fairbank JCT. Nutrition of the intervertebral disc. Spine. 2004;29(23):2700-2709. 29. Hassler O. The human intervertebral disc. A micro-angiographical study on its vascular supply at various ages. Acta Orthop Scand. 1969;40(6):765-772. 30. Yang H, Yuan C, Wu C, et al. The role of TGF-β1/Smad2/3 pathway in platelet-rich plasma in retarding intervertebral disc degeneration. J Cell Mol Med. 2016;20(8):1542-1549. 31. Li P, Zhang R, Zhou Q. Efficacy of platelet-rich plasma in retarding intervertebral disc degeneration: a meta-analysis of animal studies. BioMed Res Int. 2017;2017:7919201. 32. Akeda K, Yamada J, Linn ET, Sudo A, Masuda K. Platelet-rich plasma in the management of chronic low back pain: a critical review. J Pain Res. 2019;12:753-767. 33. Chang Y, Yang M, Ke S, Zhang Y, Xu G, Li Z. Effect of platelet-rich plasma on intervertebral disc degeneration in vivo and in vitro: a critical review. Oxid Med Cell Longev. 2020;2020:8893819. 34. Gruber R. How to explain the beneficial effects of platelet-rich plasma. Periodontol 2000. 2025;97(1):95-103.
These approaches remain investigational, and patients should be counseled regarding the inconsistency of clinical outcomes, uncertain durability, cost, and lack of convincing evidence for true structural disc regeneration. l
37. Peng B, Xu B, Wu W, Du L, Zhang T, Zhang J. Efficacy of intradiscal injection of platelet-rich plasma in the treatment of discogenic low back pain: a single-arm meta-analysis. Medicine (Baltimore). 2023;102(10):e33112. 38. Beatty NR, Lutz C, Boachie-Adjei K, Leynes TA, Lutz C, Lutz G. Spondylodiscitis due to Cutibacterium acnes following lumbosacral intradiscal biologic therapy: a case report. Regen Med. 2019;14(9):823-829. 39. Pan X, Peng G, Yao Q, et al. Intradiscal platelet-rich plasma for discogenic low back pain: a prospective cohort study of early clinical outcomes and quantitative MRI findings. Sci Rep. 2026;16(1):14161. 40. Martins AMV, Pilão S, Santos SG, et al. Bioengineered MSC-derived extracellular vesicles in intervertebral disc therapeutics: A systematic review. Acta Biomater. 2026;218:68-90. 41. Serra-Renom JM, Serra-Mestre JM. Periorbital rejuvenation to improve the negative vector with blepharoplasty and fat grafting in the malar area. Ophthal Plast Reconstr Surg. 2011;27(6):442-446. 42. Noriega DC, Ardura F, Hernández-Ramajo R, et al. Treatment of degenerative disc disease with allogeneic mesenchymal stem cells: long-term follow-up results. Transplantation. 2021;105(2):e25-e27.
35. Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar intradiskal platelet-rich plasma (PRP) injections: a prospective, double-blind, randomized controlled study. PM R. 2016;8(1):1-10.
43. Amirdelfan K, Bae H, McJunkin T, et al. Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized, placebo-controlled 36-month study of safety and efficacy. Spine J. 2021;21(2):212-230.
36. Cheng J, Santiago KA, Nguyen JT, Solomon JL, Lutz GE. Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5-9 years. Regen Med. 2019;14(9):831-840.
44. Xie B, Chen S, Xu Y, et al. Clinical efficacy and safety of human mesenchymal stem cell therapy for degenerative disc disease: a systematic review and meta-analysis of randomized controlled trials. Stem Cells Int. 2021;2021:9149315.
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45. Her YF, Kubrova E, Martinez Alvarez GA, D’Souza RS. The analgesic efficacy of intradiscal injection of bone marrow aspirate concentrate and culture-expanded bone marrow mesenchymal stromal cells in discogenic pain: a systematic review. J Pain Res. 2022;15:3299-3318. 46. Schick F, Pieper CC, Kupczyk P, et al. 1.5 vs 3 Tesla magnetic resonance imaging: a review of favorite clinical applications for both field strengths-part 1. Invest Radiol. 2021;56(11):680-691. 47. Costandi S, Beall DP, Davis TT, et al. Durability of supplemental nucleus pulposus allograft in patients with lumbar discogenic pain. J Pain Res. 2025;18:1901-1908. 48. Beall DP, Bae HW, DePalma MJ, et al. Efficacy and safety of allogeneic mesenchymal precursor cells with and without hyaluronic acid for treatment of chronic low back pain: a prospective, randomized, double blind, concurrent-controlled 36-month study. Spine J. 2025;25(9):1997-2013. 49. Sayed D, Grider J, Strand N, et al. The American Society of Pain and Neuroscience (ASPN) evidence-based clinical guideline of interventional treatments for low back pain. J Pain Res. 2022;15:3729-3832. 50. Manchikanti L, Navani R, Navani A, et al. Comprehensive evidence-based guidelines for regenerative therapies in the management of chronic low back pain: 2025 update from the American Society of Interventional Pain Physicians (ASIPP). Pain Physician. 2025;28(S7):S1-S119. 51. Navani A, Ambach M, Calodney A, et al. The safety and effectiveness of orthobiologic injections for discogenic chronic low back pain: a multicenter prospective, crossover, randomized controlled trial with 12 months follow-up. Pain Physician. 2024;27(1):E65-E77.
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From the Department of Orthopaedic Surgery at the University of California, Davis, in Sacramento, California.
Wound Complications and Management in Thoracolumbar Spine Surgery Ian Singleton, MD
Hai V. Le, MD, MPH
Wyatt D. Vander Voort, MD
Yashar Javidan, MD
Safdar N. Khan, MD
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Thoracolumbar wounds present several challenges. Posterior exposure requires dissection through a large soft-tissue envelope and, in larger cases, can leave substant ia l dead space. This problem is most apparent after long-segment fusion, deformity correction, revision surger y, tumor resection, and sacropelv ic instrumentation. Infection adds additional complexity to treatment; once bacter ia reach t he i mpla nts, biof i l m formation limits the effectiveness of a nt ibiot ics a nd host defenses. At t he s a me t i me, remov i ng t he construct may result in instabilit y or loss of correction, and therefore any treatment plan must consider biof ilm formation and stabilit y as well as account for the remaining soft-tissue envelope.
Classification and Epidemiology Wou nd c ompl ic at ion s fol low i n g thoracolumbar spine surgery can be divided into infectious and noninfectious complications. Noninfectious compl icat ions i nclude persistent drainage, superficial or fascial dehiscence, skin necrosis, seroma, hema-
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toma, and cerebrospinal f luid (CSF) leakage. Each can impair healing and provide a pathway for contamination of the deep surgical site. T he fa sc ia i s t he ke y a natom ic bou nd a r y bet we en a super f ic ia l a nd deep in fect ion. A super f icia l incisional infection is limited to the skin and subcutaneous tissue, while a deep infect ion ex tends t hrough t he t horacolumbar fascia into t he pa raspina l muscu lat u re a nd may involve the instrumentation.1 In addition, the appearance of the sk in can be misleading, and a small area of drainage may communicate with a much larger subfascial collection. Infections occurring within approximately 30 to 90 days are generally considered early. These infections often present with erythema, drainage, dehiscence, fever, or a deep collection. Delayed infections present more than 3 months after surgery and are more likely to involve mature biofilm. The presentation can be subtle, and persistent pain, recurrent drainage, implant loosening, pseudarthrosis, or loss of correction may be the only findings.
