Serum Sclerostin Increases in Healthy Adult Men during Bed Rest

Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. Design, Setting, and Participants: Seven healthy adult men (31 +/- 3 yr old) underwent 90 d of 6 head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean +/- SD. Results: Consistent with prior reports, bone mineral density declined significantly (1-2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 +/- 20%; P = 0.003) and BR-60 (+42 +/- 31%; P < 0.001), with a lesser increase at BR-90 (+22 +/- 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (-17 +/- 16%; P = 0.02) and BR-60 (-24 +/- 14%; P = 0.03) and remained lower than BL at BR-90 (-21 +/- 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased. (J Clin Endocrinol Metab 97: E1736-E1740, 2012)