Heterotopic Ossification Following Arthroplasty for Femoral Neck Fracture

Abstract

Background:

Heterotopic ossification (HO) is a frequent complication following hip surgery. Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we aimed to (1) determine the prevalence of HO following total hip arthroplasty (THA) for femoral neck fracture in patients ≥50 years of age, (2) identify whether HO is associated with an increased risk of revision surgery within 24 months after the fracture, and (3) determine the impact of HO on functional outcomes.

Methods:

We performed a multivariable Cox regression analysis using revision surgery as the dependent variable and HO as the independent variable. We compared Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores between participants with and those without HO at 24 months.

Results:

Of 1,441 participants in the study, 287 (19.9%) developed HO within 24 months. HO was not associated with subsequent revision surgery. Grade-III HO was associated with statistically significant and clinically relevant deterioration in the total WOMAC score, which was mainly related to the function component of the score, compared with grade I or II.

Conclusions:

The impact of grade-III HO on the functional outcomes and quality of life after THA for hip fracture is clinically important, and HO prophylaxis for selected high-risk patients may be appropriate.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Heterotopic ossification (HO) is the most frequent complication following primary total hip arthroplasty (THA). The reported frequency ranges from 5% to 87%, with an overall estimated prevalence of 30% to 40%^1–4. It has been previously proposed that only severe HO alters the clinical course^5–7. While severe HO is inarguably associated with a decreased range of motion⁵, disagreements persist regarding how this translates into functional outcomes^8–10. Traditional risk factors and clinical outcomes following the development of HO have been determined mostly from studies of primary arthroplasty procedures for arthritis. Whether HO alters the outcomes of THA or hemiarthroplasty (HA) for femoral neck fracture to the same extent is uncertain.

Many authors have validated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for prophylaxis in populations undergoing elective hip surgery^11–13. Recently, the use of aspirin as prophylaxis against venous thromboembolism has been suggested as an effective preventive measure against HO^14–16, which would eliminate the need for other NSAIDs. The hip fracture population is relatively frail, older, and less fit to undergo unexpected surgery. The liberal use of NSAIDs in this population is not benign, and functional benefits from HO prophylaxis have not been clearly defined; therefore, appropriate patient selection for prevention is warranted.

Using data collected as part of the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial (ClinicalTrials.gov NCT00556842)^17,18, we sought to better define HO following hip arthroplasty for hip fractures. HEALTH is a multicenter randomized controlled trial comparing THA and HA for the treatment of low-energy, isolated, displaced femoral neck fractures in patients ≥50 years old¹⁸. That trial was designed to evaluate the need for a secondary hip procedure within 24 months after the arthroplasty. In the present preplanned secondary analysis, we aimed to examine the prevalence of HO in this population, identify whether HO is associated with an increased risk of revision, and quantify the influence of HO on patients’ functional outcomes.

Materials and Methods

HEALTH Study Overview

Patients ≥50 years old presenting with an isolated, low-energy, displaced femoral neck fracture were enrolled at 80 participating sites in 10 countries and randomized to undergo THA or HA. Of the 1,495 patients in the HEALTH study, 1,441 (718 THAs and 723 HAs) were included in this secondary analysis. Participants were assessed clinically at 1 week, 10 weeks, and 6, 9, 12, 18, and 24 months postoperatively. The HEALTH trial was approved by the McMaster University Research Ethics Board (#06–151) and by the research ethics boards/institutional review boards of all participating clinical sites. The trial protocol and results have been published previously^17,18.

HO Evaluation

After each participant had completed their 24-month follow-up, the central adjudication committee consisting of 3 orthopaedic surgeons, including a chair, reviewed all available radiographs from scheduled and unscheduled clinical visits to identify the presence of HO. The chair independently reviewed all available radiographs for each participant who was identified as having HO and classified the severity of the HO according to the system developed by Brooker and colleagues (see Appendix A)⁹. We chose to use the Brooker classification (with the addition of grade 0 defined as the absence of HO) as it is the most widely used radiographic classification system for HO around the hip following THA or HA¹. All reviewers were blinded to clinical and functional outcomes. Given the poor interobserver and intraobserver reliability of the Brooker classification, Della Valle et al.¹⁹ suggested minimizing this source of discrepancy by pooling grades 0, I, and II to define low-severity HO and grades III and IV to define high-severity HO^19,20.

Statistical Analysis

The primary outcome measure in this analysis was the cumulative incidence of HO during the 24-month follow-up period. Additionally, we performed a multivariable Cox regression analysis to assess the impact of HO (the time-varying independent variable) on the risk of a revision procedure being performed within 24 months after fracture (the dependent variable). This analysis was adjusted for the following potential confounders: age, prefracture living status (institutionalized versus not institutionalized), prefracture ambulatory status (use of an assistive device to walk versus the ability to walk without an assistive device), American Society of Anesthesiologists (ASA) class (I/II versus III/IV/V), and type of arthroplasty (HA versus THA). After ensuring that the proportionality assumption was met, results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). All tests were 2-tailed with alpha = 0.05.

