Adipokines Predict Incident Osteoporotic Fracture in Rheumatoid Arthritis
A large longitudinal cohort study evaluating the role of adipokines found that higher serum adiponectin and higher leptin were associated with a substantial increase in the risk osteoporotic fractures among individuals with rheumatoid arthritis (RA), the investigators reported in Arthritis Care and Research.
Patients with rheumatoid arthritis (RA) are known to be an increased risk of osteoporosis and fragility fracture due to chronic inflammation, glucocorticoid exposure, and alterations in body composition. This study was designed to determine the role of the adipokines —bioactive proteins derived from adipose tissue—in that risk.
The study included 2512 adults with physician-confirmed RA, predominantly male, and with a mean age of 71 years. At baseline, 648 participants had a history of fracture and 452 reported osteoporosis. During 16,573 person-years of follow-up, 86 incident osteoporotic fractures occurred, yielding an incidence of 0.52 per 100 person-years.
Baseline analyses demonstrated that patients with a prior fracture had significantly higher serum adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) concentrations. Similarly, those with a history of osteoporosis had elevated adiponectin and leptin. After adjusting for demographic, lifestyle, and disease-related factors, higher serum adiponectin was associated with a 43% increase in incident fracture risk (HR, 1.43; 95% CI, 1.07–1.90; P = .01), and higher leptin was associated with a 49% increase (HR, 1.49; 95% CI, 1.11–1.98; P = .006). Importantly, patients with both elevated adiponectin and leptin demonstrated more than a 2-fold increased risk of fracture (HR, 2.14; 95% CI, 1.38–3.33; P = .001).
These findings underscore the potential role of adipokines as biomarkers for bone fragility in RA. The combined elevation of adiponectin and leptin appears to identify a subgroup of patients at particularly high risk, independent of traditional risk factors such as age, sex, BMI, glucocorticoid use, or baseline disease activity.
The study suggests that measurement of circulating adipokines may complement existing fracture risk assessment strategies in RA. Longitudinal studies are needed to determine whether changes in adipokine levels over time provide additional predictive value and whether targeting adipose tissue–derived pathways could represent a novel strategy for fracture prevention in this population, the authors stated.
Reference:
Baker JF, England BR, George MD, et al. Adipokines and Associations With Incident Osteoporotic Fracture in Patients With Rheumatoid Arthritis. Arthritis Care Res. Published online August 18, 2025. doi:10.1002/acr.25632
