Estrogen inhibits Dlk1/FA1 production: A potential mechanism for estrogen effects on bone turnover

We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s-Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (serum cross-linked C-telopeptide [s-CTX] and serum osteocalcin) were measured in two cohorts: a group of pre- and postmenopausal women (n=100) and a group of postmenopausal women, where half had received estrogen-replacement therapy (ERT, n=166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p<0.001). s-Dlk1/FA1 was correlated with s-CTX (r=0.30, p<0.01). ERT in postmenopausal women decreased s-Dlk1/FA1, as well as s-CTX and s-osteoclacin (all p<.0001). Changes in s-Dlk1 were significantly correlated with those observed in s-CTX (r=0.18, p<0.05) and s-osteocalcin (r=0.28, p<0.001). In conclusion, s-Dlk1/FA1 is influenced by E-deficiency and is correlated with bone turnover. Increased levels of s-Dlk1/FA1 in postmenopausal women may be a mechanism mediating the effects of estrogen deficiency on bone turnover.