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Bone turnover across the menopause transition
Author(s) -
Nicks Kristy M.,
Fowler Tristan W.,
Akel Nisreen S.,
Perrien Daniel S.,
Suva Larry J.,
Gaddy Dana
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05349.x
Subject(s) - endocrinology , bone remodeling , medicine , osteoclast , anabolism , bone resorption , chemistry , osteoblast , endocrine system , paracrine signalling , osteoporosis , receptor , hormone , biology , in vitro , biochemistry
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.