The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/β-catenin signalling. We compared the effects of two bisphosphonate treatments on two Wnt inhibitors sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 72 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100 mg/week (CLO) (n=36), yearly i.v. therapy with 5 mg zoledronate (ZOL) (n=16) and placebo (n=20). Bone turnover markers (intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, vs both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12 months of treatment both vs placebo group (P<0.005), baseline (P<0.001) and ZOL treated group. In the ZOL group, DKK1 levels increased significantly within one month and for the following 6 months and it fell back to baseline values at 12 months. The second ZOL infusion was again associated with an increase in DKK1 a month later, although to a lesser extent. In conclusion, in this study we have found that the treatment of postmenopausal osteoporosis with intermittent yearly ZOL is associated with transient and declining increases in DKK1 while continuous treatment with CLO, results in a progressive increase in serum SOST. These preliminary results and further ad hoc studies might contribute to shed light on our understanding of the bone coupling effects taking place during treatment of osteoporosis with different anti-resorbers or with different treatment regimens.
17 May 2014 - 20 May 2014