Association of leptin levels with radiographic hand osteoarthritis and severity among a cohort of midlife women

Purpose: Associations of leptin levels with knee osteoarthritis (OA) risk have suggested a metabolic role of obesity in addition to the impact of mechanical loading in the etiology of OA. The few studies examining an association of leptin and OA of the hand, a non-weight bearing joint, have been null but were limited by small sample sizes or the use of photography for hand OA assessment. The purpose of this study was to relate serum leptin levels to radiographically-defined hand OA and severity in a large, well-characterized population of midlife women. Methods: Participants at the Michigan site of the Study of Women’s Health Across the Nation (SWAN) underwent hand radiographs and each joint within the hand was scored for OA using the Kellgren/Lawrence (KL) classification. Leptin was assayed in serum collected at the same time the radiographs were acquired. Results: Among the 543 Michigan SWAN women with a hand x-ray, the average age of participants was 46.1 years of age, the average body mass index (BMI) was 32.1 kg/m2 and 60% of participants were African-American and 40% were white. One-quarter (n=139) of participants had radiographic hand OA, defined as at least one hand joint with a KL score≥2. In multivariable models adjusting for age, race/ethnicity and BMI, there was no statistically significant association between serum leptin and this global definition of hand OA. However, when considering the OA status of each joint individually and adjusting for the inter-individual clustering of joints, there was a statistically significant association of serum leptin and hand joint OA. A 5 ng/mL higher serum leptin level was associated with 6% higher odds of a joint having radiographic OA (odds ratio=1.06, 95% confidence interval 1.01, 1.12) after adjusting for age, race/ethnicity and BMI. Similarly, the total hand OA burden, defined as the summed value of the KL scores for all joints on a given hand was positively associated with serum leptin levels. A 5 ng/mL higher serum leptin level was associated with a 1.04 higher total OA burden score. Conclusions: Our findings support a metabolic role of obesity in hand OA given observed associations of serum leptin with hand joint OA and hand OA severity. Consideration of the multiple mechanisms by which excess adipose tissue may be detrimental for joint damage is needed to effectively understand the disease and work towards prevention and treatment.