Bone turnover across the menopause transition: Correlations with inhibins and follicle-stimulating hormone

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 pre- and 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 (C-terminal 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. Conclusions: Decreases in inhibin levels across the menopause transition are associated with increasing bone turnover, regardless of changes in sex steroids or FSH.