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Risk Factors Risk is additive and is generally a combination of multiple factors. In their meta-analysis, Liu et al identified diabetes, obesit y, cor t icosteroid use, prolonged operative time, and increased duration of postoperative drainage as significant risk factors for nonsuperficial infection. 2 Other patient-related factors include malnutrition, smoking, anemia, immunosuppression, and poor functional status. Furthermore, obesity increases wound tension and the volume of relatively hypovascular subcutaneous tissue, while diabetes and perioperative hyperglycemia impair leukocyte function, perfusion, and healing. A malnourished patient may still be obese, so nutritional deficiency should not be excluded by appearance alone. Procedure-related factors include multilevel exposure, revision dissection, prolonged operative time, blood loss, transfusion, instrumentation, and dead space. Prior radiation, multiple incisions, and poorly vascularized scar tissue can also leave few options for closure. Persistent CSF leakage after a durotomy prevents tissue adherence and may lead to dehiscence or infection. Prevention Ef fect ive preoperat ive opt im izat ion is critical for the prevention of wound complications. Glycemic control, nutrition, anemia, tobacco use, and infection at a remote site should be addressed before elective procedures when possible. Patients with prior radiation, multiple procedures,
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severe obesity, or an inadequate soft-tissue envelope may benefit from plastic surgery consultation before the index procedure. Systemic antibiotics should reach an adequate tissue concentration before incision. Dosing should be adjusted for patient weight and repeated during prolonged procedures, after major blood loss, or after approximately 2 drug half-lives. Current guidelines support prophylaxis for less than 24 hours. 3,4 There is no indication to continue prophylaxis beyond 24 hours without an established infection. The presence of a drain does not change this recommendation. 5 Careful surgical technique remains one of the most important preventive measures. Tissue vascularit y should be preser ved during exposure, and prolonged muscle retraction should be released intermittently. Before closure, nonviable tissue should be removed and hemostasis confirmed. Dead space should be eliminated as much as possible. The fascia is then closed securely, followed by a layered closure without excessive tension. Intrawound vancomycin powder has become widely used in posterior spine surgery. A double-blinded randomized trial of 156 patients undergoing posterior lumbar interbody fusion reported surgical site infection rates of 1.3% with intrawound vancomycin and 10.3% with placebo. 6 Although these findings support its efficacy in this setting, the study’s generalizability is limited by the single-center design, the high infection rate in the control group, and the fact that the difference was predominantly attributable to superficial infections. Furthermore, the
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optimal dose and the effects of widespread use on organism selection and antimicrobial resistance remain uncertain. P reoperat ive ch lorhex id i ne bat h i ng and targeted nasal decolonizat ion can be considered when instrumentation is planned.7 Closed-suction drains are reasonable when bleeding or dead space is anticipated, but routine placement has not clearly reduced infection or hematoma. 8 Dilute povidone-iodine irrigation may reduce infection without adversely affecting fusion. 9 Closed-incision negative-pressure therapy is most useful for selected highrisk incisions; the supporting literature remains largely retrospective.10
Clinical Presentation and Diagnosis Increasing pain may be the first symptom of a surgical site infection. Other findings include persistent drainage, er y thema, swelling, f luctuance, skin necrosis, fascial separation, purulence, and exposed instrumentation. Fever and leukocytosis are frequently absent. In a delayed infection, pain, recurrent drainage, loosening, or pseudarthrosis may be the only clues. Staphylococcus aureus remains the most f requent ly isolated orga n ism. Coag ulase-negative staphylococci and Cutibacterium acnes are more typical of indolent implant infection. Gram-negative organisms should be considered in procedures that extend to the sacrum and in patients with substantial healthcare exposure.11 Laboratory evaluation commonly includes a complete blood count, C-reactive protein, and erythrocyte sedimentation rate. The
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trend in C-reactive protein is more useful than a single value. It normally peaks during the first 2 to 3 postoperative days and then declines; persistent elevation or a second increase is concerning for infection.12 Normal inflammatory markers do not exclude the diagnosis. Contrast-enhanced magnetic resonance imaging is generally preferred when a deep collection, epidural extension, discitis, or osteomyelitis is suspected. Immediate postoperative changes and metal artifact can limit interpretation. Computed tomography better demonstrates implant position, loosening, osseous destruction, and gas and can also guide aspiration. Deep-tissue culture remains the diagnostic standard.13 Surface swabs are not reliable. If the patient is stable, antibiotics should be withheld until aspiration or multiple operative specimens are obtained. Blood cultures should be collected first when fever, sepsis, or hematogenous infection is suspected. Antibiotics should not be delayed in patients with hemodynamic instability or progressive neurologic compromise.
Treatment and Management Not every draining wound necessitates a return to the operating room. A short period of low-volume serous or serosanguineous drainage from an otherwise intact incision can be managed with an absorbent dressing and close observation. Swindle et al found that most nonpurulent drainage resolved without surgery and that empiric oral antibiotics did not reduce subsequent debridement or chronic infection.14
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Persistent or increasing drainage is more concerning for infection. The wound should be evaluated for seroma, hematoma, cerebrospinal fluid leakage, fascial separation, and deep infect ion. Pur u lence, fascia l dehiscence, ex posed inst r umentat ion, progressive necrosis, or systemic illness generally requires operative treatment. A superficial abscess should be drained. When the depth cannot be determined, exploration is safer than assuming that the process is superficial. Empiric oral antibiotics should not substitute for imaging, aspiration, or debridement and may suppress subsequent cultures.
Deep Surgical Site Infection The treatment of a deep surgical site infection requires adequate source control, preservation of spinal stability, and a durable closure. Nonviable tissue is excised, deep and epidural collections are evacuated, and multiple cultures are obtained. Loose foreign material and grossly nonviable bone graft should be removed. A second debridement may be necessary when questionable tissue or contamination remains. During an early infection, stable instrumentation is usually retained. Removing the construct before fusion can produce instability or loss of correction. Loose components should be removed or exchanged. Debridement, retention of stable implants, and antibiotic therapy can successfully treat many early infections.15 Delayed infection is more challenging to treat. Implant removal or exchange should be considered when there is a sinus tract,
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Delayed infection is more challenging to treat. Implant removal or exchange should be considered when there is a sinus tract, loosening, pseudarthrosis, hardware failure, recurrent infection, or a failed previous debridement.
loosening, pseudarthrosis, hardware failure, recurrent infection, or a failed previous debridement. If a solid fusion is present, the construct can often be removed, although loss of deformity correction remains possible. An implant-dependent spine requires immediate or staged exchange. Empiric antibiotics are started after deep cultures are obtained. Initial coverage generally includes common gram-positive organisms and methicillin-resistant S. aureus when appropriate. Gram-negative coverage is added based on the clinical setting. Therapy is then narrowed according to culture results. Biofilm-active treatment should be considered for susceptible staphylococcal infection when the implants are retained. Approximately 12 weeks of treatment has commonly been used after debridement and implant retention, although the ideal duration remains uncertain. Tai et al. found no reduction in failure with treatment beyond 12 weeks among patients with adequate
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multiple revisions, extensive tissue loss, exposed dura or instrumentation, substantial dead space, or excessive tension. Paraspinous muscle advancement provides vascularized coverage, fills dead space, and separates the instrumentation from the skin. Houten et al reported fewer infections with prophylactic muscle f lap closure in selected high-risk patients.17 Larger defects may require regional or free-tissue transfer.
Figure. Serial clinical photographs demonstrate the progression of postoperative lumbar wound dehiscence. Peri-incisional erythema and punctate areas of drainage progressed to multiple areas of wound separation and focal central dehiscence (A-D). The wound was surgically debrided and reclosed with interrupted nylon sutures (E). At follow-up, the incision had healed after suture removal (F).
initial source control.16 Duration should therefore reflect the organism, implant status, source control, and clinical response. Chronic suppression is an option when the implants cannot be removed or definitive source control cannot be achieved.
Soft-Tissue Reconstruction Early consultation to plastic surgery is appropriate for wounds with prior radiation,
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Clinical Vignette A 55-year-old man under went an L5-S1 transforaminal lumbar interbody fusion. The initial postoperative course was complicated by postoperative epidural hematoma. As such, urgent operative exploration was performed on postoperative day 2. He subsequently improved and was discharged to a rehabilitation facility. Approximately 6 weeks after the index procedure, he developed drainage and progressive separation of the lumbar incision (Figure). Because the depth of the wound could not be determined clinically, operative exploration was performed. The wound contained fibrinous material and a clear serosanguineous collection consistent with a seroma. There was no gross purulence. The tract extended through the subcutaneous tissue but stopped superficial to the deep fascia. Fluid and multiple tissue specimens were obtained for culture, which subsequently returned Finegoldia magna. Retained nonabsorbable suture was removed, and the subcutaneous tissue and scar were debrided until healthy bleeding tissue was encountered. The deep fascia
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remained intact, and the instrumentation was not exposed. The wound was irrigated with dilute povidone-iodine followed by saline. A closed-suction drain was placed, and the wound was closed in layers to reduce the remaining dead space. Closed-incision negative-pressure wound therapy was subsequently applied. At follow-up, the incision had healed after suture removal.
Conclusion Successful management of thoracolumbar wound complications depends on deter-
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mining the cause and depth of the wound complication. Prevention depends on optimization of modifiable risk factors, appropriate antibiotic prophylaxis, careful tissue handling, hemostasis, elimination of dead space, and a tension-free closure. Stable implants can often be retained during early infection. Delayed infection with loosening, pseudarthrosis, failure, or a sinus tract is more likely to require removal or exchange. Infection control alone is not enough; spinal stability and durable soft-tissue coverage must also be maintained. l
References 1. Centers for Disease Control and Prevention. Surgical Site Infection Event (SSI). In: National Healthcare Safety Network Patient Safety Component Manual. Updated January 2026. Accessed August 31, 2026. https://www.cdc.gov/nhsn/ pdfs/pscmanual/9pscssicurrent.pdf 2. Liu X, Hou Y, Shi H, et al. A meta-analysis of risk factors for non-superficial surgical site infection following spinal surgery. BMC Surg. 2023;23(1):129. 3. Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for Disease Control and Prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152(8):784-791. 4. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. 5. Pivazyan G, Khan Z, Williams JD, et al. Utility of prolonged prophylactic systemic antibiotics for wound drains in posterior spine surgery: a systematic review and meta-analysis. J Neurosurg Spine. 2023;38(5):585-594. 7. Chan AK, Ammanuel SG, Chan AY, et al. Chlorhexidine showers are associated with a reduction in surgical site infection following spine surgery: an analysis of 4266 consecutive surgeries. Neurosurgery. 2019;85(6):817-826.
