Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin of Postmenopausal Women With Low Bone Mass

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 \[CTX\]).