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The International Society For Fracture Repair Newsletter January 2013

From the President, Dear ISFR colleagues, It is a great honor for me to address you as the president of the International Society for Fracture Repair. I am proud of the traditions of the ISFR, and I intend to maintain those precious traditions. Fracture healing has been a major medical issue since primeval times, and nonunions have been ever-present. In recent years, the population of the elderly has been increasing dramatically all over the world, and along with this increase, fragility fractures have been rising as a big problem. During our last biennial conference, held on 6-9 November 2012 in Kyoto, Japan, we chose these two, i.e. nonunions and fragility fractures, as our topics and had fruitful discussions about them. Over the next two years, during my presidency, the treatment of fragility fractures and the prevention of secondary fractures will be the main themes of the ISFR in addition to the stimulation of fracture healing and the prevention of nonunions, which are the eternal themes of the International Society for Fracture Repair. I will do my utmost to encourage research work in these fields in collaboration with the Fragility Fracture Network, International Osteoporosis Foundation, Osteoporotic Fracture Campaign, Bone and Joint Decade and other groups. The exchange of knowledge and collaborative interaction between groups or individuals are of great importance in research work these days, and the ISFR is prepared to nurture young investigators. We provide two fellowships, the ISFR Travel Fellowship and the ISFR Research Fellowship, for young researchers to foster intellectual exchange, so please check our website for announcements of these opportunities. I look forward to your active participation in ISFR events and hope you will make effective use of your ISFR membership for yourselves, as well.

Takashi Matsushita President of ISFR

ISFR 13th Biennial Conference Award Winners The awards committee selected three award winners, Dr. Noriko Harada of Teikyo University School of Medicine for Best Scientific Paper Award, Dr. Yohei Kawakami of Kobe University Graduate School of Medicine for Young Investigator Award, and Dr. Kenji Tobita of Labour Health Welfare Organization/Kanto Rosai Hospital for Best Poster Award. The abstracts for awards are as follows:

Noriko Harada, Deprt. of Orthop. Surg.,Teikyo Univ.Sch.of Med, Winner of the Best Scientific Award at ISFR 13th Biennial Conference, Kyoto, Japan

Reconstruction of bone defects by mesenchymal stem cell derived chondrogenic cells (MSC-DC) Noriko Harada1, Yoshinobu Watanabe1, Satoshi Abe1, Kenji Sato1, Katsuyuki Yamanaka2, Yuhiro Sakai2, Tadashi Kaneko2, Takashi Matsushita1 1 Dept. of Orthop. Surg.,Teikyo Univ.Sch.of Med, 2 GC CORP. Purpose: The purpose of this study was to evaluate the effects of implantation of mesenchymal stem cell derived condrogenic cells (MSC-DC) on bone healing in segmental defects in rat femur. Methods: Five-millimeter segmental bone defects were produced in the mid-shaft of the femur of Fisher 344 rats and stabilized with external fixator. The Treatment Group received MSC-DC, seeded on a PLGA scaffold, locally at the site of the bone defect, and Control Group received scaffold only. The healing processes were monitored radiographically (Softex), and studied radiographically (Micro-CT) and histologically.

Results: All the bone defects in the Treatment Group healed radiographically with bridging callus formation at 4 weeks after the procedure, while none of the Control Group had achieved bone union. Micro-CT showed that newly formed bone volume in the Treatment Group at 16 weeks was 1.5 times that of unaffected side. Histological examination showed that the implanted scaffold of the Treatment Group were covered with periosteum-derived bridging callus and filled with cancellous bone-like tissue derived from endochondral ossification. Conclusion: The results of this study suggest that implantation of MSC-DC surprisingly enhances bone healing in segmental bone defects in rat much better than previously reported similar therapy using MSC.

ISFR 13th Biennial Conference Award Winners

Dr. Yohei Kawakami of Kobe University Graduate School of Medicine for Young Investigator Award

The new strategy for fracture healing by ex-vivo expanded bone marrow CD34 positive progenitor cells Yohei Kawakami1,2, Msaaki Ii1,3, Atsuhiko Kawamoto1, Tomoyuki Matsumoto2, Yutaka Mifune2, Taro Shoji1, Tomoaki Fukui1, Ryosuke Kuroda2, Msahiro Kurosaka2, Takayuki Asahara1 1 Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, 2 Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 3 Department of Pharmacology, Osaka Medical College

model of femoral fracture was created in nude rats with periosteum cauterization, which leads to nonunion at 8 weeks post-fracture. Rats received local administration of the following cells or PBS alone (1)cEx-BM, (2)BM, (3) GM-PB CD34+ cells or (4)PBS.

