Military populations experience high rates of disability related to post-traumatic osteoarthritis (PTOA), which does not always originate from combat injury. But military researchers are also uniquely positioned to explore therapeutic options to minimize the effect of PTOA.
By Jessica C. Rivera, MD, Joseph C. Wenke, PhD, James R. Ficke, MD, and Anthony E. Johnson, MD
The clinical burden of osteoarthritis affects one in five Americans and results in activity limitations for one in ten.1,2 Osteoarthritis costs more than $128 billion dollars per year in work losses, outpatient physician visits, and surgeries, including total joint arthroplasties.1,3 The World Health Organization has dubbed osteoarthritis the condition with the fourth most impact in terms of disease-free life-years and disability worldwide, while the Centers for Disease Control and Prevention have determined that arthritis is the number-one cause of disability in the US.4
However, those defining the burden of osteoarthritic disease have either focused on degenerative osteoarthritis, which occurs most commonly in adults older than 65 years, or have referenced heterogeneous patient populations. Post-traumatic osteoarthritis (PTOA) represents a different pathology and occurs in a younger population than degenerative osteoarthritis.5 The morbidity of PTOA has not been as clearly defined. One estimate in the civilian trauma literature suggests that PTOA is the cause of 12% of cases of symptomatic arthritis of the hip and knee, costing more than $3 billion per year to treat.6 Ankle PTOA may account for as many as 80% of ankle arthritides.7
The pathology of degenerative osteoarthritis is attributed to a lifetime of wear on the articular cartilage. The cartilage loss is diffuse and involves varying tissue levels throughout the entire joint. For example, unicompartmental knee osteoarthritis may, on radiograph, appear isolated to one compartment; however, mechanical studies indicate that degenerative cartilage is also present in the remaining two compartments, which may even appear grossly morphologically normal.8
PTOA involves a different, though not completely understood, pathophysiology. The traumatic event that violates or disrupts the articular cartilage is focal. Therefore, cartilage cell death begins at a point source while the remainder of the joint, at least initially, may be unaffected.9 If and how focal cartilage injury results in accelerated damage of the remainder of the joint is unknown. Causes of PTOA include intra-articular fractures, ligamentous disruptions and dislocations, meniscal injuries, and chondral fractures.10 Among these diagnoses, the threshold level of energy imparted to the joint required to produce cartilage damage varies (Table 1). Normally, cartilage matrix fluid displaces in response to an applied load, dispersing the load and protecting the subchondral surface.11,12 However, this mechanical property is less effective in the setting of a rapidly applied load, especially when high energy is imparted during the load. Chondrocyte cell damage may be repaired if the cells can maintain their proteoglycan and water content; however, the exact magnitude of load required to make this repair impossible is not known. When this threshold beyond physiological loading is exceeded, however, chondrocytes experience either direct cell death or are damaged enough that proteoglycan replacement is not adequate to restore a normal molecular framework-water ratio. The result is decreased stiffness of the remaining cartilage, which is then prone to further injury through the same cycle of disturbed proteoglycan-water ratio.11
PTOA also occurs following fractures of either the chondral surface alone or subchondral bone. Chondrocytes at the intra-articular fracture edges will die by primary necrosis.9 With gross chondral defects, surrounding chondrocytes will produce matrix molecules at the periphery of the injury but are unable to populate the entire defect.11 There is little to no inflammatory response in isolated chondral fractures. In contrast, fractures that involve the subchondral bone result in bleeding and inflammation, clot formation, presence of mesenchymal stem cells, and the formation of cartilage material. While this “scar” cartilage is not as mechanically sound as uninjured hyaline cartilage, it can restore joint congruity for some time.10,11
The presence or absence of inflammation after joint injury is not the only factor affecting outcome, as different joints exhibit different levels of tolerance for intra-articular injury. Quality of fracture reduction, by minimizing the fracture gap requiring cell repopulation and tissue regeneration, is generally accepted as the critical treatment for intra-articular fractures. However, fracture reduction alone does not seem to account for all predicted outcomes as worse outcomes result after acetabular fractures than tibial plateau fractures when only quality of fracture reduction is considered.13-15 Injuries of the tibial plateau may also be affected by other aberrations such as ligamentous instability, meniscus injury, and malalignment that are not considerations for the hip.16-19 The ankle is a highly constrained joint, but intra-articular injury in the ankle seems to result in higher frequencies of PTOA and poorer outcomes than in the hip and knee.8 It is therefore evident that both joint congruity, mechanical stability, and local cellular factors in light of each individual joint’s physiologic mechanical loads combined portend a joint’s risk of PTOA.