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8. Schnake KJ, Pumberger M, Rappert D, et al. Closed-suction drainage in thoracolumbar spinal surgery—clinical routine without evidence? A systematic review. Eur Spine J. 2022;31(3):614-622. 9. Egu C, Muscogliati R, Nocun W, et al. RCT-based meta-analysis of povidone-iodine irrigation in spinal surgery: clarifying efficacy and safety. Eur Spine J. 2025;34(10):4670-4679. 6. Han B, Lu H, Pan A, et al. Safety and efficacy of intrawound vancomycin powder in the prevention of lumbar surgical site infection: a prospective, double-blind, randomized controlled study. Int J Surg. 2025;111(1):589-596. 10. Lambrechts MJ, D’Antonio ND, Issa TZ, et al. The usefulness of closed incision negative pressure wound therapy after spinal fusion: a systematic review and meta-analysis. World Neurosurg. 2022;168:258-267.e1. 11. Abdul-Jabbar A, Berven SH, Hu SS, et al. Surgical site infections in spine surgery: identification of microbiologic and surgical characteristics in 239 cases. Spine (Phila Pa 1976). 2013;38(22):E1425-E1431. 12. Kraft CN, Krüger T, Westhoff J, et al. CRP and leukocyte-count after lumbar spine surgery: fusion vs nucleotomy. Acta Orthop. 2011;82(4):489-493.
13. Dowdell J, Brochin R, Kim J, et al. Postoperative spine infection: diagnosis and management. Global Spine J. 2018;8(4 suppl):37S-43S. 14. Swindle JS, Crawford CH III, Byerly LT, Glassman SD, Gum JL, Carreon LY. Management of nonpurulent wound drainage following spinal surgery: is empiric oral antibiotic treatment appropriate? Spine J. 2023;23(11):1575-1579. 15. Dubée V, Lenoir T, Leflon-Guibout V, Briere-Bellier C, Guigui P, Fantin B. Threemonth antibiotic therapy for early-onset postoperative spinal implant infections. Clin Infect Dis. 2012;55(11):1481-1487. 16. Tai DBG, Poehlein E, O’Neil JC, et al. Antibiotic duration after debridement and implant retention for early postoperative spinal implant infections: a multicenter cohort study. Clin Infect Dis. Advance online publication May 5, 2026. 17. Houten JK, Weinstein GR, Collins MJ, Komlos D. Bilateral paraspinal muscle flap closure technique for reduction of wound complications from posterior thoracolumbar spinal fusion: results of a series of 716 patients. J Neurosurg Spine. 2021;34(2):211-217.
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From the Department of Orthopaedic Surgery at the University of California, Irvine, School of Medicine in Costa Mesa, California.
Efficacy of Denosumab: Reducing Fracture Risk and Complications After Surgery Yu-Po Lee, MD
Osteoporosis affects more than 200 million people worldwide.1 The prevalence of osteoporosis is expected to increase in the upcoming years as the global population ages. Osteoporosis is a metabolic disease, characterized by decreased bone density because the amount of bone mass decreases relative to volume, which results in weakening of the bony architecture and ultimately leads to increased bone fragility and fracture risk. These fractures can cause chronic pain, decreased function, reduced quality of life, and shortened life expectancy for patients who have osteoporosis.1 Osteoporosis can affect individuals of all ages and races, but postmenopausal women are especially at risk for developing osteoporosis due to decreased estrogen levels and a resulting increase in osteoclast activity and bone resorption.2 These changes cause a decrease in the amount of bone per unit volume of bone. Once the amount of bone loss has reached a critical level, patients start to develop fractures because the bone cannot support the loads placed on them (Figure). The most common and significant sequelae of osteoporosis is bone fracture. Currently, an estimated 2 million new osteoporotic fractures are diagnosed annually.1 These fractures can be a significant source of pain. But even if the fractures are initially asymptomatic, osteoporotic fractures can lead to pain and disability
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if they cause spinal deformity over time. So, the prevention and treatment of osteoporosis is paramount in order to maintain the quality of life of an aging population.
Pharmacological Treatment The treatment of osteoporosis starts first with making sure patients are taking adequate amounts of calcium and vitamin D. Most sources recommend daily intake of 1000 mg calcium and 600 IU vitamin D for individuals aged 19 to 50 years. 3 For men between the ages of 51 and 70 years, the recommendation changes to 1000 mg calcium and 600 IU vitamin D, while for women between the ages of 51 and 70, it is 1200 mg calcium and 600 IU vitamin D.3 For men and women older than 71, the recommendation is 1200 mg calcium and 800 IU vitamin D.3 After nutritional supplementation, the most common medications prescribed for osteoporosis are bisphosphonates such as alendronate. Bisphosphonates slow down the progression of osteoporosis by binding to the hydroxyapatite crystals in bone and inhibiting the resorption of bone by osteoclasts.4 This slows down bone loss but does not build bone. Denosumab is a monoclonal antibody that works differently from the bisphosphonates. It binds to the receptor activator of nuclear factor-κB ligand (RANKL).5 This prevents the
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Figure. Lateral view of a L2 compression fracture.
RANKL ligand from binding to its receptor counterpart (RANK) on osteoclasts.5 By obstructing RANKL from binding to the RANK receptor on osteoclasts, denosumab blocks osteoclast formation, function, and survival.5
Clinical Data for Denosumab Studies have shown that denosumab is effective in preventing bone loss. Bone et al performed a multicenter, randomized, double-blinded, placebo-controlled study called the FREEDOM trial.6 In this study, 4550 women who received denosumab every 6 months for 3 years were followed for 10 years. The yearly incidence of new vertebral fractures ranged from 0.90% to 1.86% and nonvertebral fractures ranged from 0.84% to 2.55%. Bone mineral density increased by 21.7% in the lumbar spine, 9.2% in the hips, 9.0% in the femoral neck, and 2.7% in the radius. Patients on denosumab had a relatively low rate of fractures after treatment and increased bone density after 10 years. The greatest amount of increase in bone density was in the vertebral bodies. One atypical femoral fracture occurred in the treatment group and the crossover group. Seven cases of osteonecrosis of the jaw were reported in the long-term group and six cases in the crossover group. Thus, patients who take denosumab should be warned about the risk of atypical femur fractures and osteonecrosis of the jaw, and these patients should be monitored for these risks. In another study, Lai et al evaluated 38,906 and 2835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively.7 Patients received denosumab 60 mg subcutaneously every 6 months versus an off-treatment cohort discontinuing denosum-
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ab after 1 dose (which has no known clinical benefit among postmenopausal women). They found that the denosumab treatment group had decreased risk of hip and vertebral body fractures by 38% and 37%, respectively. There are also studies comparing denosumab to bisphosphonates. In a study by Curtis et al, the authors performed a retrospective cohort study to evaluate the efficacy of denosumab versus alendronate in reducing fracture risk in postmenopausal women with osteoporosis.8 Postmenopausal women with osteoporosis were treated with denosumab (n = 89,115) or alendronate (n = 389,536) from 2012 to 2018. Denosumab reduced the risk of hip fractures
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by 36%; nonhip, nonvertebral fractures by 50%; and hip fractures by 30% compared to alendronate. Long-term follow-up also showed that denosumab reduced the risk of major osteoporotic fractures by 9% at 1 year, 12% at 2 years, 18% at 3 years, and 31% at 5 years. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk. In contrast, Pedersen et al performed a randomized clinical trial comparing the efficacy of denosumab (n = 4624) versus alendronate (n = 87,731).9 Within 3 years of follow-up, initiation of denosumab or alendronate was associated with cumulative incidences of 3.7% and 3.1%, respectively, for hip fracture and 9.0% and 9.0%, respectively, for any fracture. The authors concluded that there was no appreciable difference in fracture reduction with denosumab in comparison to alendronate. In another, Li et al performed a meta-analysis of 15 studies with 16,437 patients comparing denosumab with bisphosphonates.10 Compared to the control group (conventional medications), the denosumab group showed no significant difference in increasing total hip bone mineral density, but it significantly improved lumbar spine bone mineral density (p = 0.003). In addition, there were no differences between the 2 groups in terms of reducing osteonecrosis of the jaw or atypical fractures. Some studies have demonstrated a decreased risk of fractures between denosumab and bisphosphonates, and there have also been studies that have shown that patients on denosumab may have improved outcomes after spine surgery. Changsheng et al evaluated 54 patients with osteopenia or osteoporosis who
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had been treated with denosumab and were undergoing a lumbar fusion.11 Patients were divided into 3 groups: denosumab (60 mg subcutaneous injection), bisphosphonates (5 mg zoledronic acid intravenous infusion), and control (no anti-osteoporotic drugs, only calcium + vitamin D). At 6 months, fusion rates were significantly higher in the denosumab (25% complete, 68.6% partial) and bisphosphonate (25% complete, 75% partial) groups compared to the control group (10.5% complete, 57.9% partial, p < 0.001). Hence, there is evidence that patients who have surgery while they are on denosumab will have improved fusion rates and reduced rates of pseudarthrosis.
