Bone Turnover across the Menopause Transition: Correlations with Inhibins and Follicle-Stimulating Hormone

Abstract

Context:Longitudinal clinical studies demonstrate that increases in bone turnover that occur in perimenopausal women correlate better with elevated serum FSH than with changes in serum estradiol (E2). This perimenopausal rise in FSH is due to a selective decrease in ovarian inhibin B (InhB). Our previous demonstration that inhibins suppress both osteoblast and osteoclast development suggests that changes in serum inhibins may regulate osteoblast and osteoclast differentiation and thereby bone turnover, independent of changes in sex steroids.Objective: The objective of this study was to determine whether decreased serum inhibin A (InhA) and InhB levels correlate with increases in markers of bone turnover in women across the menopause transition and to evaluate serum inhibins as better predictors of bone turnover markers across the menopause transition than FSH or bioavailable E2. Design:We studied a cross-sectional age-stratified population sample of 188 pre-and postmenopausal women not using oral contraceptives or hormone replacement therapy (age, 21-85 yr).Results: Serum InhA and InhB levels significantly correlated inversely with markers of bone formation and bone resorption in preand perimenopausal women and with markers of bone formation in postmenopausal women (InhA only). FSH was not significantly correlated with bone turnover in either pre-or postmenopausal women; however, FSH was significantly correlated with bone resorption (Cterminal collagen I cross-link) in perimenopausal women (age, 45-54 yr). Using multivariate analyses, serum InhA better predicted bone formation and resorption markers in premenopausal women than either FSH or bioavailable E2. I T IS WIDELY accepted that estrogen plays a critical role in the maintenance of bone homeostasis and that the cellular basis of bone loss in postmenopausal women results from derepression of both osteoblast and osteoclast development (1). The pathophysiology of postmenopausal osteoporosis involves the overproduction of osteoclasts relative to the integrally coupled increase in osteoblastogenesis, a process that also facilitates osteoclast development (2-4). ConclusionsEstrogen deficiency has been identified as a major risk factor for osteoporosis in women (1,5,6). Recent evidence suggests that estrogen deficiency may be responsible, not only for the rapid bone loss of the early postmenopausal phase, but may also be involved in the later slower phase of bone loss associated with aging (5,7,8). However, in late premenopausal women with normal circulating estrogen levels, clinical indices of increased bone turnover are already elevated (9). In fact, the endocrine parameter best correlated with increases in bone turnover in a large cohort of perimenopausal women is elevated serum FSH levels (9). Studies in perimenopausal women have demonstrated that the mechanism involved in this early rise in FSH is a selective decrease in inhibin B (InhB) secretion in the presence of normal levels of estradiol (E2), inhibin A (InhA), GnRH, and LH (10, 11). Because both InhA a...

Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation

“…In another study, plasma levels of inhibin correlate with bone mass more strongly than with FSH (22). The relationship between hormone levels and bone mass might simply be correlative rather than causal.…”

New targets for old hormones: inhibins clinical role revisited [Review]

“…The mechanism of all these actions was often correlated with blocking action on bone morphogenetic proteins effect on osteoblastogenesis and osteoclastogenesis. Subsequently, the confirmation of these actions in human cells provided further evidence that changes in ovarian inhibins might directly influence bone turnover via changes in cell differentiation [97]. Clinical studies in peri-menopausal women that measured serum circulating levels of steroids, inhibins and FSH confirmed that decrease in inhibin levels across the menopausal transition is associated with increasing bone turnover as well as with bone mass regardless of changes in steroids or FSH levels [95,97,98] (Fig.…”

Evaluation of the height of premenopausal and postmenopausal women in Zaria, Nigeria

“…It has been suggested by a study that elevated serum FSH accelerates bone loss directly (Sowers et al, 2006). Other contributors to menopausal bone loss include, low progesterone levels, and decreases in serum inhibin concentrations (Perrien et al, 2006;Prior, 1990).…”