Hip Function Assessment

Using repeated-measures models for a 2-level independent analysis, we estimated the effect of HO on function, pain, and joint stiffness as measured with the self-administered Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire (the dependent variable). With higher scores representing worse pain, stiffness, and function^21,22, the ranges for the WOMAC dimensions are 0 to 20 for pain, 0 to 8 for stiffness, and 0 to 68 for physical function²¹. Patients were entered as random effects, while the presence and classification of HO at all visits (1 week, 10 weeks, and 6, 9, 12, 18, and 24 months) were included as time-varying independent variables in fixed effects. We included preinjury WOMAC scores as an adjustment variable. An autoregressive correlation structure was used to inform the model that each patient observation was expected to be correlated with its previous observation. Generalized linear models were created with Gaussian distributions. A threshold for the minimal clinically important difference (MCID) was set at 7 points based on previous literature^23,24. The results of the THAs and HAs were pooled as our original study showed that THA provided a clinically unimportant improvement in function and quality of life when compared with HA¹⁸. Results were reported as adjusted mean differences (AMDs) with 99% CIs. All tests were 2-tailed with alpha = 0.01.

Results

Cumulative Incidence of Heterotopic Ossification

Of 1,441 patients (718 randomized to THA and 723 randomized to HA as part of the HEALTH trial) included in our analysis, 287 (19.9%) developed HO (Table I). Only 63 (4.4%) of the 1,441 patients developed high-grade (Brooker grade-III or IV) HO. The majority (218; 76.0%) of the 287 patients with HO had evidence of it on radiographs by 10 weeks postoperatively.

TABLE I.

Timing of Heterotopic Ossification Diagnosis After Fracture Surgery by Brooker Classification

Follow-up	Brooker Classification (no. [%])
	I	II	III	IV	Total
1 week	0 (0.0)	1 (0.3)	1 (0.3)	0 (0.0)	2 (0.7)
10 weeks	99 (34.5)	99 (34.5)	20 (7.0)	0 (0.0)	218 (76.0)
6 months	93 (32.4)	110 (38.3)	22 (7.7)	0 (0.0)	225 (78.4)
9 months	90 (31.4)	112 (39.0)	25 (8.7)	0 (0.0)	227 (79.1)
12 months	72 (25.1)	144 (50.2)	41 (14.3)	3 (1.0)	260 (90.6)
18 months	72 (25.1)	164 (57.1)	41 (14.3)	3 (1.0)	280 (97.6)
24 months	55 (19.2)	169 (58.9)	58 (20.2)	5 (1.7)	287 (100.0)

HO and the Risk of Revision Surgery

Of the 1,441 patients, 1,426 had sufficient data at 24 months for this analysis. Overall, there were 116 events of unplanned secondary procedures; however, none were performed for excision of HO. In the multivariable analysis, the diagnosis of HO was not associated with a higher risk of arthroplasty revision within 24 months after the femoral neck fracture (p = 0.70) (Table II).

TABLE II.

Association Between Heterotopic Ossification and Revision Surgery 24 Months Post-Fracture (N = 1,426; 116 Events)

Independent Variable	HR (95% CI)	P Value
Heterotopic ossification: yes versus no	0.92 (0.58, 1.44)	0.70
Age	0.99 (0.97, 1.02)	0.52
Prefracture living status: institutionalized versus not institutionalized	0.93 (0.34, 2.54)	0.88
Independent ambulation: yes versus no (any aid used)	1.29 (0.84, 1.98)	0.25
ASA class: III/IV/V versus I/II	0.93 (0.64, 1.36)	0.70
Implant received: total hip arthroplasty versus hemiarthroplasty	0.95 (0.66, 1.37)	0.78

Hip Function Assessment

Having low-grade HO (grade I or II) as compared with having no HO was not associated with a significantly higher mean total WOMAC score (Table III and Appendix B). Having high-grade HO (grade III or IV) as compared with no HO was associated with a significantly higher mean WOMAC total score (AMD = 8.23, 99% CI = 0.56 to 15.89; p = 0.006), indicating worse overall hip function (see Appendix C). Patients with high-grade HO (grade III or IV) as compared with the no-HO and low-grade-HO groups combined (grade 0, I, or II) had a significantly higher mean WOMAC total score (AMD = 8.66, 99% CI = 1.06 to 16.27; p = 0.003), WOMAC pain score (AMD = 1.54, 99% CI = 0.10 to 2.98; p = 0.006), and WOMAC functional score (AMD = 6.21, 99% CI = 0.26 to 12.16; p = 0.007), indicating worse function and pain at 24 months post-fracture (see Appendix D). However, only the AMD for the WOMAC total scores reached the MCID threshold of 7.

TABLE III.