Dosing There are studies that show that patients who stop denosumab suddenly can have rapid bone loss. Tsourdi et al evaluated the date from phase 2 and 3 clinical trials studying denosumab and noted a rapid decrease of bone mineral density and a steep increase in bone turnover markers after discontinuation of denosumab.12 They also noted that there have been many case reports of multiple vertebral fractures after discontinuation of denosumab. The authors concluded that patients should be evaluated after 5 years of denosumab treatment. Patients considered at high fracture risk should either continue denosumab therapy for up to 10 years or be switched to an alternative treatment. For patients at low risk, a decision to discontinue denosumab could be made after 5 years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover. So, patients who are on denosumab should continue their denosumab
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treatment prior to surgery and continue it for a prolonged period after surgery to avoid an increased risk of fractures or pseudarthrosis. Patients should be evaluated for possible pregnancy before medication initiation. Guidelines also recommend clearance from a dentist and checking vitamin D labs before starting the medication. Serum creatinine, calcium, phosphorus, and magnesium should be monitored over the first few weeks of treatment, and clinicia ns should monitor for hypo- and hypercalcemia after discontinuation. The typical dosing schedule is 60 mg subcutaneously every 6 months.13
Conclusions More studies need to be performed to truly evaluate the efficacy of denosumab. The literature indicates that denosumab is at least as effective as the bisphosphonates in reducing
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fractures. Denosumab may be better than the bisphosphonates in reducing fractures, but that has not been proven conclusively. There are indications that patients who are on denosumab longer will have greater benefits because evidence shows it can increase bone density over time, especially in the vertebral bodies. The risk for jaw osteonecrosis and atypical fractures is similar for patients on denosumab and the bisphosphonates. Thus, patients on denosumab should be warned about the risk of jaw osteonecrosis and atypical fractures. There is also evidence that patients on denosumab may have a decreased risk of pseudarthrosis and a more robust fusion mass. However, more studies are needed to prove this definitively. Patients who are on denosumab should not stop treatment prior to surgery to prevent rapid bone loss that may occur with its discontinuation. l
References 1. Özmen S, Kurt S, Timur HT, et al. Prevalence and risk factors of osteoporosis: a cross-sectional study in a tertiary center. Medicina (Kaunas). 2024;60(12):2109. 2. Lane NE. Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol. 2006;194(2 suppl):S3-S11. 3. Lewiecki EM. Prevention and treatment of postmenopausal osteoporosis. Obstet Gynecol Clin North Am. 2008 Jun;35(2):301-315. 4. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008;83(9):1032-1045. 5. Hanley DA, Adachi JD, Bell A, Brown V. Denosumab: mechanism of action and clinical outcomes. Int J Clin Pract. 2012;66(12):1139-46. 6. Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in post-
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menopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5(7):513-523. 7. Lai EC, Lin TC, Lange JL, et al. Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study. Osteoporos Int. 2022;33(5):1155-1164. 8. Curtis JR, Arora T, Liu Y, et al. Comparative effectiveness of denosumab vs alendronate among postmenopausal women with osteoporosis. J Bone Miner Res. 2024;39(7):826-834. 9. Pedersen AB, Heide-Jørgensen U, Sørensen HT, Prieto-Alhambra D, Ehrenstein V. Comparison of risk of osteoporotic fracture in denosumab vs alendronate treatment within 3 years of initiation. JAMA Netw Open. 2019;2(4):e192416. 10. Li L, Xu J, Ji H, Xia S, Shi F. Efficacy and
safety of denosumab compared with conventional medications in the treatment of osteoporosis: a meta-analysis with trial sequential analysis. Medicine (Baltimore). 2026;105(2):e47150. 11. Changsheng H, Yue L, Wang S, Sun H. Perioperative denosumab versus bisphosphonates for MIDLF surgery in patients with osteopenia: a shortterm prospective cohort study. Global Spine J. 2026;16(2):1102-1112. 12. Tsourdi E, Langdahl B, Cohen-Solal M, et al. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone. 2017;105:11-17. 13. Hildebrand GK, Patel P, Kasi A. Denosumab. [Updated 2024 February 28]. In: StatPearls [Internet]. StatPearls Publishing; 2026. https://www.ncbi. nlm.nih.gov/books/NBK535388/
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Aaryan Patel, BS1
Arush Rao, BS1
Ishan Singhal, MD1
Christopher J. Elia, MD1,2
Daniel K. Fahim, MD1,2
Fall 2026
From the 1Department of Neurosurgery at Corewell Health William Beaumont University Hospital, Oakland University William Beaumont School of Medicine, in Royal Oak, Michigan, and 2Atlas Spine+Brain in Royal Oak, Michigan.
The Intersection of Predictive Machine Learning and Spine Surgery Practice The expansion of artificial intelligence (A I) and machine learning (ML) into healthcare has significantly increased in recent years, and its use in spine surgery has already begun to be investigated and translated into early clinical use. The decision to undergo spine surger y requires consideration of many different factors, such as demographics, comorbid conditions, imaging characteristics, and postoperative courses. ML can evaluate high-dimensional data and complex non-linear relationships, making it well-suited for clinical decision support. Current applications aim to complement clinical judgment, standardize care, and improve risk detection. ML is defined as a group of algorithms that learn from data rather than through a set of predetermined rules. During training, a model receives examples of where the correct outcome is known (for example, complication or no complication). The model starts with a prediction that may be near random. The model prediction is compared to the correct outcome, and the difference (the error)
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is determined. The model adjusts its internal parameters to decrease the size of the error. By repeating this process for each example, the model develops improved predictions of future outcomes and identifies relevant relationships in the data.1-4 The three most common types of AI/ML models in surgical literature include regression, tree-based, and neural network models. The primary advantages of regression models based on logistic regression with regularization are their transparency and interpretability; however, they may have difficulty with nonlinear interactions. Tree-based models, such as Random Forest and Gradient Boosted Trees, provide an advantage for handling non-linearity among variables, and can be effective when dealing with structured clinical data. Models that utilize a neural network architecture can process large amounts of input data, such as medical images, that typically suffer from lack of interpretability. The use of ensemble models is another approach to creating a more stable and accurate AI model by combining several individual AI models.5-7
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Regression models assign weights to input variables such as age, symptom duration, or frailty and combine them into a single continuous prediction. The model “learns” by adjusting those weights, so the predicted outcome gets closer to what happened. Tree-based models work more like a series of clinical decision steps. They repeatedly split patients into groups based on features (for example, “age > 70?” then “smoker?” then “fusion length > 3 levels?”), gradually partitioning patients with similar risk profiles. Many trees can be combined into an accurate ensemble by averaging multiple decision pathways. Neural networks are inspired loosely by brain-like processing and are best thought of as layered pattern detectors. Informat ion passes t hrough multiple layers that progressively identify more complex relationships, and during training, t he net work w ill adjust t housands to millions of internal connections to optimize predictive power. Commonly, model performance is assessed by measuring the area under the receiver operating characteristic cur ve (AUC). Clinically, AUC is considered the probability that a model will place a randomly selected patient w ith an adverse event above a patient who did not experience the adverse event. An AUC of 0.50 is equivalent to chance-level performance, and an AUC of 1.00 is equivalent to perfect discrimination. Important additional performance metrics include sensitivity, specificity, precision, accuracy, and calibration, which assesses how well the model’s predicted risk corresponds to actual events.
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Good discrimination alone does not ensure clinical usefulness; models must also be interpretable, reliable, and implementable in clinical workf lows. 2,8 A list of the most common algorithms, with their advantages and applications, is provided in the Table.
Preoperative Clinical Decision Support in Spine Surgery As of now, most applications of ML in spine surgery are focused on the preoperative phase, specifically focusing on risk stratification and predicting postoperative outcomes. This ref lects both the availability of preoperative data and the importance of surgical candidate selection and shared decision-making. 9,10 R isk st rat if icat ion models at tempt to predict postoperative outcomes, such as complications, hospital length of stay, readmission, and functional improvement, among others. The most common predictive variables have been found to include, but are not limited to, baseline disease severity, symptom duration, age, BMI, smoking status, and paraspinal muscle composition. Specifically, in degenerative disease of the spine, imaging-derived metrics of muscle qua lit y a nd degenerat ion have emerged as strong predictors of postoperative outcomes.11-13 Tree-based models are the most common model categor y used for preoperat ive decision-ma k i ng a nd often outperform traditional regression models. Severa l st udies have included explainability frameworks such as SHAP (Shapley Additive Explanations) to provide transparency to clinicians by explaining
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Table. Common Models for AI/ML in Spine Surgery Research
Name
Model Type
Description
Advantages/ Limitations
Application
Logistic Regression
Linear classifier (regression)
Uses a logistic function to model the probability of a binary outcome from weighted input features; trained by maximizing the likelihood of the data.
