Abstract
Collaboration between military and civilian investigators is necessary to develop strategies for optimizing treatments to diminish the sequelae of non–battle-related musculoskeletal injuries, which are highly prevalent among servicemembers. The 2024 Extremity War Injuries Symposium provided a forum whereby a diverse group of clinicians and researchers could develop strategies for optimizing treatments and diminishing the sequelae of conditions that are highly prevalent among active individuals. Key points were as follows:
1. The value of collaborations between military and civilian investigators cannot be overemphasized. These synergies can leverage the capabilities of established infrastructures in order to answer important questions pertaining to short-term outcomes—for example, warrior readiness of anterior cruciate ligament reconstructions among servicemembers and long-term posttraumatic osteoarthritis (PTOA) outcomes among civilian cohorts.
2. Current and future prospective trials will inform future treatment decisions related to multiligamentous knee injuries and glenohumeral instability.
3. Novel approaches to addressing PTOA in the acute postinjury period will need longitudinal surveillance to measure their impact on improving clinical outcomes and diminishing residual functional deficits.
Since 2005, the Extremity War Injuries (EWI) Symposium has convened annually to bring clinicians, researchers, policy makers, and stakeholders together to identify the most conspicuous knowledge gaps related to musculoskeletal disease. Currently, musculoskeletal disease and nonbattle injuries (DNBIs) remain a preeminent threat to medical readiness among US servicemembers and a source of substantial health care–related costs. 20 Given this fact, recent EWI symposia, which have been cosponsored by the Society of Military Orthopaedic Surgeons (SOMOS), the American Orthopaedic Society for Sports Medicine (AOSSM), the Orthopaedic Trauma Association, and the American Society for Surgery of the Hand have focused on a number of injuries germane to sports medicine. EWI XVII convened in Washington, DC, on January 15-17, 2024, and the purpose of this summary is to report on the program's yield, highlight promising ongoing initiatives, and describe a way forward that leverages existing partnerships and stimulates new, multidisciplinary collaborations capable of enhancing the medical readiness and warfighter lethality of servicemembers.
The Promise of Military-Civilian Collaborations
Launched in 2016, the Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) has expanded to 15 military treatment facilities and represents a first-of-its-kind enterprise that exists as a repository for prospectively collected clinical data (patient-reported outcome measures, intraoperative surveys completed by surgeons) on over 15,000 patients. 15 As this database continues to mature, so too do its capabilities to better describe the burden of a myriad of injuries, answer meaningful clinical questions, and forecast the likelihood of servicemembers returning to full, unrestricted duty.
Equally promising are the emerging opportunities for collaborations between the MOTION enterprise and civilian research teams, and the recent collaboration between MOTION and the Multicenter Orthopaedic Outcomes Network (MOON) promises to make significant strides toward optimizing the treatment of servicemembers with anterior cruciate ligament (ACL) injuries. Supported by a Medical Technology Enterprise Consortium Award, MOTION and the MOON Knee Group are leveraging previously published predictive return-to-high-activity calculators to forecast the likelihood of servicemembers returning to full, unrestricted duty. This award is also facilitating efforts to obtain 20-year clinical follow-up on the MOON Knee cohort, which will inform current and future perspectives on long-term clinical outcomes of ACL reconstruction and identify the most significant risk factors for the development of posttraumatic osteoarthritis (PTOA). A similar collaboration between MOTION and the MOON Shoulder Group is now underway as well and promises to sharpen current understandings of return-to-play/return-to-duty forecasts for patients undergoing glenohumeral stabilization procedures as well as the risk factors for developing glenohumeral joint PTOA. The evolution of these military-civilian collaborations has brought a diverse group of clinicians together to leverage the capabilities of existing data sets and apply validated analytical methods across more robust cohorts.
Necessity of Prospective Clinical Trials: Current and Future
The value of military-civilian collaborations is seen in several other ongoing prospective clinical trials focused on multiple injury patterns commonly observed among servicemembers. Supported by a Peer Reviewed Orthopaedic Research Program (PRORP) award, the Surgical Timing and Rehabilitation Trial for Multiple Knee Ligament Injuries seeks to investigate the effects of the timing of surgery (early vs delayed) and timing of rehabilitation (early vs delayed) in patients undergoing multiligamentous knee injury (MLKI) reconstruction via 2 parallel randomized controlled trials. 18 Three military treatment facilities have participated in patient enrollment as part of a broader, 28-site effort, which represents the largest prospective interventional trial of its kind seeking to optimize the treatment of non–combat related and combat-related MLKI alike, the latter of which has been observed to be a substantial source of long-term disability among servicemembers. 2
Similarly, the Open Versus Arthroscopic Stabilization of Shoulder Instability with Subcritical Bone Loss (OASIS) Trial seeks to answer important clinical questions related to the surgical management of patients with anteroinferior glenohumeral instability. Also supported by a PRORP award, the OASIS Trial will prospectively enroll 450 participants with 10% to 20% anterior glenoid bone loss across 15 sites (10 civilian, 5 military) indicated for arthroscopic Bankart repair plus remplissage, open Bankart repair, or the Latarjet procedure to observe treatment outcomes. Given the high prevalence of recurrent glenohumeral instability among servicemembers, 24 this military-civilian collaboration promises to elucidate the limits of arthroscopic stabilization procedures performed in highly active and/or contact athletes, a patient population that has historically been difficult to treat. Additionally, given the expanding nuances of the bipolar bone-loss paradigm,1,14,23 the establishment of a multicenter prospective cohort study is necessary to improve current understandings of the most precise indications for remplissage augmentation of Bankart repairs and likelihood of servicemembers’ return to duty without recurrent instability after glenohumeral stabilization procedures.
