Table 4

Summary of evidence of risk factors for structural knee OA (semiquantitative synthesis)

Risk factorFollow-up (years)
and
participants (n)
Phase of investigation
(number of studies)
ROBInconsistencyIndirectnessImprecisionPublication biasUpgrading factorsModified GRADEDirection and magnitude*
with structural OA
Age at injury3814 (134)Phase II (1)XUnclearXX++Association of injury age and OA odds is unclear
BMI 2 years post-ACL sx3814 (134)Phase II (1)XUnclearX+++↑ BMI 2 years post ACLRc may ↑ MTF and PFJ OA odds up to 3.5 times
Pre-injury activity level812 (421)Phase II (1)XUnclearXX++Association of pre-injury activity level and OA odds is unclear
Manual occupation3814 (134)Phase II (1)XUnclearXXX+Association of pre-injury occupation and OA odds is unclear
Follow-up length848 (249)Phase I (1)XXUnclearXX+Association of longer time since injury and OA odds is unclear
Injury to sx38 54 75 8910–16 (585)Phase I (2)
Phase II (2)
XXX+Length of time from injury to knee sx may not change OA odds
Bilateral knee injury727 (146)Phase II (1)UnclearUnclearUnclearX+Association of bilateral knee injury and OA odds is unclear
ACL+concomitant injury74 89 11315–37 (504)Phase I (2)
Phase II (1)
X+++ACL+concomitant injury (vs ACL only) ↑ OA odds up to 7.5 times
Second ACL715 (84)Phase I (1)XUnclearUnclearX+Association of second ACL tear and OA odds is unclear
Meniscal injury727 (146)Phase II (1)UnclearUnclearUnclearX+Association of meniscal injury and OA odds is unclear
Bilateral knee sx727 (146)Phase II (1)UnclearUnclearUnclearX+Association of bilateral knee sx and OA odds is unclear
Index knee sx727 (146)Phase II (1)UnclearXX++Association between index knee sx (vs no injury) and OA odds is unclear
ACLnoSx50 85 9812–15 (318)Phase I (2)
Phase II (1)
XXXXX+ACLnoSx (vs ACLR Sx) may not change OA odds
Early ACLRc44 615–37 (266)Phase I (1)
Phase II (1)
XXXX+Early ACLRc (vs delayed or rehab only) may not change OA odds
Delayed ACLRc44 50 61 645–37 (438)Phase I (3)
Phase II (1)
XXXXX+Association of delayed ACLRc (vs early or no sx) and OA odds is unclear
ACL+meniscus sx7432–37 (127)Phase I (1)XUnclearXUnclearX+Association between ACL+meniscal sx (vs ACL only) and OA odds is unclear
ACLRc+meniscal sx (future)8512 (103)Phase II (1)XUnclearX++Association between ACLRc+meniscal sx (future) and OA odds is unclear
ACLRp42 48 50 552–30 (304)Phase I (1)
Phase II (3)
XXUnclearUnclearX+ACLRp (vs ACLRc) may not change OA odds
ACLRc approach4712 (53)Phase II (1)UnclearXXX++Association of ACLRc open (vs closed) and OA odds is unclear
ACLRc graft bundle number35 49 582–5 (624)Phase II (3)XXXX+Double bundle allograft (vs single) may ↓ OA odds by 0.56 times
ACLRc graft type57 81 862–10 (587)Phase I (1)
Phase II (2)
XXXXX+Association of autograft (vs allo) and OA odds are unclear
Sx post-ACLRc6215 (109)Phase I (1)XXUnclearXUnclearXX+Association of sx post-ACLRc and OA odds is unclear
ACLRc revision798 (108)Phase I (1)XXUnclearUnclearXX+Association of ACLRc revision and OA odds is unclear
Meniscal repair2814 (62)Phase I (1)XXUnclearXUnclearX+Association of meniscal repair and OA odds is unclear
Cartilage sx4510 (57)Phase II (1)XUnclearXX++Association of cartilage sx with OA odds is unclear
Anterior tibial motion74 76 78 82 91 947–37 (1193)Phase I (6)XXUnclearXUnclearXX+Association of anterior tibial motion post-ACLRc and OA odds is unclear
Accessory TF motion38 827–14 (197)Phase I (1)
Phase II (1)
XXUnclearUnclearUnclearX+Association of accessory TF motion post-ACLRc and OA odds is unclear
AKP post-ACLRc7720 (142)Phase II (1)UnclearXXX++Association of AKP post-ACLRc with OA risk is unclear
Return to pivoting sport73 78 895–22 (473)Phase I (2)
Phase II (1)
XXXUnclearX+Association of return to pivoting sport with OA odds is unclear
TF ROM post-ACL or ACLRc29 69 74 91 947–37 (1035)Phase I (4)
Phase II (1)
XXX+Association of TF ROM post-ACL or ACLRc with OA odds is unclear
Hop post-ACL or ACLRc59 71 915–37 (425)Phase I (4)XXUnclearXUnclearX+Association of hop function post-ACL or ACLRc and TF OA odds is unclear
Asymmetry of hop function 4 years post-ACL may ↑ PF OA odds 5.1 times
Strength 4 years post-ACL tear7432–37 (127)Phase I (1)XUnclearX+Association of knee extension and flexion strength and OA odds is unclear
SR function post-ACL or ACLRc71 74 895–37 (421)Phase I (2)
Phase II (1)
XXUnclearX+Association of SR knee function post-ACL or ACLRc and OA odds is unclear
SR physical activity 4 years post-ACL7432–37 (127)Phase I (1)XUnclearXUnclearX+Association of physical activity post-ACL or ACLRc and OA odds is unclear
Proximal medial tibial angle7510 (117)Phase I (1)XUnclearXXX+Association of proximal medial tibial angle and OA odds is unclear
Anatomic axis angle7510 (117)Phase I (1)XUnclearXXX+Association of anatomic axis angle and OA odds is unclear
Inflammatory biomarkers6316 (69)Phase II (1)XUnclearXX++Association of assessed biomarkers and OA odds is unclear
  • Bold: Factor(s) with moderate to high quality evidence and OR, or RR consistently positive (more than one analysis) with the largest estimate ≥2.0.

  • *Unclear (estimates significant in inconsistent directions), may (estimates mostly significant in the same direction or mostly not significant), increase or decrease (estimates consistently significant in the same direction).

  • ++, low-certainty evidence; ✓, no limitations; ++++, high-certainty evidence; +, very low-certainty evidence; +++, moderate-certainty evidence; ACL, ACL tear; ACLnoSx, ACL tear with no sx; ACLRc, ACL reconstruction; ACLRp, ACL repair; AKP, anterior knee pain; CKS, Cincinnati Knee Score; GRADE, Grading of Recommendations Assessment, Development and Evaluation; MTF, medial tibiofemoral; n, number; OA, osteoarthritis; PFJ, patellofemoral joint; ROB, risk of bias; SR, self-reported; Sx, surgery; TF, tibiofemoral; x, time; X, serious limitations; XX, very serious limitations.