Regulation of circulating sclerostin levels by sex steroids in women and in men

Ulrike Il Mödder, Jackie A. Clowes, Kelley Hoey, James M. Peterson, Louise McCready, Merry Jo Oursler, B. Lawrence Riggs, Sundeep Khosla

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Sex steroids are important regulators of bone turnover, but the mechanisms of their effects on bone remain unclear. Sclerostin is an inhibitor of Wnt signaling, and circulating estrogen (E) levels are inversely associated with sclerostin levels in postmenopausal women. To directly test for sex steroid regulation of sclerostin levels, we examined effects of E treatment of postmenopausal women or selective withdrawal of E versus testosterone (T) in elderly men on circulating sclerostin levels. E treatment of postmenopausal women (n = 17) for 4 weeks led to a 27% decrease in serum sclerostin levels [versus +1% in controls (n = 18), p < .001]. Similarly, in 59 elderly men, we eliminated endogenous E and T production and studied them under conditions of physiologic T and E replacement, and then following withdrawal of T or E, we found that E, but not T, prevented increases in sclerostin levels following induction of sex steroid deficiency. In both sexes, changes in sclerostin levels correlated with changes in bone-resorption, but not bone-formation, markers (r = 0.62, p < .001, and r = 0.33, p = .009, for correlations with changes in serum C-terminal telopeptide of type 1 collagen in the women and men, respectively). Our studies thus establish that in humans, circulating sclerostin levels are reduced by E but not by T. Moreover, consistent with recent data indicating important effects of Wnts on osteoclastic cells, our findings suggest that in humans, changes in sclerostin production may contribute to effects of E on bone resorption.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalJournal of Bone and Mineral Research
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • BONE TURNOVER
  • ESTROGEN
  • SCLEROSTIN
  • TESTOSTERONE

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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