High FGF21 levels are associated with altered bone homeostasis in HIV-1-infected patients

Fibroblast growth factor-21 (FGF21) has emerged as an important regulator of glucose, lipid, and body weight homeostasis. However, recent experimental studies have reported that increased FGF21 levels may lead to bone loss.

To assess the relationship of serum FGF21 levels and altered bone homeostasis in HIV-1-infected patients.

Cross-sectional study of 137 HIV-1-infected patients and 35 healthy controls conducted at the Hospital de la Santa Creu i Sant Pau, Barcelona. Among HIV-1-infected patients, 35 were untreated (naïve), 43 were treated with antiretrovirals (HIV-1/ART) with no lipodystrophy, and 59 patients were HIV-1/ART and experienced lipodystrophy. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy X-ray absorptiometry. Serum levels of FGF21, receptor activator of nuclear factor (NF)-KB ligand (RANKL), and C-telopeptide of type-I collagen (CTX-1) were measured by enzyme-linked immunosorbent assays. Serum levels of osteocalcin, osteoprotegerin, leptin, tumor necrosis factor-α, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 were determined using an antibody-linked, fluorescently labeled microsphere bead-based multiplex analysis system.

Alterations in bone parameters and bone homeostasis marker levels were consistent with higher turnover and bone loss in HIV-1 infected patients. FGF21 correlated negatively with BMD and BMC. FGF21 correlated positively with serum levels of osteoprotegerin and CTX-1, as well as with the CTX-1/osteocalcin ratio.

Elevated FGF21 levels are associated with poor bone homeostasis in HIV-1-infected patients. Increases in FGF21 serum level may be an indicator not only of metabolic derangement but it may also serve as a biomarker of altered bone homeostasis in HIV-1 infected patients.