Follicle‐stimulating hormone (FSH), interleukin‐1 (IL‐1) and bone density in adult women

Abstract

This study tested the hypothesis that FSH promotes bone loss by inducing secretion of bone‐resorbing cytokines or by altering their receptor expression. Thirty six women (20–50 years old) were assessed for bone mineral density (BMD), circulating FSH, cytokine and soluble receptor concentrations, and expression of cytokine receptors on monocytes. Isolated mononuclear cells were also incubated in vitro with FSH. The results indicated that BMD was inversely related to serum FSH (R: −0.36 to −0.52, P: 0.03 to 0.001, depending upon skeletal site), and also related to physical activity and body composition. FSH induced mononuclear cells to secrete IL‐1β in proportion to the expression of FSH receptors on the monocytes, and serum FSH correlated with plasma IL‐1β. The ratio of plasma IL‐1β to IL‐1 receptor antagonist (IL‐1Ra) was inversely related to BMD (R = −0.53, P = 0.002) in all but the most physically‐active women, who had lower IL‐1 type I receptor expression relative to type II (decoy receptors, P = 0.01). Physical activity correlated with soluble IL‐1 receptor secretion (R = 0.53, P = 0.003) and IL‐1Ra correlated with % body fat (R = 0.66, P < 0.0001). In conclusion, BMD is related to serum FSH, physical activity and body composition. Although these factors have direct effects on BMD, the present study suggests that each may also influence BMD by modulating the activity of IL‐1β. Supported by NIH grant AG027714.