Frontiers in Medicine · Oct 9, 2026

Association of Serum GDF-15 with Bone and Muscle Parameters in Community-Dwelling Individuals

By Profili NI, Makrogiannis S, Castelli R et al.

INTRODUCTION: Muscle mass and bone mineral density decrease with aging, although following different patterns among males and females. Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine and has emerged as a key biomarker for inflammation, tissue injury, and metabolic stress. We tested the association between GDF-15 and specific bone and muscle parameters in a large cohort of community-dwelling subjects. METHODS: The SardiNIA survey included 4,842 subjects (2,795 females). All underwent a detailed medical visit and laboratory testing. Peripheral quantitative computed tomography at the tibia was performed to evaluate volumetric bone mineral density and bone microstructure as well as muscle mass. RESULTS: Multivariate regression analysis showed that GDF-15 was negatively associated with cortical bone density (Beta -0.042, p < 0.001) in females. In males, total bone density and trabecular bone density at 4% site and cortical bone area at 38% site were negatively associated with GDF-15 levels (respectively, Beta -0.016, p = 0.027, Beta -0.014, p = 0.039, and Beta -0.022, p = 0.002). Multivariate regression analysis for muscle parameters showed that GDF-15 was negatively associated with muscle density (Beta -0.002 in females and males, p < 0.001 for all) and muscle area (Beta -0.338, p = 0.003, Beta -0.744, p < 0.001). CONCLUSIONS: Higher circulating GDF-15 levels were independently associated with lower volumetricBMD and poorer muscle parameters in both women and men. These findings support the potential role of GDF-15 as a biomarker of age-related musculoskeletal decline, although longitudinal studies are needed to determine whether GDF-15 contributes to the development of these changes or simply reflects the underlying biological processes.

doi.org/10.3389/fmed.2026.1920342Open accessPubMed 42920449Biomarkers