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 μg 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.
RCT Entities:
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 μg 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.
Authors: Pouneh K Fazeli; Irene S Wang; Karen K Miller; David B Herzog; Madhusmita Misra; Hang Lee; Joel S Finkelstein; Mary L Bouxsein; Anne Klibanski Journal: J Clin Endocrinol Metab Date: 2014-01-23 Impact factor: 5.958
Authors: S Piemonte; E Romagnoli; C Bratengeier; W Woloszczuk; A Tancredi; J Pepe; C Cipriani; S Minisola Journal: J Endocrinol Invest Date: 2012-07-24 Impact factor: 4.256