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. © 2011 American Society for Bone and Mineral Research