Posttraumatic Osteoarthritis: Persistent Challenges and New Approaches
Whether it be in the setting of high-energy periarticular fractures or ACL injuries, the research priorities of multiple subspecialty and multidisciplinary areas converge on PTOA as an area in immediate need of continued innovation. As was the case during the EWI XV Symposium in 2020, 20 the PTOA breakout session provided a forum for clinicians and scientists to confer and generate a knowledge product that clarified the most pressing and conspicuous knowledge gaps and avenues for future study.
Consensus among the participants coalesced around the description of PTOA as a combination of radiographic features (radiographic and/or advanced imaging–based features characteristic of joint degeneration) with joint pain and/or dysfunction. However, the working group acknowledged the lack of an agreed-upon definition of what constitutes “significant clinical symptoms” as well as how exactly these symptoms should be quantified. The MOON Knee Group has gravitated toward a pain score threshold as measured by the Knee injury and Osteoarthritis Outcome Score of <80, but this threshold has been uniquely applied to those patients with a history of ACL reconstruction. 8 The working group further outlined a list of research goals and priorities: (1) short-term assessments of the comparative effectiveness of acute phase interventions, (2) therapies tailored toward specific phenotypes, and (3) clinical trials focused on preventing and/or forestalling disease progression. It was further acknowledged that there is little evidence to support the efficacy of clinical interventions aimed at ameliorating the disease process once tissue damage is fully established, so there remains a pressing need for more work to better understand early detection and risk factor identification, with a special emphasis on those risk factors that may be modifiable and, therefore, are targets for novel interventions. 13
Efforts to assess risk factors for disease onset and progression should focus on the several underlying principal factors: the nature of the precipitating trauma, the resulting alterations of the intra-articular synovial/biologic environment, and the pathomechanical sequalae of residual joint instability. Particularly in the setting of ACL injury, the biological milieu of the acutely injured knee has been implicated in joint inflammation and cartilage breakdown. These alterations continue to be a subject of special interest for researchers.9,22 With the relative safety of acute interventions such as intra-articular corticosteroid injections performed ≤10 days of ACL injury having been recently demonstrated, 3 the working group recognizes the necessity for ongoing research into novel approaches that blunt the inflammatory cascade without diminishing the capacity for healing surgical repairs and ligamentous reconstructions. As previously described, the efficacy of these approaches will require more ambitious and longitudinal clinical trials to determine whether acute interventions are associated with disease progression and/or severity.
Putting It All Together: The Biologic Association Repository and Bioregistry
Orthopaedic-based biologic treatments (ie, orthobiologics) are regulated by the US Food & Drug Administration under the category of human cell and tissue products and offer alternative approaches to manage musculoskeletal disorders. This includes both nonoperative and operative applications, primarily targeting pain relief for symptomatic osteoarthritis (OA)/PTOA, along with the promotion of soft tissue regeneration and repair. 21 However, persistent challenges (such as the lack of standardized procedures for delivery, processing, and characterization), combined with historical deficiencies in reporting requirements, have fueled a longstanding debate over the efficacy of orthobiologic therapies compared with conventional treatment modalities.6,12,17
For more than a decade, consensus groups organized by the AOSSM, the American Academy of Orthopaedic Surgeons, and several athletic associations and committees have been instrumental in establishing consensus statements, reporting standards, and guidelines for orthobiologic treatments.4,5,12,19 In fact, these efforts have led to the adoption of Minimum Information Studies Evaluating for Biologics in Orthopaedics reporting guidelines as well as regulatory recommendations.7,10,16 These resources outline current requirements and considerations necessary for conducting clinical trials, registries, and biorepository-based studies to improve the standardization of orthobiologic therapies for musculoskeletal disorders. Given the importance of standardization and evidence-based practices within the orthobiologic domain of orthopaedics, sports medicine, and pain management, collaborative initiatives that adhere to these guidelines and recommendations have never been more necessary.