Highly interpretable and easy to implement; limited to linear relationships and may underperform on complex datasets
Complication prediction, mortality risk, surgical candidacy modeling
Decision Tree
Tree-based classifier/ regressor
Recursively splits data based on feature thresholds into a tree structure of decision nodes and leaves, yielding simple decision rules.
Easy to interpret and captures nonlinear interactions; prone to overfitting and instability
Risk stratification, patient subgroup classification
Random Forest
Ensemble of decision trees (bagging)
Constructs many decision trees on random subsets of the data and features, then aggregates their votes for a final prediction, improving stability and accuracy.
Handles nonlinearity well and improves accuracy over single trees; reduced interpretability and higher computational cost
Predicting length of stay, complications, discharge disposition
Gradient Boosted Trees (eg, XGBoost)
Ensemble of boosted trees
Trains decision trees sequentially, where each new tree focuses on correcting errors of the previous ensemble, effectively “boosting” predictive performance.
High predictive accuracy and strong performance on tabular data; requires tuning and less transparent
Outcome prediction, risk modeling, radiomic classification
Support Vector Machine (SVM)
Kernel-based classifier
Finds an optimal hyperplane that maximizes the margin between classes; can use kernel functions (e.g., RBF) to handle non-linearly separable data.
Effective in highdimensional spaces; sensitive to parameter choice and less interpretable
Vertebral fracture classification, tumor grading, outcome prediction
Artificial/ Deep Neural Network (ANN/DNN)
Deep learning (fully connected neural network)
Consists of multiple layers of interconnected “neurons” that transform inputs through weighted connections and non-linear activations, learning complex patterns via backpropagation.
Captures complex nonlinear interactions; requires large datasets and lacks interpretability
Predicting functional outcomes, complication risk, survival modeling
Convolutional Neural Network (CNN)
Deep learning (convolutional network)
Specialized neural network for image analysis, using convolutional filters and pooling to automatically learn spatial features (edges, textures, shapes) from images.
Excellent for imaging tasks and real-time analysis; data-hungry, computationally intensive, “black-box” behavior
Disc degeneration detection, stenosis grading, fracture identification, automated segmentation
Recurrent Neural Network/ Long Short-Term Memory (RNN/LSTM)
Deep learning (sequence model)
Neural network designed for sequential data, maintaining an internal state (memory) to capture temporal dependencies; LSTM units address vanishing gradients, enabling learning from longer sequences.
Captures temporal patterns effectively; complex architecture and limited interpretability
Surgical workflow recognition, neuromonitoring interpretation, physiologic deterioration prediction
Bayes Point Machine (BPM)
Probabilistic linear classifier
Bayesian approach to classification that finds the “Bayes point” (an average decision boundary) from all viable linear classifiers in the hypothesis space, approximating the optimal classifier.
Provides calibrated probabilistic outputs; less flexible for complex nonlinear problems
Survival prediction, discharge planning, tumor prognosis modeling
K-means Clustering
Unsupervised learning (clustering algorithm)
Iteratively partitions data into K clusters by minimizing within-cluster variance. Each data point is assigned to the nearest centroid, and centroids are updated until convergence.
Simple and efficient for exploratory analysis; requires pre-set cluster number and assumes simple cluster geometry
Patient phenotyping, degenerative pattern clustering, tumor subgroup discovery
Abbreviations: AI = artificial inteligence; ML = machine learning.
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individual variable contributions to predicted risk.10,14 ML has also been applied to predicting surg ica l ca ndidac y based on t he combinat ion of clinical, demographic, and imaging parameters. The goal of t hese models is to determine which pat ients are most likely to benefit from operative intervention compared with conservative management. The most common model categories utilized for this purpose are logistic regression w ith regularization, tree-based models, and neural networks. Imaging data are commonly analyzed as structured features or directly analyzed through image-based models.15-18 Automated detection, classification, and grading of spinal pathology represent another prominent area of application in the preoperative phase. Deep-learning models, especially convolutional neural networks (CNNs), are well-suited for image analysis. These models have been found to demonstrate strong performance in detecting degenerative changes, disc herniations, spinal stenosis, and alignment of abnormalities. More than half of the studies examining low back pain–related ML applications have focused on detection and diagnosis, with the vast majority employing neural networks.18-20
Intraoperative Assistance and Forecasting Although fewer in number, intraoperative ML applications are rapidly advancing. Ow ing to their abilit y to process image and video data in real time, CNN-based
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architectures are predominant in intraoperative ML applications. 6,19 Automated segmentation and labeling of spinal anatomy represent one of t he most clinically advanced intraoperative ML applications. ML-based segmentation enables rapid identification of vertebrae, neura l elements, and adjacent t issues, which facilitates surgical planning and navigation. Studies have demonstrated that ML-based segmentation can significantly reduce planning time while achieving high accuracy relative to manual segmentation times.12,16 Mixed reality systems using head-mounted displays are an area of active development aiming for improvements in precision a nd reduct ions in cog nit ive work load. Although widespread adoption remains limited, these technologies represent one of the most mature intraoperative ML applications currently available.11 ML models have been developed to predict intraoperative and early postoperative complicat ions. Deep neu ra l net work s, regression-based models, and ensemble models are commonly employed to leverage intraoperative vital signs, laboratory values, operative variables, and administrative claims data. Some systems seek to identify early physiologic deterioration before irreversible damage occurred. 9,17-18 ML classifiers have been used to interpret intraoperative neuromonitoring to differentiate between true neurologic injuries and false positive alerts, as well as predicting impending spinal cord or nerve root injury before permanent damage has occurred.
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Efforts to increase the interpretability of ML models may result in decreased predictive accuracy but are necessary for clinicians to accept such models. Additionally, unresolved issues exist regarding the ethical aspects of data security, patient confidentiality, and responsibility for decisions made using ML models. Developing operating room intelligence systems ut ilizing CNNs and CNN-long short-term memory hybrids to recognize the phases of surgical workf low, predict operative duration, and model surgeon behavior is an emerging area of interest. While these tools are mostly experimental, they w ill likely contribute to enhanced operat ive ef f icienc y in t he coming decades. 5,10-11 ML has also contributed to advances in postoperative recovery monitoring. CNNs have been used to classif y solid fusion versus pseudarthrosis on computed tomography images or radiographs, and in some cases, they incorporate longitudinal imaging over time. Time-series classifiers and wearable devices have been used to continuously monitor gait, activit y, and
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posture, thus allowing clinicians to detect variations from expected recovery courses and extend postoperative care beyond the clinical setting.14,17
Limitations Despite prom isi ng resu lts, sig n i f ica nt barriers limit widespread clinical adoption of ML. Most models are trained on retrospective single-institution datasets collected or limited registries, increasing the likelihood of model overfitting and reducing generalizability. Prospective evaluation of models is rare, and few models have been implemented in actual clinical workflows.1,9-11 Although spine care produces a wide variety of data, much of it exists in the form of unstructured clinical notes or high-dimensional imaging data that are difficult and expensive to analyze and integrate. Most predictive models are based on simple representations of imaging rather t han direct image analysis. Addit ional limitations of predictive models include inconsistent reporting of patient-reported outcomes, such as pain intensity and qualit y of life. Biases contained w ithin historic data may produce predict ions t hat may per pet uate d ispa r it ies i f not properly addressed. 3,11,14 Black-box models, especially complex deep neural networks, may produce accurate predictions without providing a rationale for their predictions. Efforts to increase the interpretability of models may result in decreased predictive accuracy but are necessary for clinicians to accept ML models. Additionally, unresolved issues exist regarding the ethical aspects of
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data security, patient confidentiality, and responsibilit y for decisions made using ML models. 3,10-11
Conclusion ML is being increasingly adopted throughout the continuum of spine surgery care. Analysis of imaging and automated segmentation represents the most clinically mature ML applications. Intraoperative navigation systems demonstrate the most
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dramatic improvements in precision and efficiency afforded by these models. While preoperative risk stratification and postoperative outcome prediction have significant promise, both areas require robust external validation and prospective evaluation before widespread clinical adoption. As data quality increases and validation studies grow in number, ML is expected to significantly benefit contemporary spine surgery practices. l
References 1. Chang M, Canseco JA, Nicholson KJ, Patel N, Vaccaro AR. The role of machine learning in spine surgery: the future is now. Front Surg. 2020;7. 2. Liu Y, Chen PHC, Krause J, Peng L. How to read articles that use machine learning: users’ guides to the medical literature. JAMA. 2019;322(18):1806-1816. 3. Adida S, Legarreta AD, Hudson JS, et al. Machine learning in spine surgery: a narrative review. Neurosurgery. 2024;94(1):53-64. 4. Merali ZG, Witiw CD, Badhiwala JH, Wilson JR, Fehlings MG. Using a machine learning approach to predict outcome after surgery for degenerative cervical myelopathy. PLoS ONE. 2019;14(4):e0215133. 5. Prasanth Romiyo, Ding K, Dejam D, et al. Systematic review and evaluation of predictive modeling algorithms in spinal surgeries. J Neurologic Sci. 2020;420:117184-117184. 6. Wilson B, Gaonkar B, Yoo B, et al. Predicting spinal surgery candidacy from imaging data using machine learning. Neurosurgery. 2021;89(1):116-121. 7. Gengyu H, Jinyue D, Chunjie G, et al. The predictive value of preoperative paraspinal muscle morphometry on complications after lumbar surgery: a systematic review. Eur Spine J. 2022;31(2):364-379. 8. Charles YP, Lamas V, Ntilikina Y. Artificial intelligence and treatment algorithms
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in spine surgery. Orthop Traumatol Surg Res. 2023;109(1 suppl):103456. 9. D. Müller, D. Haschtmann, Fekete TF, et al. Development of a machine-learning based model for predicting multidimensional outcome after surgery for degenerative disorders of the spine. Eur Spine J. 2022;31(8):2125-2136. 10. Yagi M, Yamanouchi K, Fujita N, Funao H, Ebata S. Revolutionizing spinal care: current applications and future directions of artificial intelligence and machine learning. J Clin Med. 2023;12(13):4188. 11. Sumdani H, Aguilar-Salinas P, Avila MJ, Barber SR, Dumont TM. Utility of augmented reality and virtual reality in spine surgery: a systematic review of the literature. World Neurosurg. 2022;161:e8-e17. 12. Scherer M, Kausch L, Ishak B, et al. Development and validation of an automated planning tool for navigated lumbosacral pedicle screws using a convolutional neural network. Spine J. 2022;22(10):1666-1676. 13. Park S, Kim JK, Chang MC, Park JJ, Yang JJ, Lee GW. Assessment of fusion after anterior cervical discectomy and fusion using convolutional neural network algorithm. Spine. 2022;47(23):1645-1650.
