Familial Predisposition to Anterior Cruciate Ligament Injury: A Systematic Review with Meta-analysis

Abstract

Background: Having a family history of anterior cruciate ligament (ACL) injury has been investigated in the literature but few studies have focused on this factor specifically or reported their outcomes by sex.

Objective: We aimed to systematically review family history as a risk factor for sustaining a primary ACL injury and the impact it has on ACL graft rupture or contralateral ACL injury in male and female individuals.

Methods: A literature search was completed in seven databases from inception until March 2021 to investigate primary and subsequent ACL injuries in those with a family history of ACL injury. Articles were screened by prespecified inclusion criteria, and the methodological quality of each study was determined. Study results were combined using an odds ratio (OR) meta-analysis. Subgroup analysis was also completed by sex for primary ACL injury, as well as by graft rupture and contralateral ACL injury for subsequent ACL injuries.

Results: Twelve studies were acquired for systematic review and meta-analysis. Four studies that investigated primary ACL injury, seven that investigated ACL graft and/or contralateral ACL ruptures and one study that investigated both primary and subsequent ACL injury. Having a family history of ACL injury increased the odds of injury across all outcomes. Those with a family history had a 2.5 times greater odds for sustaining a primary ACL injury (OR 2.53 [95% confidence interval [CI] 1.96-3.28, p < 0.001)]. There was no significant difference of injury odds for primary ACL injury when analysed by sex. Family history of ACL injury was found to increase the odds of subsequent ACL injury by 2.38 (95% CI 1.64-3.46, p < 0.001) and was significant for both graft ruptures (OR 1.80 [95% CI 1.20-2.71, p = 0.005]) and contralateral ACL injuries (OR 2.28 [95% CI 1.28-4.04, p = 0.005]). When compared directly, the odds of sustaining a graft rupture versus a contralateral ACL injury were similar for those with a family history. Outcomes were not frequently reported by sex for subsequent ACL injuries.

Conclusions: Having a family history of ACL injury more than doubles the odds of sustaining a primary or subsequent ACL injury. However, if a family history of ACL injury is present, the sex of the athlete does not increase the risk for primary injury nor is there a difference in the risk for a subsequent graft rupture compared to a contralateral ACL injury.

Clinical trial registration: PROSPERO: CRD42020186472.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of the search strategy

Fig. 2

Odds of sustaining a primary anterior cruciate ligament injury with a family history of anterior cruciate ligament injury. The Hägglund and Waldén [27] study includes a female individual-only population. For Flynn et al. [8], only the results from first-degree relatives were used in the meta-analysis. CI confidence interval, M–H Mantel–Haenszel

Fig. 3

Odds of sustaining a primary anterior cruciate ligament injury in female individuals with a family history compared to those without. CI confidence interval, M–H Mantel–Haenszel

Fig. 4

Odds of sustaining a primary anterior cruciate ligament injury in male individuals with a family history compared to those without. CI confidence interval, M–H Mantel–Haenszel

Fig. 5

Odds of sustaining a primary anterior cruciate ligament injury in male individuals compared to female individuals in those with a family history. An odds ratio > 1 indicates increased odds for anterior cruciate ligament injury in male individuals. CI confidence interval, M–H Mantel–Haenszel

Fig. 6

Odds of sustaining a subsequent anterior cruciate ligament injury (anterior cruciate ligament graft rupture or contralateral anterior cruciate ligament injury) in those with a family history compared to those without. Note that for Bourke et al. [19] and Morgan et al. [26], follow-up data at 5 years were used in the meta-analysis. CI confidence interval, M–H Mantel–Haenszel

Fig. 7

Odds of sustaining an anterior cruciate ligament graft rupture in those with a family history compared to those without. CI confidence interval, M–H Mantel–Haenszel

Fig. 8

Odds of sustaining a contralateral anterior cruciate ligament injury in those with a family history compared to those without. CI confidence interval, M–H Mantel–Haenszel

Fig. 9

Odds of sustaining an anterior cruciate ligament (ACL) graft rupture compared to a contralateral ACL (CACL) injury in those with a family history. CI confidence interval, M–H Mantel–Haenszel