Sclerostin and DKK1 in postmenopausal osteoporosis treated with Denosumab.

INTRODUCTION: The bone mass benefits of anti-resorbers in postmenopausal osteoporosis are limited by the rapid coupling of decreasing bone resorption with bone formation. The Wnt signalling is involved in this coupling process during treatment with bisphosphonates, while its role during treatment with the anti receptor activator of nuclear factor kappa B ligand (RANKL)antibodies, Denosumab is unknown.METHODS: The study population includes patients participating in a placebo controlled trial lasting 36 months: 19 women were on placebo and 24 on subcutaneous 60 mg Denosumab every 6months.RESULTS: All measured parameters (serum C-terminal telopeptide of type I collagen [sCTX], serum bone alkaline phosphatase [bAP], Dickkopf-1 (DKK1) and sclerostin) remained unchanged during the observation period in the placebo group. sCTX and bAP were significantly suppressed by Denosumab treatment over the entire follow-up. Denosumab treatment was associated with significant (p<0.05) increases (28-32%) in serum sclerostin over the entire study follow-up. Serum DKK1 significantly decreased within the first 6 months with a trend for further continuous decreases which reached statistical significance (P<0.05) versus placebo group from the 18th monthonward. The changes in DKK1 were significantly and positively related with the changes in sCTX and bAP and negatively with hip BMD changes. The changes in sclerostin were significantly andnegatively related only with those of bAP.CONCLUSION: The changes in bone turnover markers associated with Denosumab treatment of postmenopausal osteoporosis are associated with significant increase in sclerostin similar to thoseseen after long term treatment with bisphosphonates, and significant decrease in DKK1. This latter observation might explain the continuous increase over 5 years in BMD observed during treatment of postmenopausal osteoporosis with Denosumab.