WOMAC Scores at 24 Months According to Brooker Classification of Heterotopic Ossification

WOMAC Score†	Adjusted Mean Difference in Score at 24 Months (99% CI)*
	Class 0 vs. Class I/II (N = 1,154)	Class 0 vs. Class III/IV (N = 1,218)	Class 0/I/II vs. Class III/IV (N = 1,441)
Total	−1.54 (−5.73 to 2.65)	8.23 (0.56 to 15.89)‡	8.66 (1.06 to 16.27)‡
Pain	−0.48 (−1.26 to 0.30)	1.46 (−0.06 to 2.97)	1.54 (0.10 to 2.98)‡
Stiffness	0.09 (−0.31 to 0.49)	0.51 (−0.22 to 1.24)	0.49 (−0.23 to 1.21)
Function	−1.26 (−4.55 to 2.03)	5.81 (−0.16 to 11.78)	6.21 (0.26 to 12.16)‡

^*The mean difference was adjusted for baseline scores and obtained from the multilevel model.

^†The minimal clinically important difference (MCID) was set at 7 points for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

^‡P < 0.01.

Grade-III HO was found to be associated with a clinically relevant and statistically significant deterioration in the WOMAC total score (AMD = 11.40, 99% CI = 2.18 to 20.61; p = 0.002) and function score (AMD = 8.41, 99% CI = 1.48 to 15.36; p = 0.002) as compared with low-severity HO (grade I or II) (Table IV and Appendix E). Following the same trend, high-grade HO (III or IV) was associated with a significantly worse WOMAC total score (AMD = 10.77, 99% CI = 1.70 to 16.63; p = 0.002) and function score (AMD = 7.95, 99% CI = 1.13 to 14.76; p = 0.003) compared with low-grade HO (I or II), with both score increases reaching the MCID (Table IV and Appendix F). Specifically, from the patient’s perspective^25,26, having low-severity HO (grade I or II) was not associated with a clinically important deterioration in functional outcome; however, grade-III HO was associated with a significant and clinically meaningful deterioration in function without affecting pain or joint stiffness.

TABLE IV.

Comparison of WOMAC Scores at 24 Months Between Low and High-Severity Heterotopic Ossification According to Brooker Classification

WOMAC Score†	Adjusted Mean Difference in Score at 24 Months (99% CI)*
	Class I/II vs. Class III (N = 282)	Class I/II vs. Class III/IV (N = 287)
Total	11.40 (2.18 to 20.61)‡	10.77 (1.70 to 16.63)‡
Pain	2.15 (0.43 to 3.86)‡	2.06 (0.38 to 3.75)‡
Stiffness	0.46 (−0.39 to 1.30)	0.41 (−0.42 to 1.25)
Function	8.41 (1.48 to 15.36)‡	7.95 (1.13 to 14.76)‡

^*The mean difference was adjusted for baseline scores and obtained from the multilevel model.

^†The minimal clinically important difference (MCID) was set at 7 points for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

^‡P < 0.01.

Discussion

Using prospectively collected data from the HEALTH trial, we investigated the prevalence of HO following arthroplasty for hip fractures as well as the risk of revision surgery and the functional outcomes associated with this condition. Our findings confirm that the development of HO following THA or HA for a femoral neck fracture is fairly common, although the prevalence of 19.9% for any grade of HO at 24 months postoperatively in our study is lower than that in previous reports, in which the prevalence has usually ranged from 27.9% to 86.9%^27–38. The prevalence of severe HO (grade III or IV) was 4.4% (63 of 1,441) in our study, in which only 5 patients (0.35%) had hip ankylosis (grade IV), which is similar to the previously reported prevalence of 3.6% to 7% for grades-III and IV HO following THA or HA^3,39–41. Considering the broad demographic features and the prospective nature of our study, we believe that it is likely representative of the prevalence of this complication in patients ≥50 years old in whom an isolated femoral neck fracture is treated by arthroplasty.

Revision surgery for HO is exceedingly rare, with reported rates of 0% to 0.40%^{8,35,40,42,43} and most of the procedures done for severely ankylosed hips (Brooker grade IV). In a consecutive series of 1,482 THAs, Alijanipour et al.⁴⁰ reported no revision surgery for excision of HO. Similarly, Gofton et al.⁴² noted only 2 revision procedures for HO in their 10-year retrospective review of 1,087 primary THAs, in which the 2 patients were the only ones with grade-IV HO. This is consistent with our 0% revision rate for excision of HO and suggests that, even though we found an association between HO and hip-related reduction in functional outcomes, patients with HO following arthroplasty for a hip fracture are not necessarily more likely to require revision surgery.

