Risk factors for knee osteoarthritis after traumatic knee injury: a systematic review and meta-analysis of randomised controlled trials and cohort studies for the OPTIKNEE Consensus

Abstract

Objective: To identify and quantify potential risk factors for osteoarthritis (OA) following traumatic knee injury.

Design: Systematic review and meta-analyses that estimated the odds of OA for individual risk factors assessed in more than four studies using random-effects models. Remaining risk factors underwent semiquantitative synthesis. The modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for prognostic factors guided the assessment.

Data sources: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to 2009-2021.

Eligibility: Randomised controlled trials and cohort studies assessing risk factors for symptomatic or structural OA in persons with a traumatic knee injury, mean injury age ≤30 years and minimum 2-year follow-up.

Results: Across 66 included studies, 81 unique potential risk factors were identified. High risk of bias due to attrition or confounding was present in 64% and 49% of studies, respectively. Ten risk factors for structural OA underwent meta-analysis (sex, rehabilitation for anterior cruciate ligament (ACL) tear, ACL reconstruction (ACLR), ACLR age, ACLR body mass index, ACLR graft source, ACLR graft augmentation, ACLR+cartilage injury, ACLR+partial meniscectomy, ACLR+total medial meniscectomy). Very-low certainty evidence suggests increased odds of structural OA related to ACLR+cartilage injury (OR=2.31; 95% CI 1.35 to 3.94), ACLR+partial meniscectomy (OR=1.87; 1.45 to 2.42) and ACLR+total medial meniscectomy (OR=3.14; 2.20 to 4.48). Semiquantitative syntheses identified moderate-certainty evidence that cruciate ligament, collateral ligament, meniscal, chondral, patellar/tibiofemoral dislocation, fracture and multistructure injuries increase the odds of symptomatic OA.

Conclusion: Moderate-certainty evidence suggests that various single and multistructure knee injuries (beyond ACL tears) increase the odds of symptomatic OA. Risk factor heterogeneity, high risk of bias, and inconsistency in risk factors and OA definition make identifying treatment targets for preventing post-traumatic knee OA challenging.

Keywords: anterior cruciate ligament; meniscus; osteoarthritis; risk factor.

Figure 1

PRISMA flowchart. OA, osteoarthritis; PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses; RCT, randomised controlled trial.

Figure 2

Overview of potential risk factors for symptomatic knee OA by follow-up time and knee injury type. To provide an overview of what potential risk factors have been assessed at what timepoints, cohort studies that assessed a risk factor at multiple follow-up points are represented more than once. Apparent redundancies in risk factors are based on differences in definitions use across included studies (eg, terminology used to describe injuries that involved more than one structure). ACL, anterior cruciate ligament; ACLRc, ACL tear reconstruction; ACLRp, ACL tear repair; Ant, anterior; BMI, body mass index; Ext, extension; Flex, flexion; fu, follow-up; Knee injury, inclusive of several injury types; OAT, osteochondral autograft transfer; PF, patellofemoral; ROM, range of motion; RTS, return to sport; TF, tibiofemoral joint; yrs, years. ¹Rehabilitation information provided. ²Intervention no reported. ³Past, present or future. ⁴Present or future. ⁵Serum.

Figure 3

Overview of potential risk factors for structural knee OA by follow-up time and knee injury type. To provide an overview of what potential risk factors have been assessed at what timepoints, cohort studies that assessed a risk factor at multiple follow-up points are represented more than once. ACL, anterior cruciate ligament; ACLRc, ACL tear reconstruction; ACLRp, ACL tear repair; Ant, anterior; BMI, body mass index; Ext, extension; Flex, flexion; Knee injury, inclusive of several injury types; OAT, osteochondral autograft transfer; ROM, range of motion; RTS, return to sport; TF, tibiofemoral joint; yrs (years). ¹Rehabilitation information provided. ²Intervention no reported. ³Past, present or future. ⁴Present or future. ⁵Serum.

Figure 4

Forest plots for risk factor meta-analyses for structural knee OA (stratified by joint compartment). Odds (OR, 95% CI) of structural knee OA by risk factor both stratified by joint compartment (ie, unspecified knee joint compartment, total tibiofemoral joint compartment, medial tibiofemoral joint compartment) and combined across joint compartments. ‘Unspecified joint compartment’ was used when it was not clear which knee joint compartment(s) were assessed. Follow-up is presented in year range. ACLR, anterior cruciate ligament reconstruction; ACL, anterior cruciate ligament; BMI, body mass index; NA, I² could not be calculated based on one study; yrs, years. ¹Reference group is female sex. ²Samples include ACL injured persons only. ³Rehabilitation for ACL tear is stratified by comparison condition (ie, rehabilitation or delayed ACLR) not joint compartment thus estimates represent OA in any knee compartment. Frobell et al, Kvist et al and Neuman et al assessed tibiofemoral and patellofemoral OA with the tibiofemoral estimates included in meta-analyses, Meuffels et al assessed tibiofemoral OA (based on radiographic views reported), Wellsandt et al assessed tibiofemoral OA but only report medial tibiofemoral compartment estimates, while Kessler et al did not specify joint compartment. ⁴Reference is no ACLR. ⁵Odds for every 1 year increase in age. ⁶Odds for everyone one kg/m² increase in BMI. ⁷Reference is semitendinosus tendon autograft. ⁸Reference is ACLR or ACL repair with no graft augmentation. ⁹Reference is no cartilage injury or less severe cartilage injury at ACLR.¹⁰Reference is ACLR with no meniscectomy.¹¹Reference is ACLR with no total medial meniscectomy.