Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin of Postmenopausal Women With Low Bone Mass (DenoZol)
The primary aim of the study is the comparative effect of zolendronic acid versus denosumab on serum sclerostin levels in postmenopausal women with low bone mass.
Secondary aims are their comparative effect on serum dickkopf-1, osteoprotegerin, receptor activator of nuclear factor kappaB ligand (RANKL) and bone turnover markers (procollagen type I N-terminal peptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]).
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin Levels of Postmenopausal Women With Low Bone Mass: A Multicenter, Randomized, Head-to-head Clinical Trial|
- Sclerostin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Serum sclerostin levels
- Dickkopf-1 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Serum dickkopf-1 (DKK-1) levels
- OPG/RANKL [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Serum osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) levels
- Calcium metabolism [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Serum calcium, phosphate, intact parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD)
- Bone turnover [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Serum bone turnover markers (total alkaline phosphatase [TSAP], type I N-terminal peptides [PINP] και C-terminal cross-linking telopeptide of type I collagen [CTX])
|Study Start Date:||April 2012|
|Study Completion Date:||January 2013|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
Denosumab (injection), 60 mg, administered as a single subcutaneous injection once
Other Name: Prolia
|Experimental: Zoledronic Acid||
Drug: Zoledronic acid
Zoledronic acid (vial), 5 mg, administered once as a single 15- to 30-minute intravenous infusion
Other Name: Aclasta
Osteoporosis is the most common bone disease, caused by a relatively increased rate of bone resorption by the osteoclasts that exceeds the rate of bone formation by the osteoblasts, resulting in net loss of bone mass. To-date, antiresorptive agents, which inhibit osteoclast activity and induce their apoptosis, are considered as the cornerstone of osteoporosis prevention and treatment.
Bisphosphonates currently represent the first line antiresorptive agents for the management of postmenopausal osteoporosis. Zoledronic acid is considered to-date the most potent bisphosphonate. A once-yearly infusion of intravenous zoledronic acid decreases bone turnover, improves bone density and decreases the vertebral and non-vertebral fracture risk.
Most recently, denosumab (AMG-162) has been launched for the treatment of postmenopausal osteoporosis. Denosumab, a fully human monoclonal IgG2 antibody against human RANKL, specifically binds and neutralizes the receptor activator of nuclear factor kappaB ligand (RANKL) in order to decrease bone resorption and subsequent bone loss. Subcutaneous administration of denosumab every six months decreases bone turnover markers, increases bone mineral density and reduces the vertebral and non-vertebral fracture risk.
The role of sclerostin in bone metabolism is emerging. Sclerostin is the secreted expression of the SOST gene. In adult human bone, sclerostin is expressed only by osteocytes and inhibits bone formation by osteoblasts. It has been proposed that sclerostin expression by newly embedded osteocytes at the onset of osteoid mineralization may serve as a negative feedback signal on osteoblasts to prevent overfilling of the basic multicellular unit.
Although zoledronic acid and denosumab are currently regarded as the most potent antiresorptive agents, there is no head-to-head comparative study. This study primarily aims to the comparative effect of zoledronic acid and denosumab on serum sclerostin levels and secondarily on serum dickkopf-1, osteoprotegerin, RANKL and bone turnover markers (procollagen type I N-terminal peptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]).
|251 Hellenic Air Force Hospital|
|Athens, Attikis, Greece|
|Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital|
|424 General Military Hospital|
|Principal Investigator:||Stergios A Polyzos, MD, MSc, PhD||Aristotle University Of Thessaloniki|
|Principal Investigator:||Athanasios D Anastasilakis, MD, PhD||424 General Military Hospital|
|Principal Investigator:||Polyzois Makras, MD, PhD||251 Hellenic Air Force Hospital|