The Biologic Association Registry and Biorepository (BARB) is a nationwide, multicenter initiative focused on standardizing and evaluating orthobiologics such as platelet-rich plasma (PRP) to improve consistency in procedures and outcome assessment. The BARB initiative, partnered with the Musculoskeletal Injury Rehabilitation Research for Operational Readiness program at the Uniformed Services University, was established to expand a cohort that encompasses both civilian and noncivilian patient populations (7 civilian sites, 1 military site). This prospective study, incorporating both registry and biorepository components, aims to enroll over 1000 patients with symptomatic tibiofemoral or patellofemoral OA/PTOA. Validated questionnaires are administered ≤12 months (with a 6-month endpoint) after a single or series of intra-articular PRP injection(s). 11 A minimum injection requirement of 3 mL of PRP has been standardized across organizations, and standardized operating procedures have been implemented at each site to ensure consistent collection of details regarding preparation and injection methods as well as product characteristics (such as complete blood count), which will be correlated with patient demographics and outcomes. Excess PRP samples are also stored for proteomic analysis, using previously published targets of interest.25,26
The main objective of this collaborative effort was to integrate clinical data from a diverse patient population and biological factors of PRP that may influence patient responses in the setting of knee OA/PTOA. The insights derived from these findings will then be used to inform machine-learning algorithms designed to predict patient responses to PRP therapy for knee OA/PTOA. Prospective, multicenter efforts between civilian and military investigators will be used to track other joints and conditions and ultimately refine future treatment strategies.
Conclusion
The ongoing partnership between SOMOS and AOSSM in facilitating the Readiness & Sports Medicine section of EWI continues to shape the direction of research focused on improving outcomes associated with the treatment of musculoskeletal DNBI. The most promising avenues for innovation will continue to flow from military civilian collaborations. Resources must be devoted to longitudinal efforts to better characterize the effects of previous treatments and new approaches.
Footnotes
Final revision submitted June 2, 2024; accepted July 2, 2024.
Authors
Ashley Anderson, MD (Walter Reed National Medical Center, Bethesda, Maryland, USA); Aaron E. Barrow, MD (Eglin Air Force Base, Florida, USA); Asheesh Bedi, MD (Endeavor Health, Skokie, Illinois, USA); Travis J. Dekker, MD (United States Air Force Academy, Colorado Springs, Colorado, USA); Michael A. Donohue, MD (United States Military Academy, West Point, New York, USA); Jason L. Dragoo, MD (Department of Orthopedics, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA); James R. Ficke, MD (Johns Hopkins University, Baltimore, Maryland, USA); Michelle M. Gosselin, MD (Naval Medical Center San Diego, California, USA); Joseph R. Hsu, MD (Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA); Christopher Renninger, MD (Walter Reed National Medical Center, Bethesda, Maryland, USA); Andrew J. Sheean, MD (Brooke Army Medical Center, Fort Sam Houston, Texas, USA); Daniel Song, MD (Walter Reed National Medical Center, Bethesda, Maryland, USA); Kurt P. Spindler, MD (Cleveland Clinic, Weston, Florida, USA); Daniel J. Stinner, MD (Vanderbilt University Medical Center, Nashville, Tennessee, USA); Scott Tintle, MD (Walter Reed National Medical Center, Bethesda, Maryland, USA); John M. Tokish, MD (Mayo Clinic Phoenix, Phoenix, Arizona, USA); Robert Waltz, MD (United States Naval Academy, Annapolis, Maryland, USA); Kaitlyn E. Whitney, MPH (Department of Orthopedics, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA); Xiaoning Yuan, MD, PhD (Uniformed Services University, Bethesda, Maryland, USA).
One or more of the authors has declared the following potential conflict of interest or source of funding: A.J.S. has received research support from Arthrex, education payments from Arthrex and Smith & Nephew, and consulting fees from Stryker and has stock/stock options in Springbok Analytics. K.P.S. has received research support from DJO, Medical Device Business Services, and Smith & Nephew; consulting fees from Flexion Therapeutics, the National Football League, and NovoPedics; royalties from Oberd; and honoraria from NovoPedics and is a member of the scientific advisory board for NovoPedics. J.L.D. has received research support from Organogenesis and Terumo; consulting fees from Arthrex, Bioventus, and Organogenesis; nonconsulting fees from Arthrex; and hospitality payments from Zimmer Biomet, DJO, and Stryker. J.M.T. has received research support, consulting fees, and royalties from Arthrex. M.A.D. has received education payments from Arthrex. R.W. has received research support from Arthrex and education payments from Arthrex and Smith & Nephew. A.B. has received consulting fees from Arthrex and royalties from Arthrex and is a member of the advisory board for Springbok Analytics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
Ethical approval was not sought for the present study.
