The Waning of Teriparatide Effect on Bone Formation Markers in Postmenopausal Osteoporosis Is Associated with Increasing Serum Levels of DKK1

Context: The effect of teriparatide (TPD) on bone turnover is initially exuberant but then diminishes. TPD is thought to stimulate bone formation by down-regulating the expression of specific Wnt antagonists, such as of sclerostin and Dickkopf-1 (DKK1). Objective: Our objective was to determine whether long-term treatment with TPD is associated with increasing serum levels of either sclerostin or DKK1. Design and Setting: Ancillary observation was made of patients participating in a randomized clinical trial. Patients, Intervention, and Outcomes: Fifty-five women with postmenopausal osteoporosis were randomly allocated to treatment for 18 months with either TPD 20 mu g daily or placebo. Results: In the TPD group, both N-propeptide of type I collagen and C-terminal telopeptide of type I collagen rose significantly by 108 and 175% within the first 6 months. At month 18, the mean values decreased significantly compared with month 12 (-10 and -12%, respectively), but they were still significantly higher than baseline (+84 and 152%, respectively). Sclerostin remained stable over the entire study period in both groups. DKK1 did not change during the first 6 month of treatment, but only in the active group, it rose significantly at month 12 (median change +26.9%) and remained elevated at month 18 (+29.7%), at the time when the pharmacological effect of treatment with TPD appeared to be declining. Conclusion: Long-term (> 12 months) treatment with TPD is associated with an increase in serum levels of DKK1 that might be associated with the appearance of declining effect on bone formation markers. (J Clin Endocrinol Metab 96: 1555-1559, 2011)