Results: Our 7-day culture expansion technique allowed us to obtain 23 times of BM CD34+ cells maintaining 60% purity of CD34 positivity. cEx-BM CD34+ cells exhibited striking therapeutic efficacy for unhealing fracture promoting neovascularization and osteogenesis in sites of fracture. Moreover, cEx-BM CD34+ cells showed high caIntroduction: Failures in fracture healing are mainly pacity of colony formation and osteogenic differentiation. caused by a lack of neovascularization. We have previously demonstrated that G-CSF-mobilized peripheral Conclusion: BM CD34+ cells can be obtained from the blood (GM-PB) CD34+ cells, an endothelial progenitor fracture site at the time of primary operation and stored enriched cell population, contributed to fracture healing for further use, autologous culture expanded BM CD34+ via vasculogenesis and osteogenesis. We postulated the cell transplantation therapy would be not only a simple hypothesis that local transplantation of culture expanded but also powerful therapeutic strategy for unhealing fracbone marrow (cEx-BM) CD34+ cells could exhibit thera- ture. peutic potential for fracture healing.

Materials: BM CD34+ cells were cultured in specific medium with 5 growth factors for 1week. A reproducible 3

ISFR 13th Biennial Conference Award Winners

Measurement of mechanical properties on gap healing in a rabbit osteotomy model until the remodeling stage Kenji Tobita1, Hiroshi Okazaki1, Wakyo Sato3, Takuya Matsumoto3, Masahiko Bessho2, Satoru Ohashi4, Isao Ohnishi2 1 Japan Labour Health and Welfare Organization, Kanto Rosai Hospital, 2 International University of Health and Welfare, 3 Tokyo Metropolitan Tama Medical Center, 4 Dept. of Orthop. Surg., Faculty of Medicine, University of Tokyo The most important issue in the assessment of fracture healing is to acquire information about the restoration of themechanical integrity of bone. Many researchers have attempted to monitor stiffness either directly or indirectly for the purpose of assessing strength, as strength has been impossible to assess directly in clinical practice. The purpose of this study was thus to determine the relationship between bending stiffness and strength using mechanical testing at different times during the healing process. Unilateral, transverse, midtibial osteotomies with a 2-mm gap were performed in 28 rabbits. The osteotomy site was stabilized using a double-bar external fixator. The animals were divided into four groups (n=7/group/time point; 4, 6, 8 and 12 weeks). A series of images from micro-computed tomography of the gap was evaluated to detect the stage of fracture healing and a 4-point bending test was performed to measure stiffness and strength.

Dr. Kenji Tobita of Labour Health Welfare Organization/Kanto Rosai Hospital for Best Poster Award.

Formation of cortex and medullary canal at the gap was seen in the 12-week group and would represent the remodeling stage. In addition, the relationship between stiffness and strength remained almost linear until at least 12 weeks. However, stiffness recovered much more rapidly than strength. Strength was not fully restored until the later stages of fracture healing. However, the current study demonstrated that stiffness could be monitored as a surrogate marker of strength until at least the remodeling stage.

Recommendation for measuring clinical outcome in distal radius fractures – A core set of domains for standardized reporting in clinical practice and research On behalf of the IOF-ISFR distal radius working group

