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- Title
Bone turnover across the menopause transition.
- Authors
Nicks, Kristy M.; Fowler, Tristan W.; Akel, Nisreen S.; Perrien, Daniel S.; Suva, Larry J.; Gaddy, Dana
- Abstract
Accumulating evidence demonstrates increasing bone turnover and bone loss in women prior to menopause and decreases in serum estradiol levels. Increased follicle-stimulating hormone levels have been correlated with some of these peri-menopausal changes. However, decreases in gonadal inhibins of the transforming growth factor (TGF)-β superfamily strongly correlate with increases in bone formation and resorption markers across the menopause transition and predict lumbar bone mass in peri-menopausal women, likely as a result of direct inhibin suppression of osteoblastogenesis and osteoclastogenesis. Inhibins bind specifically to cells during osteoblastogenesis and osteoclastogenesis. They can block bone morphogenetic protein (BMP)-stimulated osteoblast and osteoclast development as well as BMP-stimulated SMAD1 phosphorylation, likely via inhibin–β-glycan sequestration of BMP Type II receptor (BMPRII). Interestingly, continuous in vivo exposure to inhibin A is anabolic and protective against gonadectomy-induced bone loss in mice, suggesting that inhibins contribute to the endocrine regulation of bone metabolism via a bimodal mechanism of action whereby cycling inhibin exposure suppresses bone turnover and continuous exposure to inhibins is anabolic.
- Subjects
MENOPAUSE; FOLLICLE-stimulating hormone; PERIMENOPAUSE; TRANSFORMING growth factors; OSTEOCLASTS; PHOSPHORYLATION
- Publication
Annals of the New York Academy of Sciences, 2010, Vol 1192, Issue 1, p153
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.2009.05349.x