Renal Function, Appendicular Lean Mass, and Bone Stiffness: Indirect Associations Through Fibroblast Growth Factor 21

Abstract Reduced renal function has been associated with lower skeletal muscle mass and bone stiffness; however, the mechanisms linking renal function to skeletal muscle and bone health remain unclear. Fibroblast growth factor-21, whose circulating levels increase with impaired renal function, may be involved in these associations. This study examined whether renal function indices showed indirect associations with an appendicular lean mass index and bone stiffness through serum fibroblast growth factor-21 levels in middle-aged and older adults. This cross-sectional study included 301 middle-aged and older adults. Estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, serum fibroblast growth factor-21 levels, appendicular lean mass index, and bone stiffness index were measured. Partial correlation, multivariable linear regression, and indirect-effect analyses were performed after adjustment for potential covariates. After adjustment for potential covariates, serum fibroblast growth factor-21 levels were inversely associated with the estimated glomerular filtration rate, appendicular lean mass index, and bone stiffness index and positively associated with the urinary albumin-to-creatinine ratio. In multivariable linear regression analyses, higher serum fibroblast growth factor-21 levels were independently associated with lower appendicular lean mass index and bone stiffness index, whereas neither the estimated glomerular filtration rate nor the urinary albumin-to-creatinine ratio was significantly associated with either outcome. Indirect-effect analyses showed significant indirect associations through serum fibroblast growth factor-21 levels for the associations of the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio with an appendicular lean mass index and for the association of the estimated glomerular filtration rate with the bone stiffness index. The indirect association between the urinary albumin-to-creatinine ratio and the bone stiffness index was not statistically significant. Higher serum fibroblast growth factor-21 levels were independently associated with the lower appendicular lean mass index and bone stiffness index. Cross-sectional indirect-effect analyses suggested indirect associations of the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio with the appendicular lean mass index and of the estimated glomerular filtration rate with the bone stiffness index through serum fibroblast growth factor-21 levels.