Fractures of the distal radius are the second most commonly presenting fracture in the elderly and hence optimal and efficient management has potential for substantial impact. 1 More than 450,000 occur annually in the United States.2 The common immediate symptoms of pain and temporary loss of upper extremity function cause short-term impact on quality of life and role functioning.3,4 A proportion of cases also experience long-term loss of upper extremity function and impaired role functioning.3, 5, 6 Subsets of distal radius fractures (DRF) are potential sentinel fractures for underlying issues of bone strength .7 The risk of recurrent fractures in the 10 years following a distal radius fracture is significantly higher than for those who have yet to experience a fracture; and is substantially elevated for those who have other osteoporotic fractures.8 High-energy fractures and fragility fractures require different levels of intervention for diagnosis and treatment. Whereas routine fracture treatment may suffice for many, fragility fractures may present the first opportunity to diagnose osteoporosis and potentially initiate treatment. Current evidence suggest certain populations who may respond to drug therapy for osteoporosis are undertreated.9 We propose that early detection and treatment may prevent adverse outcomes in either pain disability or overall bone health and require standardized assessment approaches with valid instruments. As common as this fracture is, current DRF literature highlights the lack of sufficient high-quality research to define intervention or evaluation of outcome.10, 11 In particular, a lack of consistent measurement of outcomes has been cited as a limitation in current research.11, 12 A solution to inconsistent or inadequate outcome evaluation in clinical studies and practice is the establishment of core consistent measurement that individuals would apply uniformly, and augmented as needed. Core sets define the essential set of measures or domains to be included in clinical research or practice in a given field.13, 14 The International Classification of Functioning, Disability and Health (ICF) core sets are based on a process of delineating the categories from within this classification system that apply to a given condition (such as wrist fracture) and form what is reported to be a comprehensive foundation of content for outcomes in that area.15, 16 The process for establishing these core sets depends on review of quantitative and qualitative evidence on disability for a specific patient population, consultation with experts and a consensus conference. For example, core sets in arthritis are derived by patient and provider consensus and measures are chosen based on evidence of their measurement properties.17 The Distal Radius Working Group of the International Society for Fracture Repair (ISFR) and the International Osteoporosis Foundation (IOF) identified a need for consistent measurement in DRF and established a process to move forward on

identifying key measures that would be relevant for clinical practice and clinical research The purpose of the working group was to review the literature on outcome measures used in distal radius fracture trials, cohort studies and case series and interpret those in light of future potential to contribute to a core set of domains. More on this will be presented at this year’s AAOS in Chicago. Friday March 22, 2013, at 8:30 AM in Room S102, McCormick Place. References: 1. Shauver MJ, Yin H, Banerjee M et al (2011) Current and future national costs to medicare for the treatment of distal radius fracture in the elderly. J of Hand Surg 36: 1282-1287. 2. Koval K J, Zuckerman JD (2006) Handbook of fractures. 3rd Edition Lippincott Williams & Wilkins. Philadelphia, USA. 3. MacDermid JC, Roth JH, Richards RS (2003) Pain and disability reported in the year following a distal radius fracture: a cohort study. BMC Musculoskelet Disord 31;4:24. 4. MacDermid JC, Richards RS, Roth JH (2001) Distal radius fracture: a prospective outcome study of 275 patients. J Hand Ther ;14:154-69. 5. MacDermid JC, Roth JH, McMurtry R (2007) Predictors of time lost from work following a distal radius fracture. J Occup Rehabil17:47-62. 6. Harris JE, MacDermid JC, Roth J (2005) The International Classification of Functioning as an explanatory model of health after distal radius fracture: a cohort study. Health Qual Life Outcomes;3:73. 7. Hollevoet N, Verdonk R, Kaufman J et al (2011). Osteoporotic fracture treatment. Acta Orthop Belg; 77: 441-447. 8. Hodsman AB, Leslie WD, Tsang JF, Gamble GD (2008) 10-year probability of recurrent fractures following wrist and other osteoporotic fractures in a large clinical cohort: an analysis from the Manitoba Bone Density Program. Arch Intern Med Nov 10;168:2261-7. 9. Iba K, Takada J, Hatakeyama N, et al (2006) Underutilization of antiosteoporotic drugs by orthopedic surgeons for prevention of a secondary osteoporotic fracture. J Orthop Sci ;11:446-9. 10. Abraham A, Handoll HH, Khan T (2008) Interventions for treating wrist fractures in children. Cochrane Database Syst Rev;(2):CD004576. 11. Handoll HH, Madhok R, Howe TE (2006) Rehabilitation for distal radial fractures in adults. Cochrane Database Syst Rev;3:CD003324. 12. Hoang-Kim A, Scott J, Micera G et al (2009) Functional assessment in patients with osteoporotic wrist fractures treated with external fixation: A review of randomized trials. Arch Orthop Trauma Surg 129: 105-11. 13. Stucki G, Grimby G (2004) Foreword: applying the ICF in medicine J Rehabil Med 36: 5-6. 14. Cieza A, Ewert T, üstün TB, et al (2004) Development of ICF Core Sets for patients with chronic conditions. J Rehabil Med; 36 (suppl 44): 9-11. 15. World Health Organization (2001) International classification of functioning, disability and health (ICF). Geneva, Switzerland, 10-20. 16. ICF Core Set Projects (2010) ICF Research Branch website. Accessed April 12, 2012. 17. Bellamy N, Kirwan J, Boers M et al (1997) Recommendations for a core set of outcome measures for future phase II clinical trials in knee, hip and hand osteoarthritis. Consensus development at OMERACT III. J Rhematol 24: 799-802.

