Knee muscle strength as a mediator of sex differences in incident knee osteoarthritis

Li X, Wu Z, Zhang Y, Zeng C, Lei G, Wei J · Arthritis Research & Therapy

Puts a number on how much of a known risk gap runs through muscle. Eight-year risk of lateral radiographic knee osteoarthritis was 5.9 percent in women and 3.4 percent in men, an odds ratio of 1.72 (95% CI 1.28 to 2.31). Knee extensor strength mediated 33.9 percent of that difference and flexor strength 31.1 percent, with indirect effects of 1.16 (1.05 to 1.27) and 1.14 (1.04 to 1.26); the direct effects not running through strength were 1.46 and 1.48. Incident symptomatic osteoarthritis behaved similarly. The authors read a third of a sex difference travelling through a modifiable variable as an interventional opportunity rather than as an explanation.

Population

Osteoarthritis Initiative participants aged 45 to 79 with no radiographic or symptomatic knee osteoarthritis at baseline: 5,126 knees from 3,056 people for the radiographic analysis and 6,773 from 3,720 for the symptomatic one, followed eight years

Intervention

Exposure: isometric knee extensor and flexor strength at baseline, normalised to body mass index

Comparator

Marginal structural mediation models adjusted for age, race, knee injury history, physical activity, knee alignment, cartilage volume and hormone therapy

Limitations

Observational, so strength may be a marker as much as a cause, and mediation analysis assumes the model is right about which way the arrows point. Strength was measured isometrically and only at baseline, so nothing here tracks a change in strength against a change in risk. Incident radiographic osteoarthritis is a threshold crossing, which misclassifies knees sitting either side of it. The lateral compartment supplied relatively few events, especially in men, and the intervals are correspondingly wide. The cohort is predominantly White. Two-thirds of the sex difference is not explained by strength at all.