Currently, it is generally accepted that low-grade HO (Brooker grades I and II) is not clinically relevant, which is consistent with our results²⁰. In contrast, there are considerable conflicting data regarding the clinical relevance of Brooker grade-III or IV HO. Several authors have found reduced walking ability, function, and range of motion (especially flexion)^{5,20,33,38,44,45} in patients with grade-III or IV HO, without an effect on pain scores^5,8,20,33,38. A meta-analysis by Neal⁵ showed Brooker grade-III and IV HO to have a negative correlation with range of motion and functional outcomes, whereas some authors concluded that only very severe HO (Brooker grade IV) is clinically relevant^6,7,9. In a study of 507 consecutive patients, Morrey et al.⁶ found a decreased arc of motion only in those affected by grade-IV HO and no statistically significant difference in functional outcomes or pain scores among all grades. Similarly, a prospective randomized study demonstrated no significant difference in outcomes among all of the Brooker grades with the exception of grade IV⁷. Although authors of previous reports have hypothesized that only grade IV is clinically relevant, the results of our study have shown that patients with grade-III HO report a clinically meaningful deterioration in overall function compared with those with lower-severity HO (grades I and II), and this is not explained by increased pain or stiffness.

The results of this study have to be interpreted with caution since the sample-size calculation was based on a comparison of THA and HA with a primary outcome of unplanned secondary procedures, not on secondary outcomes such as HO¹⁷. Also, grade-IV HO is exceedingly rare and was widely underrepresented in our study; thus, the comparison of the pooled results associated with grades III and IV may reflect functional outcomes and quality of life mostly related to grade III with very little contribution from grade IV.

To the best of our knowledge, this is the largest study reporting the prevalence of HO after arthroplasty in the setting of hip fractures. Fortunately, the prevalence of hip ankylosis (HO grade IV) remains rare. Additionally, our results demonstrate that grade-III HO is associated with worse functional outcomes; therefore, prophylaxis with acetylsalicylic acid or other NSAIDs may be recommended for carefully selected high-risk patients.

Appendix

Supporting material provided by the authors is posted with the online version of this article as a data supplement at jbjs.org (http://links.lww.com/XXXXXXX).

Note:

The HEALTH Investigators include:

Writing Committee: Mohit Bhandari (Chair, McMaster University), Thomas A. Einhorn (New York University Langone Medical Center), Gordon H. Guyatt (McMaster University), Emil H. Schemitsch (University of Western Ontario), Robert D. Zura (Louisiana State University Health Sciences Center), Sheila Sprague (McMaster University), Frede Frihagen (Oslo University Hospital), Ernesto Guerra-Farfán (Hospital Vall d’Hebrón), Ydo V. Kleinlugtenbelt (Deventer Ziekenhuis), Rudolf W. Poolman (OLVG), Amar Rangan (The James Cook University Hospital), Sofia Bzovsky (McMaster University), Diane Heels-Ansdell (McMaster University), Lehana Thabane (McMaster University), Stephen D. Walter (McMaster University), P.J. Devereaux (Co-Chair, McMaster University).

Steering Committee: Mohit Bhandari (Chair, McMaster University), P.J. Devereaux (McMaster University), Thomas A. Einhorn (New York University Langone Medical Center), Frede Frihagen (Oslo University Hospital), Ernesto Guerra-Farfán (Hospital Vall d’Hebrón), Kenneth J. Koval (Orlando Regional Medical Centre), Rudolf W. Poolman (OLVG), Emil H. Schemitsch (University of Western Ontario), Kevin Tetsworth (University of Queensland), Lehana Thabane (McMaster University), Stephen D. Walter (McMaster University), Gordon H. Guyatt (McMaster University).

Global Methods Centre: Mohit Bhandari (Principal Investigator), Sheila Sprague (Research Director), Paula McKay (Manager); Kim Madden, Sofia Bzovsky, Kerry Tai, Taryn Scott, Marilyn Swinton (Research Coordination), Naveen Khan (Adjudication Coordination), Diane Heels-Ansdell (Statistical Analysis), Lisa Buckingham, Aravin Duraikannan (Data Management);, (McMaster University).

United States Methods Centre: Thomas A. Einhorn (Principal Investigator), Heather Silva (Research Coordination) (Boston University Medical Center). Thomas A. Einhorn, David Novikov, Daniel P. Waren (New York University).

Netherlands Methods Centre: Ydo V. Kleinlugtenbelt, Ellie B.M. Landman (Deventer Ziekenhuis; Definitive). Martin J. Heetveld, Rudolf W. Poolman, Esther M.M. Van Lieshout, Paul T.P.W. Burgers (Erasmus MC, University Medical Center Rotterdam, Rotterdam; Pilot).

United Kingdom Methods Centre: Amar Rangan (The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, University of Oxford, University of York), Birgit Hanusch, Lucksy Kottam (The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust).

Central Adjudication Committee: Robert D. Zura (Chair, Louisiana State University Health Sciences Center), Victoria Avram (McMaster University), Ajay Manjoo (McMaster University).

Data and Safety Monitoring Board (CIHR): John Antoniou (Chair), Tim Ramsay, Earl R. Bogoch, Andrew Trenholm.