Capture the fracture IOF’s new global campaign to facilitate the implementation of Fracture Liaison Services (FLS) for secondary fracture prevention

Worldwide, standards of care to prevent secondary fractures are appallingly low. Eighty per cent of fragility fracture patients are neither assessed nor treated for osteoporosis or falls risk – even though they are twice as likely to suffer additional fractures as compared to people who have not suffered a fracture.

Where we are now

Internationally endorsed standards Striving to set a global standard of care for fracture patients, Capture the Fracture developed a Best Practice Framework (BPF): 13 criteria for best practice that define the essential and aspirational building “By missing the opportunity to respond to the first fracture, blocks necessary to implement a successful FLS. healthcare systems around the world are failing to prevent the second and subsequent fractures.” The centrepiece of the campaign, the BPF: Professor Kristina Åkesson, Sweden · Serves both as a benchmark for existing and a model for developing FLS systems around the world. Directly addressing the secondary fracture care gap, the International · Is the measurement tool for IOF to award “Capture the Fracture Osteoporosis Foundation (IOF) introduces Capture the Fracture: a Best Practice Recognition” in celebration of successful FLS worldglobal campaign to facilitate the implementation of Fracture Liaison wide. Services (FLS) for secondary fracture prevention. We believe this is

the single most important thing that can be done to directly improve The BPF is designed to be both achievable and ambitious. Each critepatient care and reduce spiraling fracture related healthcare costs rion is divided into 3 levels of achievement and each is weighted worldwide. based on how essential they are to a successful FLS – the combination of which will lead to an overall FLS composite performance at a Gold, Communicated through a dedicated website, Silver or Bronze level. By doing this, the steering committee enables, Capture the Fracture serves as a hub recognition of systems who have achieved the most essential elefor health care providers to come together to share their FLS proments, while leaving room for improvement towards implementing grammes and local implementation strategies and promotes FLS by the aspirational elements. offering best practice, recognition and resources. Capture the Fracture was born from an IOF Position Paper supporting the implementation of FLS, published in the May 2011 issue of Osteoporosis International ( pubmed/21607807) and was later the subject of World Osteoporosis Day 2012 ( A steering committee, led by Professor Kristina Akesson, brought the campaign to life with an official launch at the IOF European Congress on Osteoporosis and Osteoarthritis in Bordeaux, France in March 2012. Overall, the campaign is structured to cover three overarching goals: Provide internationally endorsed standards for best practice · Best Practice Framework ( for FLS) · Best Practice Recognition Showcase of best practices Facilitate change at a national level Implementation guides and toolkits Mentoring programmes Grant programme for developing systems

· · · ·

Raise awareness of FLS for preventing secondary fractures An on-going communications plan Anthology of literature, worldwide surveys and audits International coalition of partners and endorsers

· · ·

When developing the BPF, the steering committee sought input and endorsement from industry leaders in many countries to form a global document. Being mindful of the varying healthcare systems around the world, the BPF is designed to facilitate the implementation of FLS using the existing procedures that are currently in place as they correspond to each underlying health care system. “The Best Practice Framework will provide a basis for secondary prevention throughout Europe and worldwide” Professor Cyrus Cooper, United Kingdom Application and Recognition Putting the BPF into action, healthcare systems are encouraged to submit their FLS through the web-based questionnaire, at, which gathers information about the FLS and its achievements as they correspond to the Best Practice Framework. Applicants achieving Capture the Fracture Best Practice Recognition of Bronze, Silver or Gold will be recognised by IOF in the following ways: · Placement of the applicant’s FLS on the Capture the Fracture website’s interactive map, including the system name, location, link and program showcase. · Awarded use of the IOF approved, Capture the Fracture Best Practice recognition logo for use on the applicant’s websites and materials.

Get involved Capture the Fracture invites you to join our efforts in facilitating the implementation of Fracture Liaison Services for secondary fracture prevention.

