New treatment targets in osteoporosis.
Postmenopausal osteoporosis is characterized by bone remodeling alterations with an imbalance between excessive bone resorption and inadequate bone formation. At present, osteoporosis treatment rests on bone resorption inhibitors and, more specifically, on bisphosphonates. However, the introduction of anabolic agents such as parathyroid hormone that stimulate bone formation has expanded the range of treatment options. New treatment targets have been identified via improved knowledge on bone pathophysiology, bone remodeling, bone cells and intracellular signaling pathways. RANKL inhibition by anti-RANKL antibodies is undergoing considerable development as a treatment for osteoporosis. Also under development are anti-catabolic drugs that target the molecular mechanisms involved in bone resorption, including cathepsin K inhibitors and integrin alpha(v)beta(3) antagonists. The identification of new pathways involved in bone formation is directing clinical research efforts toward the development of anabolic agents. The signaling pathways involved in bone formation, most notably the Wnt-pathway, hold considerable promise as treatment targets in conditions characterized by insufficient bone formation. Current focuses of interest include antibodies against naturally occurring Wnt-pathway antagonists (e.g., sclerostin and Dkk1) and modulators of parathyroid hormone production (calcilytic agents). Thus, active research is ongoing to improve the treatment of osteoporosis, a disease whose high prevalence and considerable functional and socioeconomic impact will raise formidable challenges in the near future.
Roux
Sophie
S
Service de rhumatologie, département de médecine, université de Sherbrooke, 12(e) avenue Nord, 3001 Sherbrooke, QC, J1H 5N4, Canada. sophie.roux@usherbrooke.ca
D045930:Anabolic Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D056657:Cathepsin K / Q000037:antagonists & inhibitors; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors
D045930:Anabolic Agents; D018501:Antirheumatic Agents; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D051153:Wnt Proteins; C534130:CTSK protein, human; D056657:Cathepsin K