Data and Safety Monitoring Board (NIH): Stephen Lyman (Chair), Madhu Mazumdar, Kevin J. Bozic, Mark Luborsky, Stuart Goodman, Susan Muray, Benjamin K. Potter.

Statistical Support: Diane Heels-Ansdell, Lehana Thabane, Nathan N. O’Hara, Gerard P. Slobogean, Quazi Ibrahim.

Participating Clinical Sites:

Canada:

University of Calgary – Richard Buckley, Robert Korley, Paul Duffy, Shannon Puloski, Eldridge Batuyong, Christopher Martin, James MacKenzie, Jason Werle, Kelly Johnston, Neil White, Marcia Clark, Gregory Abelseth, Stephen Hunt, Justin LeBlanc, Prism Schneider, Kimberly Carcary, Ross McKercher, Lisa Murphy, Melissa Lorenzo, Tanja Harrison, Leah Schultz, Aftab Akbari, Stephanie Yee, Tina Samuel, Saboura Mahdavi.

University of British Columbia/Fraser Health Authority/Royal Columbian Hospital – Trevor B. Stone, Bertrand Perey, Farhad Moola, Darius Viskontas, Kelly Apostle, Dory Boyer, H. Michael Lemke, Robert McCormack, Mauri Zomar, Bindu Mohan, Karyn Moon, Raely Pritchard, Brenda Chen Fan, Kyrsten Payne.

St. Michael’s Hospital – Aaron Nauth, Emil H. Schemitsch, Michael D. McKee, Jeremy A. Hall, Daniel Whelan, Sarah Ward, David Walmsley, Earl R. Bogoch, James P. Waddell, Henry Ahn, Timothy R. Daniels, Milena R. Vicente, Jennifer T. Hidy, Melanie T. MacNevin, Paril Suthar.

Sunnybrook Health Sciences Centre – Hans Kreder, David Stephen, Richard Jenkinson, Markku Nousiainen, Terry Axelrod, Veronica Wadey, Sebastian Tomescu, Monica Kunz, Katrine Milner, Melanie MacNevin, Ria De Gorter (Cagaanan), Wesley Ghent, Fathima Adamsahib, Araby Sivananthan, Aimee Theriault, Michelle Arakgi, Phumeena Balasuberamaniam, Ravi Tuazon.

Vancouver General Hospital – Peter J. O’Brien, Piotr A. Blachut, Henry M. Broekhuyse, Pierre Guy, Kelly A. Lefaivre, Gerard P. Slobogean, Dean G. Malish, Raman Johal, Jessica Peattie, Abdullah Mamun, Benita Okocha, Irene Leung.

Hôpital de l’Enfant-Jésus – Étienne Belzile, Luc Bedard, Martin Bédard, Bernard Laliberté, Jean Lamontagne, Martin Lesieur, Luc Petitclerc, Marie-ève Roger, Stéphane Pelet, Luc Lemire, Hélène Côté.

Queen Elizabeth II Health Sciences Centre – Chad Coles, Ross Leighton, C. Glen Richardson, Michael Biddulph, Michael Gross, Michael Dunbar, J. David Amirault, David Alexander, Catherine Coady, Mark Glazebrook, David Johnston, William Oxner, Gerald Reardon, Ivan Wong, Kelly Trask, Shelley MacDonald.

Memorial University of Newfoundland – Andrew Furey, Craig Stone, Keegan Au, William Moores, Peter Rockwood, Carl Moores, Daniel Squire, Sarah Anthony, Minnie Parsons, Valisha Keough, Erin Baker.

Lakeridge Health – Samir Chhabra, Osama Gharsaa, Abdulmajid Ibrahim, Esmat Dessouki, Omar Dessouki, Aileen Manganaro, Kelly Fusco.

Hôpital Saint-François d’Assise – François Marquis, Annie Arteau, Marc Bouchard, Alexandre Leclerc, Michèle Angers, Sylvain Belzile, Sylvie Turmel

Hôpital du Sacré-Coeur de Montréal – G.-Yves Laflamme, Benoit Benoit, Pierre Ranger, Michel Malo, Julio Fernandes, Julie Fournier, Karine Tardif.

Ottawa Hospital Research Institute, The Ottawa Hospital – Robert J. Feibel, Hesham Abdelbary, Christopher Kennedy, Paul Kim, Paul Beaule, Joel Werier, Alberto Carli, Peter Lapner, Geoff Dervin, Katie McIlquham, Sara A. Ruggiero, Carly St. Germain, Heather Cosgrove, Johanna Dobransky, Cheryl Kreviazuk.

Humber River Hospital – Sebastian Rodriguez-Elizalde, Anna Rose Soliman, Sagar Desai, John Townley, Iriss Mariano, Theresa B. Pedutem, Mary June Francisco.

United States:

Lahey Hospital and Medical Center – Andrew Marcantonio, Michael Kain, Lawrence Specht, John Tilzey, John Garfi.