Research Library The Capture the Fracture website – offers a Research Library containing over 500 global publications on secondary fracture prevention. The library includes publications on country audits & surveys, fracture epidemiology, case findings and health economics analysis. Partners An international coalition of partners, nearing 200 participants, has been developed. Consisting of multidisciplinary healthcare providers, members of national societies and industry organizations, the coalition is instrumental in supporting and promoting Capture the Fracture within their local communities. Looking ahead-2013 and beyond As Capture the Fracture moves into phase II of development the campaign will focus on facilitating change and raising awareness to support the implementation of FLS globally. Capture the Fracture will showcase implementation guides and national toolkits as they are developed by countries. A mentor programme will be formed between sites that have achieved Best Practice Recognition and those systems that are in early stage development. A grant programme will be established to aid clinical systems around the world which require financial assistance to establish FLS. Each of these activities is an opportunity to create a global network to support the sharing of successes and challenges that will be faced in the process of implementing best practice. Making it official Celebrating a successful first year, Capture the Fracture will be recognized at the ESCEO/IOF Rome meeting in April, 2013 by: · Publishing a Position Paper on Capture the Fracture and Best Practice Framework · Launching ‘officially’ the Capture the Fracture website · Accepting FLS applications for Capture the Fracture Best Practice Recognition

Email to: · Join the Coalition of government agencies, companies, professionals, and healthcare organizations who support secondary fracture prevention · Submit your FLS for Capture the Fracture Best Practice Recognition · Sign up for the Newsletter to receive the Capture the Fracture newsletter

International Society For Fracture Repair’s Young Investigator Network

The ISFR is dedicated to achieving scientific excellence in the field of fracture repair. This would not be achievable without the initiative and dedication of Young Investigators. The ISFR would like to establish the YIN to exchange ideas among peers and mentors.

At this year’s biennial conference held in Kyoto, Japan Amy Hoang-Kim launched the first meeting of the Young Investigator Network. The idea behind this network is to create a link between science and innovators. Interactive sessions with mentors, exchanges abroad, initiation of workshops were some of the ideas brought forward by some of the attendees on November 8th, 2012. The challenge in the future will be to broaden intellectual boundaries by increasing exposure and communication to labs and operating rooms abroad. We will meet informally before the next biennial conference of the ISFR and one of the goals of these meetings will be to form a sub-committee of Young Investigators to liaise with the board members. Here is an introduction to one of the Network’s newest member from the United Kingdom who was also a presenter at this year’s biennial conference in Japan.: Dr. Mehran Moazen.

Mehran Moazen: graduated in Mechanical Engineering from University of Mazandaran (Iran) in 2005 and completed his PhD in Medical Engineering at the University of Hull (UK) in 2008. He then worked as a consultant engineer at the University of Hull for Smith & Nephew for about a year. In June 2009, he moved to University of Leeds as a Post-doctoral Research Fellow investigating the biomechanics of periprosthetic femoral fracture fixation as a part of a research program funded by British Orthopaedic Association (BOA) through the Latta Fellowship that has been led by Prof Eleftherios Tsiridis. In June 2012, he received a prestigious five years research fellowship from Royal Academy of Engineering to investigate the biomechanics of craniosynostosis at the University of Hull, he will commence his new post in March 2013.

Engineering (iMBE) at the University of Leeds are one of the world leading groups in the field of joint replacement. Dr Moazen presented his work on periprosthetic femoral fracture fixation in 13th Biennial conference of International Society of Fracture Repair in Kyoto, Japan. Below is an overview of his work and colleagues at iMBE: The overall aim of this research program is to optimize periprosthetic femoral fracture (PFF) fixation. These fractures can occur following total hip arthroplasty (THA) and the management of these fractures are challenging due to the presence of the underlying prosthesis. Over recent years there have been a number of PFF fixation failures that is of immense concern due to increasing number of THAs. Over past three years we have been developing a series of experimental and computational models of PFF fixation. The computational models allow many more parameters to be tested than would be possible experimentally. Further these models allow us to analysis the internal stress distribution, risk of failures and capacity for fracture healing. However, computational models are sensitive to the input parameters and should be corroborated against experimental models and validated against in vivo models. Therefore, the team has been involved in several sensitivity, corroboration and validation studies. Meanwhile the clinical team have been continuously enriching this program with series of clinical case studies. Our results so far highlight the effect of (1) fracture stability both in terms of fracture angle and fracture gap and (2) post operative load bearing on PFF fixations. We have found that the aforementioned parameters considerably alter the risk of fixation failure and level of interfragmentary motion. Also, our computational study based on a clinical case showed that rigid fixation as a result of short bridging length, suppressed the interfragmentary motion and in fact led to nun-union and ultimately fixation failure. In this case fracture was healed under a more flexible fixation where the computational model also predicted interfragmentary motion in the range of 0.2-1mm that is shown to promote callus formation. In summary our results highlights the role of fracture configuration in PFF fixations and shows that rigid fixations that suppress fracture movement could be detrimental to healing. Various parameters have been shown to contribute to current clinical failure of PFF fixation and the team is currently working to optimize PFF fixations.

