The data add to the growing body of evidence that women, but not men, with thigh muscle weakness are at an increased risk of RKOA and suggest that targeting specific impairments in muscle activation to increase strength per anatomical cross-sectional area may be important in women at risk of knee OA, wrote Adam G. Culvenor, PhD, of Paracelsus Medical University in Salzburg, Austria, and colleagues in Arthritis Care & Research.

The OAI is an ongoing multicenter longitudinal study of 4,796 subjects ages 45 to 79. The current analysis focused on RKOA incidence. A total of 161 knees from participants who demonstrated incident RKOA over 48 months of follow-up were included. Patients underwent baseline magnetic resonance imaging (MRI) acquisition of the thigh and maximal strength measures of the knee extensors and flexors. Patients were matched by baseline Kellgren-Lawrence grade (0/1) to 186 controls without RKOA who also had baseline thigh MRI and thigh strength measures.

A total of 100 of the cases knees (62%) and 108 of the control knees (58%) were from females. At baseline, the patients’ mean ages were 61 for the participants and 60 for the controls. The frequency of baseline Kellgren-Lawrence grade 1 was 71% in the cases and 72% in the controls. BMI was higher in the cases compared with the controls for both men (29.4 versus 27.8, P=0.015) and women (28.9 versus 27.0, P=0.001).

Women with incident RKOA had 5.2% greater knee extensor anatomical cross-sectional areas (ACSAs) and 7.1% lower knee strength compared with the control knees. These differences resulted in unadjusted increased odds of incident RKOA of 1.47 (95% CI 1.10-1.96, P=0.009) for knee extensor-specific strength and 1.41 (95% CI 1.06-1.89, P=0.017) for knee flexor-specific strength. In men, knee extensor ACSAs and strength were similar between the case and control knees.

In analyses adjusting for BMI and age, low knee extensor-specific strength showed a nonsignificant trend towards an increase in incident RKOA in women (OR 1.33, 95% CI 0.99-1.82, P=0.06). The association between knee extensor-specific strength and incident RKOA remained nonsignificant in men when adjusting for BMI and age (P=0.446).

Similarly, knee flexor-specific strength lost significance as a predictor of RKOA in women after adjustment (P=0.113), while knee flexor ACSAs remained unrelated to incident RKOA in both women and men.

In women, a greater BMI was weakly but significantly associated with lower muscle-specific strength (r=-0.29, P<0.001), while knee extensor-specific strength in men was not significantly associated with BMI (r=0.01, P=0.962). A similar pattern was observed in the relationship between knee-flexor characteristics and BMI.

Men with greater BMI have more contractile tissue (and strength), while women with greater BMI apparently have more non-contractile (adipose) tissue, Culvenor and colleagues explained. “The lower muscle-specific strength in the presence of higher BMI in women (possibly driven by greater intramuscular adiposity), but not in men, may provide a possible explanation for the divergent risk of incident RKOA and other RKOA outcomes in men and women with muscle-strength deficits, and in the mechanism by which BMI increases the risk of incident RKOA in men and women.”

The investigators said that the results contrast with other muscle-specific strength data from the MOST cohort, which had 1,303 participants and showed no statistically significant relationship between knee extensor-specific strength and incident RKOA. “However, in that previous study whole thigh muscle mass measured by dual energy x-ray absorptiometry was used rather than quadriceps ACSA, suggesting that specific strength determined by MRI may be more sensitive in detecting the relationship with incident RKOA.”

Regarding study limitations, the authors cited the lack of an exact voluntary muscle-activation measure in the OAI and lack of assessment of intramuscular fat. In addition, although the study included ≥100 incident RKOA female cases and controls, the trend for significant differences in muscle-specific strength when adjusted for BMI suggests that the analysis may have been underpowered.

• Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner