Osteoarthritis (OA) is a leading cause of disability; the escalating prevalence of this condition is largely driven by the aging of the population and the rise in obesity¹. Factors that alter joint biomechanics, such as injury, may accelerate progression to OA. The knee is one of the most commonly injured joints in the body. Anterior cruciate ligament (ACL) injury, meniscal tear, and direct injury to the articular cartilage are all associated with knee OA². The risk of OA 10 or more years following knee injury has been estimated to be 13% among individuals with isolated ACL injuries and 21–48% among those with both ACL and meniscal injuries³. Knee injury may initiate or accelerate changes in joint metabolism that lead to the degeneration of cartilage and the formation of osteophytes^4–9.

Joints that are hypermobile present with a range of motion that is considered greater than normal, and this excessive motion and associated laxity of joint tissues could increase a joint’s vulnerability to injury and may lead to degenerative changes in joint tissues over time. Current evidence suggests that joint hypermobility is a risk factor for both knee joint injury¹⁰ and knee OA^11–13. For the knee, both generalized joint hypermobility (hypermobility at more than one joint) and knee-specific hypermobility have been linked to knee injury in young athletes^14,15, but associations between joint hypermobility and injury in non-athletes or in adults have not been reported. The combination of joint hypermobility and knee injury, which both may aberrantly alter joint tissues, could plausibly amplify the susceptibility to knee OA, although no prior large cohort study has examined the interaction of joint hypermobility and injury in relation to OA.

The purpose of this study was to evaluate whether joint hypermobility modifies the association of knee joint injury and knee OA among adults from three large studies that included participants with and without OA and comprised identical ascertainment of the exposure, outcomes, and covariates. Our hypothesis was that the occurrence of knee OA would be magnified for participants with a history of knee injury and with vs without joint hypermobility.

Within the GOGO, GO, and JoCoOA studies, there were respectively 2,341, 1,872, and 1,987 total participants included for analysis (Figure 1). Demographic and clinical characteristics of study participants are presented in Table 1. Mean age across the three studies was similar, though participants in GO were slightly older. Each study consisted primarily of women, with the highest proportion observed in the GOGO cohort (78%). JoCoOA was the only study that recruited African-American participants (34%). Compared with GO and GOGO, JoCoOA participants had a greater mean BMI (28, 29, and 31 kg/m², respectively).

Of the three OA variables, evidence of knee pain was more frequent than evidence of either knee rOA or knee sxOA in each of the three study cohorts. A majority of GOGO participants reported knee pain (66%), which was more common than in JoCoOA (45%) or GO (33%) participants. The proportion of participants with radiographic evidence of knee OA was similar between GOGO and JoCoOA (42% and 39%, respectively), though greater than the proportion of participants with rOA in GO (32%). Fewer than one-third of participants across the three cohorts had knee sxOA. Regarding joint hypermobility, a Beighton score ≥ 4 was relatively uncommon, but was recorded most frequently in the GO study (11%), followed by JoCoOA (7%), then GOGO (3%). Prior knee injury was reported in 16% of JoCoOA participants, a greater proportion than the 10% and 11% of GO and GOGO participants, respectively.

Knee pain, knee rOA, and knee sxOA were consistently and strongly associated with knee injury in all three studies. Joint hypermobility modified this association in some but not all of our studies. In particular, joint hypermobility amplified the association of knee injury with knee rOA and sxOA in the GOGO study. Overall, differences in the knee injury-OA association by hypermobility status were not statistically significant in GO and JoCoOA.

The association of knee injury and knee OA from this study are consistent with the broader literature and in particular, larger population-based studies^25–31. Joint hypermobility has been shown to contribute to a higher incidence of musculoskeletal injury³², and it may be associated with more severe injuries that could ultimately lead to OA. For example, time to return to play and period of disability have been noted to be longer in professional soccer players with than without joint hypermobility³³. Results for GOGO support a potential linkage of knee injury and joint hypermobility which is associated with knee OA, although this connection was not observed in the other two studies.

Differences in the results by study may be due to differences in how participants were recruited. Because GOGO participants were recruited from families with at least one sibling pair with hand OA, findings of magnified associations of knee injury and knee OA among those with joint hypermobility may be unique to that population. Further, the results from GO may also be unique, given that specific criteria were imposed for enrollment into the case and control arms of this cohort. JoCoOA is the only one of these three studies that is community-based in which both White and African American individuals were enrolled without regard to OA status, and thus, this cohort may be more representative of a general population than the other two studies. Further, results from a sensitivity analysis restricting the JoCoOA cohort to White participants were similar to those observed for the full study, but with stronger associations overall. Accordingly, the JoCoOA results may provide the best indication of the role joint hypermobility has as a modifier of the association of knee injury and knee OA in the general population.

Considering the imprecision of the estimates across all three studies, which was largely driven by the low frequency of joint hypermobility, caution is warranted in the interpretation of these differences. Most likely, results from JoCoOA suggest that the presence of joint hypermobility in middle-aged to older adults may not have much of an influence on the knee injury-OA association. Since knee injury is strongly associated with knee OA, the additional presence of general joint hypermobility may not provide a notably increased risk for OA.

An important strength of the current analysis is that all three data sources have identical measures of knee injury, OA, pain, joint hypermobility, and covariates, which allowed for a descriptive comparison of results of the knee injury-OA association. Further, JoCoOA provided community-based estimates that may be more generalizable to an adult population than the other two studies. However, a limitation is that misclassification of injury and joint hypermobility is possible. An individual’s recall of injury may not be reliable, including the timing of the injury. Participants in these studies who had joint hypermobility in youth could be classified as “not hypermobile” at the time of study assessment if they experienced joint stiffening with age or following an injury. The present analyses were cross-sectional, which limits our understanding of the sequence of events in the joint hypermobility, injury, and OA relationships. Differences in sampling (recruiting specifically based on presence or absence of OA [GO, GOGO] vs. population-based [JoCoOA]) and designs (cohort and case-control) across the studies may partly explain variation in study results.

In summary, the presence of joint hypermobility may not intensify the already robust association between knee injury and knee OA in a general population of adults. Longitudinal studies may clarify whether joint hypermobility is an initial factor that contributes to an increased risk of injury, and in turn, an increased risk for posttraumatic OA.