Elevated serum concentrations of follicle-stimulating hormone (FSH) are associated with diminished bone density in women, beginning years before menopause and the decline in estradiol. We hypothesized that FSH promotes development of myeloid cells toward the bone-resorbing osteoclast phenotype. This was tested by isolating peripheral blood mononuclear cells from nine healthy adults, incubating them in the presence of FSH at three different concentrations spanning the physiological range, and then measuring the expression of receptor activator for NF-κB (RANK, a surface marker for osteoclasts) on CD14(+) cells by flow cytometry. In the absence of FSH, 3.3±0.5% of the cells expressed high levels of the receptor (RANK(high)). Increasing concentrations of FSH caused a biphasic dose-response, with a maximal (1.5-fold) increase in RANK(high) cells achieved with 50 mIU/ml FSH (P=0.02). Cytokines that influence development of osteoclasts were also measured in culture supernatants: macrophage colony stimulating factor (M-CSF), osteoprotegerin (OPG) and tumor necrosis factor-α (TNFα) concentrations were not significantly influenced by FSH, whereas RANK-ligand was undetectable. This study supports the concept that the elevated circulating concentrations of FSH during perimenopause may contribute to the increased rate of bone loss by promoting the development of osteoclast precursor cells.
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