Association between fibroblast growth factor 21 and bone mineral density in adults

Purpose: Animal-based studies have reported a decrease in bone mass resulting from high level of fibroblast growth factor 21 (FGF21). However, the correlation between plasma FGF21 levels and bone mineral density (BMD) is paradoxical in previous human-based studies, and the associations between FGF21 gene polymorphisms and BMD haven’t been reported yet. Therefore, here, we evaluated plasma FGF21 levels with sufficient study samples, and performed genetic association test to reveal the physiological and genetic role of FGF21 on BMD in adults. Methods: Plasma and genetic samples containing 168 and 569 Han Chinese subjects, respectively, were employed in this study. Fasting plasma FGF21 levels were determined using enzyme-linked immunosorbent assay (ELISA). Regional BMD values were measured by dual energy X-ray absorptiometry (DXA). Five variants of FGF21 gene were successfully genotyped. Results: Physiological association suggested that plasma FGF21 levels were inversely correlated with BMD in femoral neck (Neck-BMD: P = 0.039) and Ward’s triangle (Ward’s-BMD: P = 0.002) of hip region. A FGF21 gene variant, rs490942, was significantly associated with the increase of Ward’s-BMD in total (P = 0.027) and female (P = 0.016) cohorts, as well as Neck-BMD in female cohort (P = 7.45 × 10⁻³). Meanwhile, eQTL results indicated that this SNP was related to the decreased level of FGF21 gene expression. Conclusions: Taking together from both physiological and genetic levels, we suggest that FGF21 is inversely associated with regional BMD. And we haven’t observed sex-specific effect in this study.