15. Boaro A, Azzari A, Basaldella F, et al. Machine learning allows expert level classification of intraoperative motor evoked potentials during neurosurgical procedures. Comput Biol Med. 2024;180:109032. 16. Lahoti Y, Sai S, Ahmed W, et al. Development of a novel machine learning model to automate vertebral column segmentation utilizing biplanar full-body imaging. Spine J. 2025;25(12)2803-2810. 17. Fang L, Pan Y, Zheng H, et al. A study on predicting the efficacy of posterior lumbar interbody fusion surgery using a deep learning radiomics model. Acad Radiol. 2025;32(9):5339-5352. 18. Shahrestani S, Garcia C, Miller AM, et al. Optimizing predictive model performance in adult spinal deformity surgery: a comparative head-to-head analysis of learning models for perioperative complications. Neurosurg FOCUS. 2025;58(6):E12-E12. 19. Zhao P, Zhu S. Advances and challenges in AI-assisted MRI for lumbar disc degeneration detection and classification. Eur Spine J. 2026;35(3):1291-1300. 20. Ali IS, Yianni Bakaes, MacLeod JS, Lee TY, Cho S, Hsu WK. Artificial intelligence in planning for spine surgery. Curr Rev Musculoskelet Med. 2025;18(12):627-634.
14. Schönnagel L, Caffard T, Vu-Han TL, et al. Predicting postoperative outcomes in lumbar spinal fusion: development of a machine learning model. Spine J. 2024;24(2):239-249.
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Takayuki Kobayashi, MD
Mental Workload Stress in Orthopedic and Spine Surgeons
Mental workload has attracted increasing attention across a wide range of fields, including healthcare. With the growing availability of wearable devices such as smartwatches and rings, physiological Jusin Woo, BS parameters such as heart rate and heart rate variability (HRV) can now be monitored continuously during work, exercise, and rest. These technologies have made physiological responses to stress and workload increasingly accessible in everyday life. Ignacio Rocca, BS Despite its intuitive familiarity, however, mental workload is not a simple concept to define.1 It is generally considered a multidimensional construct arising from the interaction between task demands and the individSravisht Iyer, MD ual performing the task. Mental workload may encompass the cognitive resources required to perform a task, the effort and attention devoted to meeting those demands, and the resulting psychological and physiological responses. Accordingly, there remains no universally accepted definition or single measurement that fully captures mental workload.
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From the Department of Orthopaedics at the Hospital for Special Surgery in New York City, New York.
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Surgeons represent a particularly interest ing populat ion in which to study mental workload. 2 In addition to clinical decision-making and communication with patients, surgeons must continuously process large amounts of information and make decisions under time pressure during operative procedures. Unexpected intraoperative events, technical difficulties, and complications may further increase cognitive demands. Excessive cognitive workload may also adversely affect surgical performance, making its assessment relevant not only to surgeon well-being but potentially also to surgical performance and patient safety. In recent years, an increasing number of studies have attempted to quantif y a surgeon's menta l work load using bot h subjective assessment and objective physiological measure. However, mental workload cannot be observed directly, and substantial questions remain regarding what each measurement actually represents, how these measurements should be interpreted, and how reliably they can be obtained in the complex environment of the operating room. In this article, we provide an overview of the fundamental concepts underlying mental workload, current approaches to its measurement and interpretation in surgeons
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and other healthcare professionals, methodological challenges in studying mental workload in clinical settings, and potential future applications of this emerging field.
How Can We Measure the Mental Workload? Mental workload is not a single, directly measurable quantity, and different methods capture different aspects of it. Reviews of surgical workload research have used a wide range of approaches, including subjective ratings, cardiac and electrodermal measures, eye tracking, electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), hormonal measurements, and wearable sensors. 2,3 Subjective ratings prov ide a practical starting point. The NASA task load index (NASA-TLX) asks respondents to rate perceived mental demand, physical demand, temporal demand, performance, effort, and frustration after a task (Figure). Because it is simple to administer and does not interfere with the surgical procedure, it has been widely used in studies of surgeons’workload.4 The Surgery Task Load Index (SURG-TLX) was developed specifically for surgery and incorporates dimensions such as task complexity, situational stress, and distractions.5 These instruments are easy to administer and provide direct information about perceived work load, although their retrospective nature limits their ability to capture changes occurring throughout a procedure. Physiological measures offer the possibility of continuous assessment. Heart rate and
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HRV are among the most commonly used measures and provide information related to autonomic nervous system activity. Respiratory rate and electrodermal activity can provide additional information on physiological arousal. Importantly, many of these signals can now be collected continuously using chest straps, wrist-worn sensors, and other wearable devices, making them particularly attractive for studying workload during surgical procedures. Figure. NASA Task Load Index.
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Other approaches provide different perspectives on the surgeon’s response to cognitive demands. Eye tracking can characterize visual behavior through measures such as gaze patterns and pupil responses, while EEG and f NIRS can provide information related to brain activity.6,7 These methods differ substantially in their complexit y, temporal resolution, and feasibility in the operating room, but together they illustrate the growing range of tools available to invest igate menta l work load. Ta ken together, these methods provide several complementary approaches to assessing different aspects of mental workload.
How Should We Interpret Mental Workload Measurements? The f irst rule is to interpret each measurement according to the phenomenon it actually represents. For example, a high NASA-TLX score ref lects a surgeon’s perceived workload, whereas changes in HRV ref lect changes in autonomic regulation. Neither should be interpreted as a direct measure of mental workload itself. Physiological signals may also be inf luenced by multiple factors related to the surgeon, procedure, and operative environment, as discussed in previous surgical studies. 8–10 Therefore, changes in these measurements should always be interpreted in the context in which they were obtained. The context in which a measurement is obtained is also important for its interpretation. A single high or low value is difficult to interpret in isolation. Measurements become more meaningful when compared
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with an appropriate baseline and considered in relation to surgical context, such as the operative phase, the task being performed, or unexpected intraoperative events.11 To capture mental workload more comprehensively, mu lt i moda l assessment may therefore be valuable. In simulation st ud ies, combi nat ions of c a rd iac a nd ocular features have predicted workload and performance better than individual features,12 while models combining EEG, HRV, electrodermal activity, and motion have also outperformed the single-signal approach.13 Although these findings require further validation in real surgical environments, they illustrate an important principle: mental workload cannot be fully characterized by a single signal. Rather, it should be triangulated from multiple complementary measures, with each interpreted in its appropriate context.
Why Is Mental Workload Difficult to Study in Surgeons? Two major challenges in studying a surgeon's mental workload are artifact and confounding factors. A rt ifacts are measurement errors in which the recorded signal does not accurately represent the underlying physiology. In the operating room, motion can corrupt photoplethysmography signals, electrocautery and power tools may interfere with sensors, and signal dropout may occur because of device positioning or sterile-field constraints. These problems may be mit igated t hrough appropriate sensor placement and improvements in measurement technology.14
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Confounding factors present a different problem: the physiological signal may be measured accurately but may change for reasons unrelated to cognitive demand. Physical exertion, posture, speech, thermal load, emotional arousal, caffeine, medication, and sleep can all influence physiological measures used as proxies for mental workload. 2,15 In addition, substantial day-to-day variability may arise from factors such as prior night call, circadian timing, position in the operative schedule, cumulative case load, or carryover from a previous difficult case.16 Unlike artifacts, many of these influences cannot be eliminated simply by improving the measurement device. Instead, they must be considered in the study design, through appropriate baseline measurements, synchronization with perioperative events. These methodological challenges are further reflected in the considerable heterogeneity of measurement approaches across existing surgical workload studies.2 Ultimately, reliable assessment of mental workload in the operating room depends not only on what we measure, but also on when, where, and under what circumstances we measure it.
Future Perspective Despite these challenges, the ability to quantify mental workload opens several exciting possibilities in surgery. As wearable and sensing technologies continue to evolve, repeated or longitudinal measurements may allow us to understand how surgeons respond and adapt to cognitive demands over time. Such information could provide new insights into both surgeon well-being and the cognitive aspects of surgical
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The ability to quantify mental workload opens several exciting possibilities in surgery. As technologies continue to evolve, longitudinal measurements may
allow us to understand how surgeons respond and adapt to cognitive demands over time.
expertise, potentially revealing changes that cannot be captured by conventional measures of surgical performance alone. Another exciting opportunity lies in the evaluation of emerging surgical technologies. Robotics, navigation, and augmented reality are increasingly changing how surgeons interact with information and perform procedures. Mental workload provides a unique opportunity to evaluate these technologies from the surgeon’s perspective.17,18 While previous studies have primarily relied on subjective measures such as the NASA-TLX,4 multimodal assessment may provide a more comprehensive understanding of how new technologies affect surgeons, not simply whether workload is reduced, what changes, when it changes, and why.19,20 Ultimately, the value of measuring mental workload may lie not in measurement itself, but in what it allows us to understand. As measurement technologies become more accessible and sophisticated, what has tra-
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ditionally been an invisible part of surgery may gradually become something we can observe, understand, and potentially improve.
Conclusion Mental workload in surgeons has received increasing attention alongside advances in measurement technologies, and a wide range of subjective and objective measures have been explored. However, no single standard-
ized approach has yet been established, and each measurement may be inf luenced by multiple factors. Combining complementary measures and interpreting them in the appropriate context will therefore be essential. Despite these challenges, mental workload is an emerging field with the potential to provide new insight into surgical training, surgeon well-being, and the way surgeons work in the future. l
References 1. Longo L, Wickens CD, Hancock G, et al. Human mental workload: a survey and a novel inclusive definition. Front Psychol. 2022;13:883321. 2. Dias RD, Ngo-Howard MC, Boskovski MT, et al. Systematic review of measurement tools to assess surgeons’ intraoperative cognitive workload. Br J Surg. 2018;105:491–501. 3. Almukhtar A, Caddick V, Naik R, et al. Objective assessment of cognitive workload in surgery: a systematic review: A systematic review. Ann Surg. 2025;281:942–951. 4. Süer MS, Demir S, Çanakçı MH, et al. Training laparoscopic surgeons: assessing workload and skill using Nasa-tlx. J Surg Educ. 2025;82:103588. 5. Wilson MR, Poolton JM, Malhotra N, et al. Development and validation of a surgical workload measure: the surgery task load index (SURG-TLX). World J Surg. 2011;35:1961–1969. 6. Leff DR, Elwell CE, Orihuela-Espina F, et al. Changes in prefrontal cortical behaviour depend upon familiarity on a bimanual co-ordination task: an fNIRS study. Neuroimage. 2008;39:805–813. 7. So WKY, Wong SWH, Mak JN, et al. An evaluation of mental workload with frontal EEG. PLoS One. 2017;12:e0174949. 8. The A-F, Reijmerink I, van der Laan M, et al. Heart rate variability as a measure of mental stress in surgery: a systematic review. Int Arch Occup Environ Health. 2020;93:805–821.
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9. Kwon J-W, Sung S, Lee S-B, et al. Intraoperative real-time stress in degenerative lumbar spine surgery: simultaneous analysis of electroencephalography signals and heart rate variability: a pilot study. Spine J. 2020;20:1203–1210. 10. Kwon J-W, Lee S-B, Sung S, et al. Which factors affect the stress of intraoperative orthopedic surgeons by using electroencephalography signals and heart rate variability? Sensors (Basel). 2021;21:4016. 11. Torkamani-Azar M, Lee A, Bednarik R. Methods and measures for mental stress assessment in surgery: A systematic review of 20 years of literature. IEEE J Biomed Health Inform 2022;26:4436–4449. 12. Zakeri Z, Mansfield N, Sunderland C, et al. Physiological correlates of cognitive load in laparoscopic surgery. Sci Rep. 2020;10:12927. 13. Zhou T, Cha JS, Gonzalez G, et al. Multimodal physiological signals for workload prediction in robot-assisted surgery. ACM Trans Hum Robot Interact. 2020;9:1–26. 14. Quigley KS, Gianaros PJ, Norman GJ, et al. Publication guidelines for human heart rate and heart rate variability studies in psychophysiology-Part 1: Physiological underpinnings and foundations of measurement. Psychophysiology. 2024;61:e14604. 15. von Rosenberg W, Chanwimalueang T, Adjei T, et al. Resolving ambiguities in the LF/ HF ratio: LF-HF scatter plots for the categorization of mental and physical stress from HRV. Front Physiol. 2017;8:360.
16. Quer G, Gouda P, Galarnyk M, et al. Inter- and intraindividual variability in daily resting heart rate and its associations with age, sex, sleep, BMI, and time of year: retrospective, longitudinal cohort study of 92,457 adults. PLoS One. 2020;15:e0227709. 17. Morse KW, Subramanian T, Zhao E, et al. Robotic-assisted navigation in single-level transforaminal lumbar interbody fusion reduces surgeons’ mental workload compared with fluoroscopic and computed tomographic techniques: A nonrandomized prospective controlled trial. HSS J. 2025;21:27–34. 18. Van Isseldyk F, Chavalparit P, Bassani J, et al. Low-cost augmented reality system in endoscopic spine surgery: Analysis of surgeon ergonomics, perceived workload and A step-by-step guide for implementation. Global Spine J. 2026;16:873–883. 19. Haffar A, Krueger CA, Goh GS, et al. Total knee arthroplasty with robotic surgical assistance results in less physician stress and strain than conventional methods. J Arthroplasty. 2022;37:S193–S200. 20. Cozzarelli NF, Ashkenazi I, Khan IA, et al. Surgeons experience greater physiologic stress and strain in the direct anterior approach than the posterior approach for total hip arthroplasty. J Arthroplasty. 2024;39:S322–S326.
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From the ¹Department of Orthopaedic Surgery at Rush University Medical Center in Chicago, Illinois, and 2MedStar Health Orthopedics at MedStar Georgetown University Hospital in Washington, DC.
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Beyond the Operating Room: The Growing Role of Business Education in Spine Surgery The spine surgeon model has traditionally been straightforward: build referrals, operate in hospitals, and practice within a largely fee-for-service system while administrators managed margin, throughput, and payer mix. However, that model has changed. Business considerations now affect decisions about employment, ASC participation, technology adoption, and partnerships with hospitals, health systems, and investors. Consolidation has also accelerated, with a recent analysis finding that more than 50% of active physicians worked for hospital systems in 2024, compared with approximately 20% in 2010.1 The question is therefore not whether business literacy matters but whether formal training, most commonly an master’s of business administration, or MBA, meaningfully helps spine surgeons navigate this changing land-
scape. While valuable for some, especially those pursuing leadership or entrepreneurial roles, its value remains heterogeneous, and direct evidence in spine surgery is limited.