The problem of PTOA in the military
Osteoarthritis causes substantial disability among those serving in the military, including young service members with acute traumatic injury. Rates of osteoarthritis are higher and affected ages are lower in active military service members and veterans than in civilian populations.20,21 Recent conflicts have resulted in a high rate of extremity injuries, as many as 71% of which have been associated with intra-articular injury.22 Osteoarthritis is among the most common causes of disability in service members who are medically retired or separated from the military, and has been so both before and after recent conflicts.23 Comparing cohorts of medically retired individuals prior to and following a decade of combat, rates of knee osteoarthritis as a cause of disability have decreased, while rates of foot and ankle osteoarthritis have increased24 (Figure 1). Proportionally, this is likely due to the shift of medically retired populations who previously experienced degenerative osteoarthritis of the knee compared to later populations who have experienced high rates of extremity injuries resulting in ankle PTOA, such as combat-related distal tibia and hindfoot fractures.
Among our population of service members, a recent publication from our institution aimed to specifically define the burden of PTOA in a cohort of combat-wounded individuals.25 All causes of PTOA resulted in some degree of permanent disability in 126 of 450 soldiers (28%). PTOA was diagnosed either by symptoms or radiographs an average of 19 months following traumatic injury. Although spine injuries were the most common, knee injuries were most likely to result in disabling arthritis (Figure 2). Preinjury conditions could be attributed to the arthritis in only 8% of cases, leaving 94% of appendicular arthritis cases and 75% of axial arthritis cases having a discrete traumatic combat injury as the cause. The most common injury associated with resultant PTOA was intra-articular fracture. In terms of severity of disability, foot and ankle injuries were the most disabling.
One specific area of PTOA research that our institution has focused on is post-traumatic hindfoot and ankle arthritis. Nearly all (91%) of ankle injuries in the aforementioned cohort resulted in an eventual designation of permanent disability due to arthritis.25 End-stage arthritis of the ankle is most often treated by arthrodesis, and in our military population, disability and pain related to injury to the ankle has resulted in late amputations.26 Although we are unable at this time to interrupt the pathogenesis of PTOA following severe lower extremity trauma, we have demonstrated some success in rehabilitation after these injuries, which in turn result in improved functional outcomes despite foot and ankle PTOA. These outcomes are the results of the Return to Run clinical pathway, an integrated orthotic and rehabilitation initiative, and the use of the Intrepid Dynamic Exoskeletal Orthosis (IDEO), a custom carbon-fiber energy-storing ankle foot orthotic fabricated at the Center for the Intrepid, Brooke Army Medical Center, in San Antonio, TX.
Comparative study of the IDEO versus other commonly used off-the-shelf orthoses (i.e., a noncustom carbon-fiber ankle foot orthosis and a posterior leaf spring orthosis) demonstrated in a cohort of 18 limb salvage patients that the IDEO significantly improved tests of agility, power, and speed.27 In a recent publication of 16 combat-wounded individuals who sustained lower extremity fractures resulting in tibiotalar or subtalar PTOA, Patzkowski et al reported that 81% of patients were able to return to running activities, 69% returned to agility sport, and 44% were able to stay on active duty military service; a follow-up publication reported a deployment rate of 19%.28,29 Because the IDEO allows these patients with foot and ankle PTOA to perform higher levels of activity and often reduces pain, greater than 50% of limb salvage patients who received an IDEO who initially desired a late amputation changed their minds.27 Although the IDEO and Return to Run pathway are currently available only at our institution, these results highlight the importance of how a rehabilitation pathway, improved orthotic technologies, and multidisciplinary treatments could improve outcomes for individuals with articular injuries despite PTOA.
