Heterotopic Ossification Following Direct Anterior Total Hip Arthroplasty With and Without Post-Operative Non-Steroidal Anti-inflammatories Brandon Naylor
1 DO,
Matthew Caid
1 DO,
Cesar Iturriaga
2 DO,
Yash B. Bisen
Background
Methods
Total Hip Arthroplasty (THA) using the Direct Anterior (DA) approach has been extremely successful, with high rates of patient satisfaction and functional recovery. [1] However, up to half of patients who undergo THA experience heterotopic ossification post operatively. While HO is often asymptomatic, it can decrease range of motion and cause pain. [2] Multimodal pain strategies using NSAIDs have recently been employed perioperatively. NSAIDs reversibly inhibit cyclooxygenase; this decreases the production of prostaglandins and thromboxanes. By mitigating the inflammatory effects of these eicosanoids, NSAIDs have not only proven to be a successful alternative to the complication ridden opioid pain medications, but have also been shown to expedite the recovery process. Celecoxib, specifically, is commonly administered as a form of perioperative pain management, and it has demonstrated success in HO prophylaxis. [3] No study has evaluated the incidence of HO in DA THA using celecoxib. The goal of our study was to perform a retrospective chart review to compare the incidence of HO in those undergoing DA THA with and without the addition of extended perioperative celecoxib administration.
A retrospective chart review was performed. Patients were grouped according to those without (control group) and with (treatment group) a prescription for Celebrex at discharge. Pelvis and hip radiographs were independently reviewed by two separate orthopedic fellows blinded to Celebrex administration. X-rays were categorized according to the Brooker and modified Brooker classification system for HO. Preoperative and 2 week, 6-week, 3-month, and 1-year postoperative x-rays were evaluated. Patients without a minimum 3-month follow-up x-ray were excluded from analysis. Multivariate logistic regression analysis was performed to calculate oddsratios (OR) and 95% confidence intervals (95%CI) on the effects of celecoxib on the incidence of HO. A two-tailed p-value less than 0.05 was considered statistically significant. To reduce the probability of a type I error, Bonferroni method was used to adjust for multiple comparisons at an alpha level of 0.05. All statistical analyses were performed with SPSS version 26 (IBM Corporation, Armonk, New York).
An Example of Grade 4 Heterotopic Ossification developing after Direct Anterior Total Hip Arthroplasty: Pre-op Post-op 03/03/20 Post-op 11/15/16
Results Table 1. Incidence of Heterotopic Ossification between Celecoxib Groups
AnteriorPosterior
3 BA,
Keith Reinhardt
4 MD
Table 3. Incidence of Heterotopic Ossification with or without use of Celecoxib and Aspirin
* Chi squared test of Independence.
Conclusions A total of 766 DA THAs were performed during the study period. 76 patients were excluded due to absent or insufficient radiographic follow-up, leaving 688 cases included in the final analysis. The total incidence of HO in the study population was 9.6% (66/688). 14.3% (52/364) of patients in the control group, those who did not receive Celebrex, went on to develop HO following THA (OR 4.53, p<0.001), while only 4.3% (14/324) developed HO in the treatment group (OR 0.22, p<0.001). In total, 9 patients (1.3%) went on to develop clinically significant HO (Booker 3 or greater); and 8 of them (2.2%) were in the control group while 1 (0.3%) of them was in the treatment group (p<0.001). The incidence and severity of HO in patients who received both celecoxib and ASA postoperatively was reduced. Multivariate logistic regression model was utilized to determine the influence of postoperative celecoxib. The model demonstrated that patients who did not receive postoperative celecoxib were 4.53 times as likely to develop HO than those who did (95% CI: 2.34 – 8.78; p<0.001). Our results demonstrate a significantly reduced incidence of HO formation following DA THA when using extended analgesic celecoxib as part of a multimodal pain protocol. More importantly, in our cohort, those given celecoxib postoperatively only demonstrated one case of severe HO versus eight cases in those without celecoxib. Additionally, those on low dose ASA for VTE prophylaxis demonstrated a further reduced incidence of HO development, although not statistically significant.
Future Directions
* Based on two sided z tests for column proportions, adjusted with Bonferroni correction for multiple comparisons.
Lateral
Table 2. Incidence and Odds of Heterotopic Ossification of Significant Predictors in Regression Model
Hypothesis There is a statistically and clinically significant reduction in formation of Heterotopic Ossification following Direct Anterior Total Hip Arthroplasty when Celecoxib is given postoperatively.
Figure 7: Independent CRISPR knockout of CDK4 or CDK6 does not cause dropout in most breast cancer cell lines studied.
* Odds based on Multivariate Regression including above significant actors, adjusting for age, sex, BMI, history of hip trauma, history of prior hip surgery, and postoperative ASA use. Logistic regression model was significant (p=<0.001) with appropriate goodness of fit.
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Prospective Randomized Studies Identification of the ideal dosage, duration, and formulation to both reduce the risk of HO and optimize the multimodal pain management strategy. Exploring the efficacy of other NSAIDs and COX inhibitors.
Resources [1] (Arthroplasty Using a Direct Anterior or Posterolateral Approach: A Randomized Controlled Trial. J Arthroplasty 2017. [2] Alijanipour P, Patel RP, Naik TU, Parvizi J. Heterotopic Ossification in Primary Total Hip Arthroplasty Using the Direct Anterior vs Direct Lateral Approach. J Arthroplasty 2017. [3] Lavernia CJ, Contreras JS, Villa JM, Rossi MD. Celecoxib and heterotopic bone formation after total hip arthroplasty. J Arthroplasty 2014.