title: [Present and future of the treatment of osteoporosis with monoclonal antibodies].
abstract: An improved knowledge of bone physiopathology has led to new therapeutic targets in osteoporosis, blocking some of them with monoclonal antibodies. The RANK-RANKL-OPG system is considered the final effector pathway of bone resorption regulating factors. Denosumab is a humanized monoclonal antibody (IgG2) with a high affinity for RANKL. Upon binding RANKL it simulates the action of OPG, impedes the interaction between RANK-RANKL, blocks osteoclast activation and inhibits bone resorption. Denosumab has shown, in several phase III trials, to be a rapid, potent and safe antiresorptive agent. When administered subcutaneously every 6 months, it increases bone mineral density and is accompanied by a fast reduction in bone remodeling markers. According to the FREEDOM trial, in postmenopausal women with osteoporosis, treatment with 60 mg/sc of denosumab every 6 months for 3 years is accompanied by a reduction in the relative risk of fracture of 68% (incidence 2,3% in patients treated with denosumab and 7,2% in the placebo group), 20% in the case of non vertebral fractures (incidence 6,5% with denosumab vs. 8% with placebo) and 40% in hip fractures (incidence 0,7% with denosumab vs. 1,2% with placebo). It is a safe drug, with a frequency of adverse events similar to placebo, although an increased risk for skin reactions. Research is being done into blocking the Wnt/β-catenin pathway with monoclonal antibodies, specifically antisclerostin antibodies and anti-Dkk antibodies. This block of the Wnt/β-catenin pathway would have an anabolic action on bone remodeling.
authors.affiliation: Unidad de Reumatología, Hospital Universitari Son Espases, Palma de Mallorca, España. 26824jfa@comb.es
authors.forename: Jordi
authors.initials: J
authors.lastname: Fiter Aresté
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000069448:Denosumab; D005544:Forecasting; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy*; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab