BACKGROUND: Osteoporosis is a prevalent condition that may lead to increased risks for bone fracture and other morbidities and increased health care costs. Treatment modalities for osteoporosis aim to prevent further bone loss and to reduce the risk for fracture. Denosumab is a human monoclonal antibody developed for use in osteoporosis. It inhibits the receptor activator of nuclear factor κB ligand, a cytokine that mediates osteoclast-mediated bone resorption. OBJECTIVE: The intent of this article was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, efficacy, and tolerability of denosumab in the prevention and treatment of postmenopausal osteoporosis. METHODS: The MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations databases were searched for English-language reviews, abstracts, presentations, and clinical trials of denosumab in humans, published from 1995 through July 2011. Search terms included denosumab, osteoporosis, RANK ligand, and bone resorption. Available data were evaluated, and relevant clinical data were selected for inclusion. RESULTS: Three Phase II and 4 Phase III studies that evaluated the efficacy of denosumab in postmenopausal women were identified. In a Phase III study, the percentage change from baseline in bone mineral density (BMD) was significantly greater with denosumab compared with placebo (+6.5% vs -0.6%, respectively; P < 0.0001). In another Phase III trial, the cumulative prevalence of vertebral fractures was significantly lower with denosumab compared with placebo (2.3% vs 7.2%; 95% CI, 0.26-0.41; P < 0.001). Denosumab treatment was associated with significantly greater changes in BMD at the total hip (+4.5% vs +3.4%; P < 0.0001) and distal radius (+1.1% vs +0.6%; P = 0.0001) compared with alendronate. Adverse events reported with the use of denosumab have included back pain (34.7%); pain in the extremities (11.7%); general musculoskeletal pain (7.6%); elevated cholesterol (7.2%); inflammation of the bladder (5.9%); and dermatologic conditions including dermatitis, eczema, and rashes (combined prevalence, 10.8%). Serious adverse events have included hypocalcemia (1.7%), pancreatitis (0.2%), and severe infection (0.2%). Several cases of osteonecrosis of the jaw have also been reported. CONCLUSIONS: Based on the data from the available literature, denosumab is an efficacious and well-tolerated treatment for postmenopausal osteoporosis.
BACKGROUND:Osteoporosis is a prevalent condition that may lead to increased risks for bone fracture and other morbidities and increased health care costs. Treatment modalities for osteoporosis aim to prevent further bone loss and to reduce the risk for fracture. Denosumab is a human monoclonal antibody developed for use in osteoporosis. It inhibits the receptor activator of nuclear factor κB ligand, a cytokine that mediates osteoclast-mediated bone resorption. OBJECTIVE: The intent of this article was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, efficacy, and tolerability of denosumab in the prevention and treatment of postmenopausal osteoporosis. METHODS: The MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations databases were searched for English-language reviews, abstracts, presentations, and clinical trials of denosumab in humans, published from 1995 through July 2011. Search terms included denosumab, osteoporosis, RANK ligand, and bone resorption. Available data were evaluated, and relevant clinical data were selected for inclusion. RESULTS: Three Phase II and 4 Phase III studies that evaluated the efficacy of denosumab in postmenopausal women were identified. In a Phase III study, the percentage change from baseline in bone mineral density (BMD) was significantly greater with denosumab compared with placebo (+6.5% vs -0.6%, respectively; P < 0.0001). In another Phase III trial, the cumulative prevalence of vertebral fractures was significantly lower with denosumab compared with placebo (2.3% vs 7.2%; 95% CI, 0.26-0.41; P < 0.001). Denosumab treatment was associated with significantly greater changes in BMD at the total hip (+4.5% vs +3.4%; P < 0.0001) and distal radius (+1.1% vs +0.6%; P = 0.0001) compared with alendronate. Adverse events reported with the use of denosumab have included back pain (34.7%); pain in the extremities (11.7%); general musculoskeletal pain (7.6%); elevated cholesterol (7.2%); inflammation of the bladder (5.9%); and dermatologic conditions including dermatitis, eczema, and rashes (combined prevalence, 10.8%). Serious adverse events have included hypocalcemia (1.7%), pancreatitis (0.2%), and severe infection (0.2%). Several cases of osteonecrosis of the jaw have also been reported. CONCLUSIONS: Based on the data from the available literature, denosumab is an efficacious and well-tolerated treatment for postmenopausal osteoporosis.
Authors: Rohinton S Tarapore; Jason Lim; Chen Tian; Sandra Pacios; Wenmei Xiao; Daniel Reid; Hancheng Guan; Marcelo Mattos; Bo Yu; Cun-Yu Wang; Dana T Graves Journal: J Bone Miner Res Date: 2015-08-06 Impact factor: 6.741