Zoledronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis.

Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown. The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers. We conducted a prospective intervention study in an ambulatory care setting. Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo. At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured. Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group. Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.