Not just a trauma problem
For both deployed and nondeployed service members, noncombat mechanisms remain the most common cause of musculoskeletal injury. Rates of anterior cruciate ligament (ACL) injuries, meniscus injuries, ankle sprains, and shoulder dislocations are higher in active duty service members compared with the general population.30,31 Each of these “sports injuries” also poses a risk for PTOA. Curl et al found that 63% of knees undergoing arthroscopy for other presumed pathology also exhibited a cartilage injury.32 Rates of accelerated osteoarthritis following ACL reconstruction vary widely in the literature and have been reported to be as high as 80% despite evolving techniques including advances in arthroscopy.33-35 Surgical interventions for cartilage repair include microfracture, autologous chondrocyte implantation, and osteochondral autograft transfer, but all result in some impairment affecting an athlete’s return to sport.36 Glenohumeral arthritis is more common in individuals with chronic shoulder instability that requires operative treatment.37 Cartilage damage is common in patients with multiple ankle sprains, and has been identified arthroscopically in 66% to 95% of ankles with lateral ligamentous instability.38,39
PTOA of the knee and hip can lead to early total joint arthroplasty. Current literature is lacking regarding outcomes following total joint arthroplasty performed specifically for PTOA. Arthroplasty for PTOA of the hip poses unique operative challenges not necessarily found in primary cases of osteoarthritis such as post-traumatic deformity and decreased bone stock.40 Fixation of tibial plateau fractures in one study did not preclude early joint replacement in at least 10% of individuals.41 Intra-articular malunion after distal femur or proximal tibia fractures is associated with higher perioperative complications after total knee arthroplasty.42 However, in a recent study of 42 individuals who underwent either hip or knee joint arthroplasty while in the military, 86% were able to continue on active duty service after surgery and 16 individuals were able to deploy.43 While long-term results in this cohort are yet to be seen, arthroplasty remains an option for the young patients whose arthritis, primary or post-traumatic, precludes a desired level of function.
PTOA presents a substantial burden to young people. As evidenced by the study of combat injuries, articular fracture results in PTOA in both the military and civilian trauma literature. However, in the young active military population, the importance of noncombat sports injuries and their contribution to the incidence of PTOA also raises concern.
We propose moving forward with several important research initiatives to minimize the disabling effect of joint damage following traumatic injury:
(1) A greater understanding of the basic science of articular cartilage injury. This includes delineating the processes that cause focal chondrocyte death and how this affects the degenerative risk of the remaining joint.
(2) Identification of patient-related factors that may contribute to poor outcomes following joint injury, such as sex, age, body mass index, smoking, genetic predisposition, and others.
(3) Defining injury-related factors that contribute to PTOA development, such as mechanisms and concomitant joint injuries.
(4) Identification and characterization of treatments that may promote or deter PTOA development (e.g., possible therapeutic and chondrotoxic effects of intra-articular medications, timing and types of surgeries for cartilage repair, joint offloading with bracing modalities, and optimum rehabilitation strategies following operative or nonoperative treatment of joint injury).
(5) Determination of what therapies, including primary surgeries, arthroplasty options, and rehabilitative modalities, will provide the best long-term outcomes for patients with PTOA.
Jessica C. Rivera, MD, recently graduated from orthopedic surgery residency at San Antonio Military Medical Center in Texas, where she is now a primary investigator in the Regenerative Medicine Task Area in the US Army Institute of Surgical Research. Joseph C. Wenke, PhD, is manager of the Regenerative Medicine Task Area, Orthopaedic Trauma Research Program. James R. Ficke, MD, is the upcoming chair of Orthopaedic Surgery at Johns Hopkins University in Baltimore, MD, having previously served as chair of the Department of Orthopaedics and Rehabilitation at San Antonio Military Medical Center and as consultant to the surgeon general for Army Orthopaedics. Anthony E. Johnson, MD, is the upcoming chair of the Department of Orthopaedics and Rehabilitation at San Antonio Military Medical Center.
Disclosure: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the US Department of Defense.
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