[Therapeutic innovation in osteoporosis (antisclerostin antibody and denosumab)].
Prevalence of osteoporosis, a systemic disease characterized by an impairment of bone mass, will continue to increase due to an ageing population and result in greater risks of fractures with disastrous medical and socioeconomic consequences. A better understanding of the regulation pathway of bone remodeling has led to the identification of new therapeutic targets. Denosumab, a monoclonal antibody against Receptor Activator of Nuclear factor κB-ligand (key molecule in osteoclastogenesis) is a fast-working, reversible antiresorptive treatment. A subcutaneous injection is required twice a year, a significant advantage over bisphosphonates whose efficiency is limited by an inadequate long-term compliance. The only anabolic agent currently available, Teriparatide (parathyroid hormone residues 1-34), administered daily via subcutaneous injection, stimulates both sides of bone remodeling in favour of bone formation. Anti-sclerostin antibodies neutralize an inhibitor of Wnt pathway, the master switch for osteoblastic differentiation, and meet the challenge of pioneering an anabolic drug that does not increase bone resorption. If the tolerance of these promising treatments is good in clinical trials of short duration, their implication in signaling pathways affecting various tissues means that one has to keep a very close watch on their long-term potential risks. Finally, the endocrinologists must be aware that the local regulating factors of bone remodeling recently identified (sclerostin, osteoprotegerin) seem to be the key mediators of hormones with bone tropism.
Service d'Endocrinologie, Diabète et Maladies Métaboliques, CHU de Grenoble. MAQuemerais@chu-grenoble.fr
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Quemerais-Durieu
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Kerlan
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Chabre
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D016723:Bone Remodeling / Q000187:drug effects; D002986:Clinical Trials as Topic; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010024:Osteoporosis / Q000188:drug therapy*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D053244:Osteoprotegerin / Q000378:metabolism; D010349:Patient Compliance; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D051381:Rats; D019379:Teriparatide / Q000627:therapeutic use; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005819:Genetic Markers; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; C422903:SOST protein, human; D019379:Teriparatide; D000069448:Denosumab