Adipokines, which are bioactive substances secreted by adipose tissue, are crucial for immunological control, bone metabolism, and inflammation. Chronic systemic inflammation in rheumatoid arthritis (RA) raises the risk of osteoporotic fractures and speeds up bone loss. A growing body of research indicates that changes in the amounts of adipokines such leptin, adiponectin, resistin, and visfatin may affect the activity of osteoclasts and osteoblasts, which may contribute to skeletal fragility in RA.
Understanding how adipokines interact with bone health is crucial since patients with RA already have an increased risk of fracture due to systemic inflammation, glucocorticoid usage, decreased mobility, and joint degeneration. Examining these correlations may provide information about the processes behind fracture risk and aid in the discovery of biomarkers or treatment targets to enhance bone outcomes in RA. Thus, this study was set to evaluate if circulating adipokines are linked to incidence fractures in RA patients.
The participants in a long-term RA cohort had their banked enrollment blood used to assess three adipokines: adiponectin, leptin, and fibroblast growth factor [FGF]-21. Using median values, adipokine levels were classified as either high or low. Using diagnostic codes and published methods, incident osteoporotic fractures were identified and verified by chart review.
After controlling for age, sex, race, smoking status, body mass index, prednisone usage, disease activity, calendar year, comorbidity score, osteoporosis history, and previous fracture, Cox proportional hazard models assessed adipokines and incident fracture risk.
There were 2527 volunteers in all (mean age of 72 years, 89% male). Over 27,540 person-years of follow-up, 228 incidence fractures occurred (8.3 fractures per 1000 person-years). 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)], with the latter not reaching significance (p=0.13).
Individuals with increased levels of all three adipokines were twice as likely to fracture as those without raised levels [HR: 2.17 (95% CI: 1.27, 3.70) p=0.005]. Overall, independent of other known risk factors such as body mass, smoking, and prednisone usage, elevated adipokines are linked to a higher incidence of fracture in RA patients.
Source:
Baker, J. F., England, B. R., George, M. D., Brubeck, H., Sauer, B., Lenert, A., Roul, P., Thiele, G. M., Mikuls, T. R., & Wysham, K. D. (2025). Adipokines and associations with incident osteoporotic fracture in patients with rheumatoid arthritis. Arthritis Care & Research, acr.25632. https://doi.org/10.1002/acr.25632
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