Serum Sclerostin Levels Negatively Correlate with Parathyroid Hormone Levels and Free Estrogen Index in Postmenopausal Women

Context: Sclerostin is a negative regulator of bone formation. Objective: The aim of the study was to compare serum sclerostin levels in premenopausal and postmenopausal women and evaluate its relationship to estrogen, TH, bone turnover, and bone mass. Design, Setting, and Participants: We conducted a cross-sectional observational study of healthy community-dwelling pre- and postmenopausal women. Intervention(s): There were no interventions. Main Outcome Measure(s): We compared serum sclerostin levels in pre- and postmenopausal women and correlated sclerostin levels with female sex hormones, calciotropic hormones, bone turnover markers, and bone mineral density. Results: Premenopausal women were 26.8 yr old, and postmenopausal women were 56.8 yr old. Postmenopausal women had lower values for estradiol (30 +/- 23 vs. 10 +/- 4 pg/ml; P < 0.001), estrone (61 +/- 24 vs. 29 +/- 10 pg/ml; P < 0.001), and free estrogen index (FEI) (6 +/- 4 vs. 3 +/- 2 pmol/nmol; P = 0.008) and significantly lower bone mineral density at all sites compared to premenopausal women, with no significant differences in levels of PTH, 25-hydroxy or 1,25-dihydroxy vitamin D levels. Postmenopausal women had significantly higher serum sclerostin levels (1.16 +/- 0.38 ng/ml vs. 0.48 +/- 0.15 ng/ml; P < 0.001). Because most of the premenopausal women were on oral contraceptives, subsequent analyses were limited to postmenopausal women. There were significant negative correlations between sclerostin and FEI and sclerostin and PTH in this group. Using multiple regression analysis, both FEI (beta = - 0.629; P = 0.002) and PTH (beta = -0.554; P = 0.004) were found to be independent predictors of sclerostin levels in postmenopausal women. Conclusions: Our findings suggest that serum sclerostin levels are regulated by both estrogens and PTH in postmenopausal women. These findings need to be explored further in larger prospective studies. (J Clin Endocrinol Metab 95: 1991-1997, 2010)