CONTEXT: Decreased bone formation due to a coupling effect limits bone mass increases after antiresorptive treatment. OBJECTIVE: The purpose of this study was to compare the effects of 2 potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf-1 (Dkk-1). DESIGN: This was an interventional, parallel assignment, open-label, randomized clinical trial. SETTING: The study was conducted at the outpatient clinics for metabolic bone diseases of 424 General Military Hospital, Thessaloniki, Greece. PATIENTS AND INTERVENTIONS:Naive postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n = 46) or denosumab injection (n = 46). One woman in the zoledronic acid group was lost to follow-up. MAIN OUTCOME MEASURES: Serum sclerostin and Dkk-1 levels were the main outcomes. Secondary measurements were serum osteoprotegerin, receptor activator of nuclear factor κB ligand, procollagen type 1 N-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen. RESULTS:Serum sclerostin levels significantly decreased in the zoledronic acid (P < .001) but increased in the denosumab group (P = .003). Dkk-1 levels significantly decreased in the zoledronic acid group (P = .006) but did not change in the denosumab group (P = .402). Serum osteoprotegerin remained essentially unchanged in either group, whereas receptor activator of nuclear factor κB ligand decreased in the zoledronic acid group (P = .004) but increased in the denosumab group (P = .037). Bone markers (procollagen type 1 N-terminal propeptide, C-terminal cross-linking telopeptide of type 1 collagen, and total serum alkaline phosphatase) decreased in both groups (all P < .001). CONCLUSIONS: Although they both decrease bone resorption, zoledronic acid and denosumab exert opposite effects on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, whereas the latter increases sclerostin and does not affect Dkk-1.
RCT Entities:
CONTEXT: Decreased bone formation due to a coupling effect limits bone mass increases after antiresorptive treatment. OBJECTIVE: The purpose of this study was to compare the effects of 2 potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf-1 (Dkk-1). DESIGN: This was an interventional, parallel assignment, open-label, randomized clinical trial. SETTING: The study was conducted at the outpatient clinics for metabolic bone diseases of 424 General Military Hospital, Thessaloniki, Greece. PATIENTS AND INTERVENTIONS: Naive postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n = 46) or denosumab injection (n = 46). One woman in the zoledronic acid group was lost to follow-up. MAIN OUTCOME MEASURES: Serum sclerostin and Dkk-1 levels were the main outcomes. Secondary measurements were serum osteoprotegerin, receptor activator of nuclear factor κB ligand, procollagen type 1 N-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen. RESULTS: Serum sclerostin levels significantly decreased in the zoledronic acid (P < .001) but increased in the denosumab group (P = .003). Dkk-1 levels significantly decreased in the zoledronic acid group (P = .006) but did not change in the denosumab group (P = .402). Serum osteoprotegerin remained essentially unchanged in either group, whereas receptor activator of nuclear factor κB ligand decreased in the zoledronic acid group (P = .004) but increased in the denosumab group (P = .037). Bone markers (procollagen type 1 N-terminal propeptide, C-terminal cross-linking telopeptide of type 1 collagen, and total serum alkaline phosphatase) decreased in both groups (all P < .001). CONCLUSIONS: Although they both decrease bone resorption, zoledronic acid and denosumab exert opposite effects on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, whereas the latter increases sclerostin and does not affect Dkk-1.
Authors: A D Anastasilakis; S A Polyzos; A Gkiomisi; Z G Saridakis; D Digkas; I Bisbinas; G T Sakellariou; A Papatheodorou; P Kokkoris; P Makras Journal: Osteoporos Int Date: 2015-05-20 Impact factor: 4.507
Authors: Ioannis Kyvernitakis; Tilman D Rachner; Anja Urbschat; Olaf Hars; Lorenz C Hofbauer; Peyman Hadji Journal: J Cancer Res Clin Oncol Date: 2014-06-07 Impact factor: 4.553
Authors: David W Dempster; Hua Zhou; Robert R Recker; Jacques P Brown; Christopher P Recknor; E Michael Lewiecki; Paul D Miller; Sudhaker D Rao; David L Kendler; Robert Lindsay; John H Krege; Jahangir Alam; Kathleen A Taylor; Boris Janos; Valerie A Ruff Journal: J Clin Endocrinol Metab Date: 2016-02-09 Impact factor: 5.958