If you would like to attend the next Network meeting, please The Medical and Biological Engineering (MBE) Research email Amy Hoang-Kim at isfr.fractures@gmail com or ProfesGroup at the University of Hull are internationally recognised sor Allen Goodship at for their computational modelling of bone and craniofacial systems in particular. The Institute of Medical and Biological


The advanced clinical evidence (ACE) report is a critical summary of the important details from a selected publication that assess both quality and the potential for bias. The report contains a synopsis of the publication, funding sources and implications, the principle research question, study groups, methods, outcome measures, important findings and their implications for the medical community. More information can be found at

External Fixation Versus Open Reduction With Plate Fixation for Distal Radius Fractures: A Meta-Analysis of Randomized Controlled Trials Meta-Analysis Conference Report

Quality of Evidence Score for this ACE Reports: Not Applicable(Conference Report)*

Synopsis This meta-analysis included 10 studies that compared the effectiveness of external fixation and open reduction with internal fixation (ORIF) using plates for patients with distal radius fractures. The pooled results demonstrated that patients who received ORIF had significantly lower disability scores than those who received external fixation. ORIF patients also experienced less ulnar variance and infection than external fixation patients. The two treatments did not differ significantly in any other clinical outcome. Results therefore favour ORIF as the optimal treatment for distal radius fractures.

Why Was This Study Needed Now? Recent research has shown evidence for the effectiveness of both external fixation and ORIF for the treatment of distal radius fractures. There is some debate about which method should be used to achieve optimal results. The purpose of this meta-analysis and systematic review was to compare external fixation and ORIF in order to determine the most effective treatment for patients with distal radius fractures.

What Was The Principle Research Question? Do the outcomes of external fixation and ORIF differ in terms of wrist range of motion, radiographic parameters, grip strength, disability scores, complications and rate of re-operation in patients with distal radius fractures?

What Where The Important Findings?  Patients in the ORIF group had significantly lower Disabilities of the Arm, Shoulder and Hand (DASH) scores than those in the external fixation group (pooled mean difference=-5.92, 95% CI: -9.89 to -1.96, p<0.01, I2 = 39%)  There was significantly less ulnar variance in the ORIF group than in the external fixation group (pooled mean difference= 0.70, 95% CI -1.20 to -0.19, p=0.006, I2 = 0%)  The rate of infection was significantly lower in the ORIF group than in the external fixation group (pooled risk ratio=0.37, 95% CI 0.19 to 0.73, P = 0.004, I2 = 0%)  The two groups did not differ significantly in all other clinical outcomes. OTA: Open reduction with plate fixation for the treatment of distal radius fractures. OrthoEvidence Advanced Clinical Evidence Report. In: Ortho Evidence. Created Oct 26, 2012. Last modified Dec 14, 2012. Retrieved Dec 14, 2012 from


The advanced clinical evidence (ACE) report is a critical summary of the important details from a selected publication that assess both quality and the potential for bias. The report contains a synopsis of the publication, funding sources and implications, the principle research question, study groups, methods, outcome measures, important findings and their implications for the medical community. More information can be found at

Denosumab Treatment in Postmenopausal Women with Osteoporosis Does Not Interfere with Fracture-Healing: Results from the FREEDOM Trial J Bone Joint Surg Am. 2012 Oct 24. doi: 10.2106/JBJS.K.00774 Level II – Randomized Trial

What Was The Principle Research Question? Does Denosumab lead to an increased occurrence of delayed fracture healing and adverse events in postmenopausal female patients with osteoporosis?