Mayo Clinic – Andrew Sems, Tab Mabry, Joseph Cass, Michael Torchia, William Cross, Michael Taunton, Joaquin Sanchez-Sotelo, Rafael Sierra, Barbara Foreman.

Marshall University – Franklin D. Shuler, James Day, Tigran Garabekyan, Felix Cheung, Ali Oliashirazi, Jonathon Salava, Linda Morgan, Timothy Wilson-Byrne, Grant Buchanan, Milad Modarresi, Mary Beth Cordle.

Indiana University – Brian Mullis, Karl Shively, Andrew Parr, Janos Ertl, Ripley Worman, Mark Webster, Judd Cummings, Valda Frizzell, Molly Moore.

New York University – Thomas A. Einhorn, Kenneth A. Egol, Nirmal C. Tejwani, Roy I. Davidovitch, Ran Schwarzkopf, Jonathan M. Vigdorchik, James D. Slover, Sanjit R. Konda, Toni M. McLaurin, David Novikov, Pankajkumar Patel, Daniel P. Waren.

Orthopaedic Associates of Michigan – Clifford B. Jones, James R. Ringler, Debra L. Sietsema.

University Orthopaedic Associates – Carlos Sagebien, David Harwood, Stephen Kayiaros, Patricia Seuffert.

The CORE Institute – Clifford B. Jones, Russell Meldrum, Sarim S. Ahmed, Debra L. Sietsema.

Texas Tech University – Enes Kanlic, Amr Abdelgawad, Juan Shunia.

University of Pennsylvania – Samir Mehta, John L. Esterhai Jr., Jaimo Ahn, Derek Donegan, Atul Kamath, Neil Sheth, Annamarie Horan, Patrick Hesketh, Thomas Rose.

Duke University Medical Center – Rachel Reilly, Robert D. Zura, Steven Olson, Kendra Marr, Maria Manson, Cameron Howes.

University of Mississippi Medical Center – Benjamin M. Stronach, Patrick F. Bergin, Jennifer S. Barr, Clay A. Spitler, Josie M. Hydrick, Leslie N. Johnson.

Boston University Medical Center – Thomas A. Einhorn, Paul Tornetta III, William R. Creevy, Heather Silva, Michelle J. Lespasio, Hope Carlisle.

Colorado Orthopedic Consultants – Craig Davis, Philip Stull, Stewart Weinerman, Peter Weingarten, Steven Lindenbaum, Michael Hewitt, Rebecca Danielwicz, Janell Baker.

Mission Hospital Research Institute – Charles DePaolo, Christina Riggsbee, Tracey Nanney.

Park Nicollet Institute – Gregg Strathy, Kathleen Peter, Paul Johnson, Meaghan Morton.

Rubin Institute for Advanced Orthopaedics – Michael Mont, Donald E. Delanois, Bhaveen Kapadia, Kimona Issa, Marylou Mullen.

SUNY Buffalo – Mark Anders, Christopher Mutty, Matthew Phillips, Sridhar Rachala, Mary Bayers-Thering.

Allegheny – Timothy J. Sauber, Edward Westrick, Joseph Guth, Michael H. Maher.

University of Utah – Thomas F. Higgins, Erik N. Kubiak, Jeremy Gililland, David Rothberg, Christopher Peters, Christopher Pelt, Ami R. Stuart, Kirby Corbey, Ashley Neese, Mark T. Russell, Victor Solis, Andrea Gurule.

University of California Irvine – David Zamorano, John A. Scolaro, Douglas Kiester, Deeba Pourmand.

St. Elizabeth Youngstown Hospital – Tyson T. Schrickel, John V. Gentile, Barbara M. Hileman, Elisha A. Chance.

Rothman Institute – Javad Parvizi, Tiffany Morrison.

Emory University School of Medicine – James Roberson, Thomas Bradbury, Greg Erens, Kyle Webb.

University of Arizona – Michael Dohm, Cindy Fastje, José Luis Camarena, Maria Gordon.

The Netherlands:

Deventer Ziekenhuis – Ydo V. Kleinlugtenbelt, Hans-Peter W. van Jonbergen, Willem H. Roerdink, Joost M. Reuver, Alexander F.W. Barnaart, Elvira R. Flikweert, Danielle D. Langeloo, Rinco C.T. Koorevaar, Hannie H.F. Elskamp-Meijerman, Ellie B.M. Landman.

Amphia Ziekenhuis – Leon H.G.J. Elmans, Joost A.A.M. van den Hout, Adrianus J.P. Joosten, Ad F.A. van Beurden, Stefan B.T. Bolder, Denise Eygendaal, Adrianus F.C.M. Moonen, Rutger C.I. van Geenen, Eric A. Hoebink, Robert Wagenmakers, Wouter van Helden.

Tergooiziekenhuizen – Harm M. van der Vis, Lijkele Beimers, Jasper de Vries, Arthur W. Zurcher, G.H. Rob Albers, Maarten Rademakers, Stefan Breugem, Ibo van der Haven, Pieter Jan Damen, Gythe H. Bulstra, Martin M. Campo, Mathijs P. Somford, Daniël Haverkamp.

