Adipokines and Associations with Incident Osteoporotic Fracture in Patients with Rheumatoid Arthritis.

Purpose: We assessed whether circulating adipokines are associated with incident fractures in patients with rheumatoid arthritis (RA).

Methods: Three adipokines (adiponectin, leptin, fibroblast growth factor [FGF]-21) were measured using banked enrollment serum from participants in a longitudinal RA cohort. Adipokine levels were dichotomized as high/low using median values. Incident osteoporotic fracture was defined based on published algorithms using diagnostic codes and confirmed by chart review. Cox proportional hazard models evaluated adipokines and incident fracture risk adjusting for age, sex, race, smoking status, body mass index, prednisone use, disease activity, comorbidity score, calendar year, osteoporosis history, and prior fracture.

Results: A total of 2527 participants were included (89% male, mean age 72 years). There were 228 incident fractures over 27,540 person-years of follow-up (8.3 fractures per 1000 person-years). After adjustment, the risk of incident fracture was increased for high levels of leptin [HR: 1.47 (95% CI: 1.15, 1.90) p=0.003], FGF-21 [HR: 1.39 (95% CI: 1.16, 1.67) p<0.001], and adiponectin [HR: 1.21 (95% CI: 0.94, 1.55)], the latter not achieving significance (p=0.13). Participants who had elevated levels of all three adipokines experienced twice the risk of fracture compared to those in whom none was elevated [HR: 2.17 (95% CI: 1.27, 3.70) p=0.005].

Conclusions: Elevations in adipokines are associated with an increased risk of fracture in patients with RA, independent of other established risk factors including body mass, smoking, and prednisone use. This supports further investigation understanding whether this association is related to altered body composition or disrupted metabolic pathways.