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

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.

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.

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).

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.