OLVG – Rudolf W. Poolman, Bauke W. Kooistra, Willem Jan Kleyn Molekamp, Frank R.A.J. de Meulemeester, Arthur E.B. Kleipool, Robert Haverlag, Maarten P. Simons, Eduard L.A.R. Mutsaerts, Diederik H.R. Kempen, Mark C. Altena, Dirk Jan F. Moojen, John (S.J.) Ham, Arnard van der Zwan, Derek F.P. van Deurzen, Michel P.J. van den Bekerom, Vanessa A.B. Scholtes, Mariëlla E.M. Volkers, Amanda D. Klaassen, Loes W.A.H. van Beers, Nienke W. Willigenburg, Ihsan Amajjar, Joint Research Group.

Isala Clinic – Sven H. van Helden, R.G. Zuurmond, Adriaan Mostert, P. Houben, G. Solinge, W.R. Spanjersberg, R. Nijveldt, K. van Egmond, Lonneke Buitenhuis.

Gelre Ziekenhuizen – Hugo W. Bolhuis, Pieter H.J. Bullens, Mike Hogervorst, Karin E. de Kroon, Rob H. Jansen, Ferry Steenstra, Eric E.J. Raven.

Spaarne Ziekenhuis – Peter A. Nolte, Michel P.J. van den Bekerom, Tjitte de Jong, Arthur van Noort, Diederik A. Vergroesen, Bernard G. Schutte.

Diaconessenhuis Leiden – Rover Krips, J. Bernard Mullers, Hans Schüller.

Medisch Centrum Haaglanden – Stefan B. Keizer, Jan-Willem A. Swen, Peter H.C. den Hollander, Bregje J.W. Thomassen.

IJsselland Ziekenhuis – W. Peter J. Fontijne, Saskia C. Wiersma, Bastiaan Boetes, Edgar J.T. ten Holder.

Ruwaard van Putten Ziekenhuis – Rob Kooijman, Roelf R. Postema, René J.T.M. Bleker, Harald I.H. Lampe.

Slotervaartziekenhuis – Lein Schuman, John Cheung, Frank van Bommel, W. Paul C.A. Winia, Daniel Haverkamp, Harm van der Vis.

Leids Universitair Medisch Centrum – Huub J.L. van der Heide, Jochem Nagels, Enrike H.M.J. van der Linden-van der Zwaag.

Gelderse Vallei – Jan P. van Dijk, Wouter H. van Helden.

Flevoziekenhuis – Mark L.M. Falke, Frans J. Kurek, Adrianus C.H. Slingerland.

Spain:

Hospital Vall d’Hebrón – Ernesto Guerra Farfán, Jordi Teixidor Serra, Jordi Tomás Hernández, Vicente Molero García, Jordi Selga Marsà, Juan Antonio Porcel Vázquez, Joan Minguell Monyart, Maria Villar Casares, Jaume Mestre Torres, Sandra Ponce Ruiz, Teresa Sanclemente Boli, Judith Sánchez-Raya, José Andrés Peiró, Diego Collado Gastalver, Víctor Barro Ojeda, Iñaki Mimendia Sancho, Maria Jurado Ruiz, Carla Carbonell Rosell, M. Cristina García Martínez, Luken Zubizarreta Barrutia, Martí Plomer Sánchez, Felipe Moreira Borim, Jorge Nuñez Camarena, Antoni Fraguas Castany, Yaiza García Sánchez, Míriam Garrido Clua.

Hospital Universitari Mútua de Terrassa – Pablo Castillón, Martí Bernaus, Francesc Anglés, Agustí Bartra.

Hospital Dr. Josep Trueta – Miguel Angel Froufe Siota, Diana Noriego, Samer Al-dirra, Xavier Madirolas, Cristina Martinez Merchan.

Hospital Universitario Costa del Sol – Enrique Guerado, Encarnación Cruz, Juan Ramon Cano, Manuel Godino, Miguel Hirschfeld, Laura Ramos, Antonio Royo, Adolfo Galán, Paqui Fontalba, Pilar Gavira.

University Hospital 12 de Octubre – José A. Moreno-Beamud, Emilio Delgado-Diaz, Arantxa Capel-Agundez, Pedro Caba-Dousseaux, Rafael Navarro-Arribas.

Hospital Clinic de Barcelona – Oscar Ares, Jenaro A. Fernandez-Valencia, Alonso Zumbado, Pilar Camacho-Carrasco, Marta Gutierrez.

Norway:

Oslo University Hospital – Frede Frihagen, Lars Nordsletten, John Clarke-Jenssen, Geir Hjorthaug, Kaare Midtgaard, Lene B. Solberg, Carl Erik Alm, Jonas Rydinge, Marianne Westberg, Stephan Röhrl, Torben Ianssen, Knut Erik Mjaaland, Ole Christian Brun, Finnur Snorrason, Bernhard Flatøy Stian Svenøy, Elise Berg Vesterhus, Anne Christine Brekke, Sissel Knuts.

