Discussion
The most important finding in this review was that there is an increased risk of ACL injury in individuals with GJH. This is similar to a previous meta-analysis assessing the influence of GJH on knee injuries in general,3 although, since the publication of that particular meta-analysis, additional studies have reported conflicting results.26 45 The increased risk of primary ACL injury in individuals with GJH found in this review could not be established when analysing female individuals separately. In females, the results were more ambiguous. This is surprising, since female sex16 46 and GJH are regarded as important risk factors for ACL injury and hypermobility is more common in females.11 Because of this, we hypothesised that part of the reason for the increased risk of ACL injury, seen in females, could be attributed to hypermobility. However, in females, other possible risk factors, such as reduced neuromuscular control,47–50 a narrow femoral notch4 51 or hormonal factors, could be of greater significance.52
Postoperative outcomes
The results showing increased postoperative laxity, with no difference at 2 years but an increase in the group with GJH at 5 and 8 years, are interesting. It appears that the GJH has a greater impact on postoperative knee laxity after 2 years have passed, beyond the immediate rehabilitation phase. Possibly, repetitive strain on the ACL graft has a different effect on the collagen tissue in the graft in patients with GJH. GJH is related to alterations and impairment of the extracellular matrix, primarily collagen, elastin and fibrillin.53 Interestingly, one study has demonstrated that biological failures were associated with GJH.33 Biological failures were, by the authors, defined as faliures where no technical cause could be identified and where no traumatic injury had occurred. In 74% of the cases in the group with biological failures, the patients’ grafts were intact but lax (non-functional according to the authors). Thus, increasing joint hypermobility may be associated with increased risk of biological failure, as defined above, with the difference becoming more obvious after the first 2 years after ACL reconstruction.
There was considerable agreement between studies showing that GJH has a negative influence on postoperative patient-reported outcome in patients with previous ACL reconstruction. Using patient-reported outcome measurements is important in order to quantify patient satisfaction. The subgroup of patients with GJH are already at a disadvantage preinjury, as is illustrated by a recent study of 1006 non-injured Danish adults demonstrating that patients with GJH or knee joint hypermobility had a twofold probability of reporting symptoms such as knee pain, inferior performance of usual activity and reduced health-related quality of life.15 It is therefore especially important to optimise both surgical interventions and rehabilitation in this group of patients.
In this systematic review, OA was evaluated in two studies with ACL-injured patients showing no difference in OA at short-term to mid-term follow-ups with respect to the presence of GJH. Previous studies have assessed the association between OA and GJH in the general population with inconclusive results.54–56 It has been suggested that cross-sectional investigations of both OA and GJH at older ages may be difficult to interpret, as hypermobility might be a marker of fitness, associated with less OA.55 More studies, with longer follow-ups beyond 10 years, are needed to draw definite conclusions. In line with the argument above, it is recommended to assess GJH in these patients preoperatively, with a subsequent long-term follow-up to avoid misinterpretation of the results.
Should the presence of GJH influence graft choice?
The choice of graft might be particularly important in patients with GJH. This review reported that patients receiving HT autografts had increased instrumented anteroposterior laxity and inferior Lysholm and IKDC scores compared with patients receiving PT autografts. In the general population, previous systematic reviews have reported that PT autografts produce less anteroposterior laxity but with poorer results regarding postoperative complications, including anterior knee pain and kneeling pain, compared with HT autografts.57–59 In terms of laxity, the same results were found in this review for the subset of patients with GJH. However, in contrast to the general ACL-reconstructed population,60 patients with GJH receiving the PT autograft also benefited from superior subjective outcomes, according to the results of the present review. With the knowledge available at present, a PT autograft appears to be the better alternative compared with HT autografts in patients with GJH.
Limitations and strengths
A few limitations relate to the overall quality of the studies included in this review. First, several methods were used to assess GJH using different cut-offs for the definition of hypermobility. Consequently, no general recommendations could be given in terms of aspects of treatment related to a specific degree of hypermobility; only general statements can be made.
Second, the lack of an a priori sample-size calculation of the involved studies raises concerns about a type-II error possibly being present in several of the studies in this review.
Third, the heterogeneity of the assessment methods for definition of GJH and the multiple confounding variables limits the ability to pool data for a quantitative analysis. This review focused in particular on the confounders sex and age, as female sex and younger age are risk factors for primary ACL injury and ACL revision16 61 and GJH is more common at younger ages and in females.11 However, there are many other important potential confounders, such as extrinsic and intrinsic risk factors and injury mechanisms, that were not acknowledged in the majority of the studies. One of the studies in this review conducted both multivariable adjusted and unadjusted analyses. When the authors adjusted for known confounders, this changed the regression coefficients by at least 10%, emphasising the importance of considering potential confounders in analyses of risk factors for ACL injury.62
Last, one first author (Dr Sung-Jae Kim) contributed with five of the studies (22%) eligible for this review. His research group provided the majority of or all the available evidence on the following aspects of this review: radiography, postoperative knee laxity, postoperative clinical outcome and the effect of graft type in patients with GJH. This limits the generalisability of our conclusions since joint hypermobility varies among ethnic groups11 and there is an ongoing debate concerning the possible association between ACL injury and genetic variations/polymorphisms.63
Considering a lack of studies and the limitations listed above, there was insufficient evidence to draw any definitive conclusions at present for the following analyses; bilateral ACL injuries, graft failure and return to physical activity.
Particular strong points include the homogeneous primary end-point, ACL injury, in contrast to more vaguely defined knee injury assessed in a previous systematic review.3 Moreover, this review includes primary ACL injury risk, graft-failure risk and postoperative outcome, giving a comprehensive overview of the scientific evidence relating to the association between the ACL-injured athlete and GJH.
Future perspectives
With respect to future studies, there are some aspects that could improve the quality and between-study comparisons in the future. Several methods with different cut-offs were used to establish the diagnosis of GJH. It is important to standardise the definition of GJH across all subspecialised fields in order to create comparable data. The recommendation is to use the definition of GJH presented in the consensus document by Malfait et al in 2017, presenting cut-offs as follows: ≥6 for pre-pubertal children and adolescents, ≥5 for pubertal males and females up to the age of 50, and ≥4 for those >50 years of age.8 In the ACL-injured individual, the use of the 5-point questionnaire8 10 or an injury allowance point64 is recommended to mitigate the bias of the disturbed range of motion of the ACL-injured knee. Moreover, the use of grafts should be meticulously considered in patients with GJH. Future randomised controlled studies are needed to draw definite conclusions regarding the preferred use of grafts and the use of surgical techniques in these patients. On current evidence, we recommend the use of PT autografts.