What Where The Important Findings? Quality of Evidence Score for this ACE Report: 8

386 nonvertebral fractures occurred in 303 of the Denosumab patients (146 fractures in 123 patients occurred within 6 weeks before or after a dose of Denosumab, 25 of the 146 fractures occurred within one week before or after a dose, and 4 of the 25 fractures occurred within one day before or after a dose); 465 nonvertebral fractures occurred in 364 of the placebo patients

23 Denosumab patients and 35 placebo patients had two or more nonvertebral fractures in separate clinical events (<10%)

Delayed healing occurred in 2 patients of the Denosumab group (for fractures that occurred at 7 weeks and 16 weeks after the administration of Denosumab) and 5 patients of the placebo group (for fractures that occurred at 13, 15, 17, 18 and 19 weeks after the administration of placebo)

None of the patients in the Denosumab group and 1 patient in the placebo group had nonunion

Surgery was required for 79 fractures in the Denosumab group (65 patients) and 120 fractures in the placebo group (100 patients)

Out of the patients who had nonvertebral fractures, a greater proportion of the placebo group (5%) had a complication associated with the fracture or its management than the Denosumab group (2%) (p=0.009)

Synopsis 7808 postmenopausal female patients with osteoporosis were randomized to receive 60 mg of Denosumab or placebo every six months for 3 years. Over the course of the study, non-vertebral fractures occurred in 303 patients in the Denosumab group (386 fractures) and 364 in the placebo group (465 fractures). 79 of the fractures in the Denosumab group and 120 fractures in the placebo group were treated with surgery. Delayed healing was seen in 2 Denosumab patients and 5 placebo patients. Lastly, a significantly smaller proportion of patients in the Denosumab group experienced a complication associated with a fracture or its management.

Why Was This Study Needed Now? Osteoporosis patients who sustain fragility fractures need to obtain treatment (for osteoporosis), as fragility fractures tend to increase the risk of subsequent fracture. Anti-resorptive agents such as Denosumab appear to reduce bone resorption, decreasing the risk of new fractures. The purpose of this study was to follow-up the FREEDOM trial, in order to examine adverse events and the possibility of delayed fracture healing related to Denosumab.

FREEDOM RCT follow-up: Denosumab does not delay fracture healing in osteoporosis patients. OrthoEvidence Advanced Clinical Evidence Report. In: Ortho Evidence. Created Nov 09, 2012. Last modified Dec 14, 2012. Retrieved Dec 14, 2012 from *Details about the Quality of Evidence Score for this ACE Report can be found at


The advanced clinical evidence (ACE) report is a critical summary of the important details from a selected publication that assess both quality and the potential for bias. The report contains a synopsis of the publication, funding sources and implications, the principle research question, study groups, methods, outcome measures, important findings and their implications for the medical community. More information can be found at

Sliding hip screw versus the Targon PF nail in the treatment of trochanteric fractures of the hip: A randomised trial of 600 fractures J Bone Joint Surg Br. 2012 Mar;94(3):391-7. Level II – Randomized Trial

Quality of Evidence Score for this ACE Report: 7

Synopsis 598 patients (600 fractures) with trochanteric fractures of the hip were randomized to management using a sliding hip screw (SHS) or intramedullary nail to compare clinical outcomes. At 1 year followup clinical results were comparable between the two groups. The most notable difference was a significantly better improvement in mobility in the intramedullary nailing group.

Why Was This Study Needed Now? The treatment of trochanteric fractures has most commonly done using the sliding hip screw implant. Since its introduction in the 1980 intramedullary nailing has become more popular, however comparisons have indicated no differences between groups. New advances in intramedullary nailing treatment methods may result in superior clinical outcomes and a comparison re-evaluating the two treatment methods is required.

What Was The Principle Research Question? Does intramedullary nailing provide superior clinical results for patients undergoing the repair of trochanteric fractures of the hip when compared to sliding hip screw implants?