Puranjay Gupta1
Why Business Education Has Aditya Mazmudar2 Become More Relevant Evolution of the Spine Surgery Marketplace The strongest argument for business education in spine surgery is environmental change (Table). Previously, independent practices Daniel Park1 were more common, physician ownership was more durable, feefor-service logic was more straightforward, and the surgeon-hospital relationship was
Table. Evolution of spine practice over time and the importance of business education
Dimension Earlier practice environment
Current practice environment
Why it matters for spine surgeons
Practice structure
More independent private practice
More hospital, corporate, and platform employment
Reduces the number of “purely clinical” decisions that are insulated from system strategy
Site of service
Hospital-dominant procedural workflows
Greater ASC migration and scrutiny of outpatient economics
Makes surgeons stakeholders in facility cost, efficiency, and case selection
Technology
Incremental capital requests
High-cost platforms in navigation, imaging, and robotics
Requires sharper thinking about utilization, EBITDA impact, and return on capital
Payment pressure
Volume-based orientation
Cost oversight, prior authorization, and organizational control of margin
Pushes surgeons closer to questions of throughput, documentation, and service-line economics
Abbreviations: ASC, ambulatory surgical center; EBITDA,
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often simpler and more localized. The current environment is materially different. Hospital and corporate consolidation has accelerated, with the share of hospital systems acquiring physician practices increasing from 13.6% in 2012 to 31.2% in 2018, representing a shift with important consequences for pricing, referral control, and bargaining power.1
Spine Surgery as a High-Stakes Economic Specialty Spine surgery is also a particularly highstakes economic specialty. A spine case itself may involve expensive implants, specialized imaging, neuromonitoring, high-cost equipment, longer operating room time, and multidisciplinary perioperative staffing. Furthermore, as enabling technologies such as navigation and robotics platforms become more mainstream, they add to purchasing costs, service contracts, and downstream usecase expectations. Medtronic’s Stealth AXiS platform recently received FDA clearance for spine surgery as part of a system combining imaging, navigation, and robotics.2 That kind of platform expansion is clinically important, but it is equally a capital-allocation problem. A surgeon who does not understand the business case behind such technology is increasingly at risk of being the subject of the decision rather than a participant in it. Why More Surgeons Are Pursuing MBAs It is difficult to disentangle whether growth in physician business education is primarily demand-driven or supply-driven. On the supply side, combined and clinician-facing management pathways are visibly more
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available than they once were. For example, Northwestern University’s Feinberg School of Medicine advertises multiple dual-degree options and specifically offers MD/MBA pathways with its Kellogg School of Management. On the demand side, the language used by these programs is revealing and often frames physician business training around administration, entrepreneurship, and finance, which is aligned with the current anxieties and ambitions of many young surgeons. That demand likely reflects several overlapping forces. One is a leadership aspiration. Physicians increasingly want a seat at the table when hospitals make decisions about budgets, service lines, digital tools, quality targets, and strategic growth. Another is entrepreneurship. Surgeons interested in devices, digital health, biologics, ambulatory platforms, practice operations, or venture-backed innovation now operate in an ecosystem that rewards fluency in capital formation and market positioning. A third is self-protection, where, as employment contracts become more layered and private investment in physician practices becomes more active, many trainees recognize that business illiteracy is a significant disadvantage. Broader labor-market data point in the same direction. A recent US Bureau of Labor Statistics summary noted that employment of medical and health services managers is expected to grow by 28% from 2022 to 2032, far faster than average. 3 At the same time, Financial Times reported that global MBA applications rose 13% in 2025.4 Those figures do not prove that surgeons are using MBA programs, but they do support the larger idea that formal management training remains attractive in a
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health sector that is simultaneously growing, consolidating, and becoming more managerial. For surgical trainees, an MBA may also serve as a differentiator in competitive fields such as orthopedic surgery and neurosurgery, though its value should come from applied skills rather than credentialing alone.
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The same logic applies to multidisciplinary leadership. Modern spine care requires coordination across a variety of healthcare professionals. Surgeons often lead these teams, and business education can offer vocabulary and frameworks for improved team design. In an era when physician burnout remains above 48.9% and clerical work is a major driver of dissatisfaction, leaders who understand workflow and process engineering may have an advantage not only in margin protection but also in preserving their own practice.5
What an MBA Actually Teaches Business education teaches surgeons how organizations work. In spine practice, the translation is immediate. A surgeon evaluating a robotics proposal should be able to ask whether the platform reduces revision risk, The Potential Benefits and the Case cuts fluoroscopy exposure, expands outpatient Against eligibility, improves block utilization, or mereThe Case For ly shifts marketing. A surgeon considering Among the various arguments for an MBA ambulatory surgical center (ASC) ownership (Figure), the strongest is leverage. Physicians should understand distributions, buy-in strucwith clinical authority and business fluency ture, payer mix, facility utilization, and exit Figure. Benefits and competencies from an MBA for spine surgeries risk. A surgeon building a “program of excellence” should know how referral leakage occurs, how advanced practice provider staffing changes clinic access, how operating room turnover affects contribution margin, and how hospital and payer incentives may diverge from surgeon incentives. These are business questions, but they are also care-delivery questions.
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may be better positioned to lead departments and resist poorly aligned administrative decisions. In spine surgery, where technology adoption and site-of-service strategy can alter both quality and economics, that dual fluency may improve decision-making at the organizational level. Business training may also improve contract negotiation, especially for employed surgeons navigating compensation formulas, call pay, academic support, noncompete language, equity participation, or ASC governance documents. A second major benefit is career flexibility. Burnout and payer pressure are pushing more physicians to consider hybrid careers or earlier transitions away from full-time clinical practice. In that setting, an MBA can broaden the aperture and support a move into administration and entrepreneurship. Kellogg’s own program materials present that logic and emphasize innovation and consulting as downstream applications of physician business training. There may also a be financial upside, but the evidence is limited. In the general MBA market, median starting salaries can be strong. A recent Wall Street Journal guide cited a median MBA starting salary of $120,000, while also noting that MBA education often costs more than $60,000 and that many graduates carry substantial debt.6 For surgeons, however, the relevant return is more often indirect and mediated through leadership compensation or better negotiation of existing roles.
The Case Against The case against the MBA should also be considered. First, business training is expensive,
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with recent reports suggesting MBA tuition is often well into the tens of thousands, frequently much higher at private programs, and many medical graduates already carry heavy debt burdens. The median indebtedness of U.S. medical students with loans was reported at $205,000 in 2023, and adding another degree can further exacerbate debt.7 Second, there is an opportunity cost, as time spent in classrooms is time not spent operating, building referral networks, or being present for family. Feinberg’s dual-degree pathway, for example, is structured over 5 years, with a substantial block of time devoted to business school training. Third, a motivated surgeon can learn healthcare finance and even basic valuation through executive courses and disciplined self-study. Leadership itself is also not reducible to credentialing. Some outstanding physician leaders have no MBA, and some MBAs never become effective leaders. If the degree becomes a checkbox rather than an educational experience, its marginal value will decline.
Is an MBA Worth It for Every Spine Surgeon? The value of an MBA depends heavily on career goals. For academic surgeons, it may support administrative leadership or research commercialization; for private practice surgeons, it may aid practice management, growth planning, ancillary integration, and negotiation. For employed surgeons, it may provide leverage in contract negotiations and hospital leadership pathways. Entrepreneurs may derive the greatest benefit in startups, device development, digital
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health, or venture-facing roles. By contrast, surgeons focused primarily on clinical practice may find limited incremental value in a formal MBA compared with shorter, targeted business education. Importantly, an MBA is not the only pathway to business literacy. Many relevant competencies can be developed through executive education, hospital leadership tracks, society-based courses, mentorship from practice leaders, and direct experience with service-line administration, ASC governance, or industry collaboration. For many spine surgeons, these focused alternatives may offer more practical exposure to finance, operations, negotiation, and health care economics with less cost and time away from practice.
Future Directions The relevance of business education in spine surgery is likely to increase. Artificial intelligence is beginning to reshape documentation and workflow, with a narrative
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review finding that ambient documentation technology reduced physician burnout by up to one-third in participating systems, suggesting that operational and digital decisions will increasingly have direct workforce consequences. 8 Robotics and navigation platforms continue to expand, requiring more disciplined capital decisions. ASC migration remains a live strategic frontier where competing consolidation and anti-trust litigation continue to influence the shape of the practice. For that reason, the argument for business education should be framed as a response to a genuine change in the structure of practice. Business literacy is becoming a practical competency for surgeons who wish to influence the long-term direction of spine care. An MBA is one powerful way to acquire that competency, but not the only way. Regardless of whether a surgeon chooses to pursue an MBA, the importance of business literacy in modern spine practice is increasingly difficult to ignore. l
References 1. Young GJ, Duran D, Ratto I, Senier L, Post B. Hospital system acquisition of physician practices. JAMA Netw Open. 2026;9(6):e2618414. 2. Medtronic receives FDA clearance for Stealth AXiS TM surgical system, first integrated planning, navigation and robotics platform for spine surgery [press release]. Medtronic. February 13, 2026. Accessed June 11, 2026. https:// news.medtronic.com/2026-02-13Medtronic-receives-FDA-clearance-forStealth-AXiS-TM-surgical-system,-firstintegrated-planning,-navigation-androbotics-platform-for-spine-surgery
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3. Burden M, Astik G, Auerbach A, et al. Identifying and Measuring Administrative Harms Experienced by Hospitalists and Administrative Leaders. JAMA Intern Med. 2024;184(9):1014-1023.
6. Thomas P. Starting salaries are soaring. Wall Street Journal. November 15, 2021. Accessed June 11, 2026. https://www. wsj.com/lifestyle/careers/m-b-a-starting-salaries-are-soaring-11636952464
4. Jack A. Wharton tops 2025 FT MBA ranking despite strong European competition. Financial Times. February 16, 2025. Accessed June 11, 2026. https://www. ft.com/content/90728804-2f4d-4ad4826e-71c58561fc71?syn-25a6b1a6=1
7. Ramesh T, Kadakia KT, Liu M, Yu H. Federal loans among US medical students. JAMA. 2026;335(2):179-181.
5. Guille C, Sen S. Burnout, depression, and diminished well-being among physicians. N Engl J Med. 2024;391(16):1519-1527.
8. Razaghi M, Hafez A, Farina JM, et al. Transforming clinical documentation with ambient artificial intelligence (AI) scribes: a narrative review of technology, impact, and implementation. Cardiovasc Diagn Ther. 2026;16(1):11.
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