Ringerike Hospital – Ingunn Skaugrud, Engelke Randers.

United Kingdom:

Royal Cornwall Hospital – Manish Divekar, Palakkad Easwaran, Daniel Williams, Robin Kincaid, Shaun Sexton, Shyam Maimen, Rory Middleton, Gavin Bartlett, Fiona Hammonds, Benita Adams, Anna Fouracres, Jackie Dingle, Jessica Summers, Nicki Devooght-Johnson, Alyson Andrew, Abigail Weeks.

East Sussex Healthcare – Adrian Butler-Manuel, Oliver Keast-Butler, Guy Selmon, Andrew Armitage, Simon Pearce, Simon Hoskinson, Miranda Champion, Satish Ganesan, Manjunathan Sivaprakasam, Zaid Al-Wattar, Paul Cameron, Kate Weatherly, Kim Miles, Janet Sinclair.

Leicester Royal Infirmary – John Davison, Jonathon White, Andrew Brown, S. Subramanian, Jenny Nichols, Aujlia Randeep, Christina Haines, Manjit Attwal, Dileep Kumar, Debbie Lee, Mona Mohamed, Sharon Siddons.

Northumbria Healthcare – Dominic Inman, Mike Reed, Ajay Malviya, An Murty, Paul Partington, Ian Carluke, Derek Kramer, Kevin Emmerson, Scott Muller, David Townshend, Juhu Joseph, Jonathon Coorsh, Sameer Khan, Rajesh Kakwani, Helen Shirley, Kerry Third, Christine Dobb, Deborah Bunn, Chris Herriott, Elizabeth Corbishley, Gail Waddell.

Barts Health NHS Trust – Joshua Lee, Steve Millington, Stephen Key, Daud Chou, Alex Vris, Sammy Hanna, Anna Berridge, Jamila Kassam, Catherine Hilton, Shanaz Ahmad.

Cambridge University Hospital – Christopher Gooding, Wasim Khan, Stephen McDonnell, Peter Hull, Joseph Queally, Frances New, Simone Hargreaves, Debbie Read.

University Hospital of North Tees – Rajesh Nanda, Christopher Tullock, Rajnikanth Logishetty, Antoni Nargol, Richard Jeavons, Angela Bradbury, Carol Bowler, Janet Austin.

The James Cook University Hospital – Birgit Hanusch, Amar Rangan, Paul Baker, Anthony Hui, Craig White, Ian Wallace, Simon Jameson, James Webb, William Eardley, Lucksy Kottam, Alanna Milne, Juliet James.

Yeovil District Hospital – Matthew Hall, Roshan Raghavan, Benedict Lankester, Paul Latimer, Paul Porter, Istvan Batta, Alison Lewis, Lucy Pippard.

South Devon Healthcare – Gordon Higgins, Veronica Conboy, Yousef El-Houdiri, Steve Blake, David Isaac, Pauline Mercer.

Sherwood Forest Hospital – Sreebala C.M. Srinivasan, Sachin P. Badhe, Amit W. Bidwai, Rebecca Boulton, Sarah Shelton.

Australia:

University Hospital Geelong, Deakin University – Richard Page, Andrew Thomson, Simon Williams, Chatar Goyal, David Bainbridge, Richard Angliss, Ben Miller, Graeme Brown, Kevin Eng, David Bowyer, John Skelley, Glenn Boyce, Adam Watson, Nathan Donovan, Sally Beattie, Amanda Cowland.

The Alfred – Susan Liew, Harvinder Bedi, Ashley Carr, Andrew Chia, Steve Csongvay, Craig Donohue, Stephen Doig, Elton Edwards, Max Esser, Richard Freeman, Andrew Gong, Doug Li, Russell Miller, Lu Ton, Otis Wang, Ian Young, Ash Moaveni, Matthias Russ, Siva Chandrasekaran, Arvind Jain, Adam Dowrick, Zoe Murdoch, Claire Sage.

Prince Charles Hospital – Catherine McDougall, Sue Grice, Scott Crawford, Dinesh Sharma, Andrew Patten, Rebecca Ferrier.

Finland:

Turku University Hospital – Matti Seppänen, Mika Junnila, Jari Mokka, Kari Isotalo, Niko Strandberg, Jani Knifsund, Keijo Mäkelä, Keemu Hannes, Mikko Karvonen, Saara Meronen.

New Zealand:

North Shore Hospital – William Farrington, Rob Sharp, Otis Shirley, Luke Brunton, Marla Ross, Sherina Holland.

South Africa:

University of KwaZulu-Natal/Grey’s Hospital – Rian Smit, Leonard Marais, Simphiwe Gumede, Reitze Rodseth.