What Where The Important Findings?  There were no differences in total length of hospital stay, general medical complications or wound healing complications between groups  Shortening, loss of hip flexion and mortality rates were similar between groups  Intramedullary nailing resulted in significantly better mobility at 1 year follow-up (p=0.01)  There were no differences in residual pain between groups at any follow-up time point, at one year the Charnley pain score was 1.8 for the SHS and 1.6 for the Targon PF group (p>0.05) Intramedullary nailing provides better recovery of mobility for trochanteric hip fractures. OrthoEvidence Advanced Clinical Evidence Report. In: Ortho Evidence. Created Oct 01, 2011. Last modified Oct 01, 2012. Retrieved Dec 14, 2012 from *Details about the Quality of Evidence Score for this ACE Report can be found at

Meetings & ISFR Member Publications Recent ISFR Member Publications

Orthopaedic Research Society January 26-29, 2013 San Antonio, Texas

Prognostic Factors for predicting outcomes after intramedullary nailing of the tibia. Schemitsch E,

American Academy of Orthopaedic Surgeons March 19-23, 2013 Chicago, Illinois ISFR Board Meeting (at AAOS) March 21st, 2013 Chicago, Illinois

(Sample) size matters! An examination of sample size from the SPRINT trial. Bhandari M, Tornetta P, Rampersad S, Sprague S, Sanders DW< Schemitsch E, Swiontkowski M, Walter S. J Orthop Trauma 2012 June.

The need to standardize functional outcome in randomized trials of hip fracture: A review using the ICF framework. Hoang-Kim A, Beaton D, Bhandari M, Kulkarni AV, Schemitsch E, J Orthop Trauma 2012 Apr 24.

IOF-ECCEO 13 April 17-20, 2013 Rome, Italy

An emerging cell-based strategy in orthopaedics: endothelial progenitor cells. Atesok K, Matsumoto T, Karlsson J, et al. Knee Surg Sports Traumatol Arthrosc. 2012 Mar 9.

European Calcified Tissue Society May 18-21, 2013 Lisbon, Portugal

A preliminary study of platelet activation after embolization of marrow contents. Blankstein M, Byrick RJ, Nakane M et al. J Orthop Trauma 2012 Apr 2.

Failure strength of human vertebrae: Prediction using bone mineral density measured by DXA and bone volume by micro-CT. Perilli E, Briggs AM, Kantor S et al.

Canadian Orthopaedic Association June 20-22, 2013 Winnipeg, Canada

Bone 2012 Mar 10.

Shoulder arthroplasty in alkaptonuric arthropathy: a clinical case-report and literature review. Merolla G,

European Congress of Rheumatology (EULAR) June 12-15, 2013 Madrid, Spain European Federation (EFORT) June 5-8, 2103 Istanbul, Turkey

Bhandari M, Guyatt G, Sanders DW, Swiontkowski M, Tornetta P, Stephen D, Zdero R, Goslings JC, Teague D et al. J Bone and Joint Surgery 2012 October 3.



Dave AC, Pegreffi F et al. Musculoskeletal Surg 2012 Mar 24.

Implications for fracture healing of current and new osteoporosis treatments: An ESCEO Consensus paper. Goldhahn J, Feron JM, Kanis J, et al. Calcif Tissue Int 2012 90 (5): 343-53.

Comparison of 4 fluoroscopic views for dorsal cortex screw penetration after volar plating of the distal radius. Ozer K, Wolf JM, Watkins B et al. J Hand Surg Am 2012 Apr 4.

Inhibition of sclerostin by systemic treatment with sclerostin antibody enhances healing of proximal tibial defects in ovariectomized rats. McDonald MM, Morse A, Mikulec K et al. J Orthop Res 2012 Mar 27. doi:10.1002/ jor.22109.

ISFR Newsletter January 2013 Issue Editor-in-Chief: Alan Johnstone (UK) Associate Editor: Amy Hoang-Kim (Canada) Managing Editor: Carol Carnegie (UK) Contributors (listed in Alphabetical Order): Mohit Bhandari (Canada), Noriko Hasada (Japan), International Osteoporosis Foundation, Yohei Kawakami (Japan), Takashi Matsushita (Japan), Mehran Moazen (UK) Kenji Tobita (Japan), Yoshinobu Watanabe (Japan)

Contact Amy Hoang-Kim at on how to get more involved with ISFR activities, visit our website or follow us on Twitter, where you can find useful links to ongoing events & society updates and to re-connect and keep up with colleagues and ISFR board alumni, join us on Facebook

If you would like to have a news item or a research or education award announcement placed in the ISFR Newsletter please forward it by e-mail to Carol Carnegie,

Newsletter Jan 2013  

Regular newsletter from ISFR