Knee Osteoarthritis: Intersections of Obesity, Inflammation, and Metabolic Dysfunction.

Abstract

Background: Obesity is a risk factor for osteoarthritis (OA) and may impart joint-damaging effects through dysfunctional metabolic mechanisms associated with increased adipose tissue.

Objective: To evaluate the relationship between cardiometabolic markers and measures of knee OA from radiographs and magnetic resonance imaging (MRI).

Methods: Data from 1,066 National Health and Nutrition Examination Survey (NHANES) III participants (60+ years of age) was used to examine relationships of radiographic knee OA and cardiometabolic measures. Data from Michigan Study of Women’s Health Across the Nation (SWAN) participants was used to relate serum leptin levels with prevalent and incident knee OA and to MRI-defined measures of knee joint damage. Results: The prevalence of knee OA in the NHANES III sample was 34% (average age 70.5 years). The baseline prevalence in Michigan SWAN (average age 46 years) was 18%; at follow-up visit 11, when participants were average age 57 years, the prevalence was 65%. Cardiometabolic biomarkers were associated with knee OA in both populations, independent of body size. Among NHANES III participants, those with knee OA had 35% higher HOMA-IR measures and 52% higher serum leptin levels compared to those without knee OA. The magnitude of the association between HOMA-IR and knee OA was strongest among men whereas leptin was more strongly associated among women. Serum leptin levels were associated with prevalent and incident knee OA in Michigan SWAN. Effect estimates were similar in the two populations; a 5 ng/mL increase in serum leptin was associated with 28% higher odds of knee OA among obese NHANES III women and with 38% higher odds among Michigan SWAN women. In SWAN, serum leptin levels 10 years prior to MRI assessment were associated with more severe cartilage defects, larger bone marrow lesions and osteophytes, meniscal tears, synovitis and joint effusion.

Conclusions: Cardiometabolic dysfunction is associated with knee OA and increased serum leptin levels are associated with prevalent and incident knee OA and MRI-defined knee joint damage among women. These findings support a metabolic role of obesity in knee OA. Management of cardiometabolic dysfunction among obese individuals may be beneficial in forestalling the onset or progression of knee osteoarthritis.