Developments in the pharmacotherapeutic management of osteoporosis.
During the last two decades, several medications have been granted a marketing authorisation for the management of osteoporosis. Bisphosphonates are the most widely prescribed drugs in this area, worldwide. Alendronate and risedronate are given daily or weekly and have demonstrated their ability to reduce fracture rates at the spine and hip. Ibandronate has demonstrated spine antifracture efficacy with intervals between dosings greater than weekly. New developments in this class include intravenous administration of ibandronate or zoledronate, once every three months or once yearly. Raloxifene, a selective estrogen-receptor modulator, reduces spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects. New selective estrogen-receptor modulators, including lasofoxifene, bazedoxifene and arzoxifene, are expected to demonstrate antifracture efficacy at the hip level, whilst retaining the extra-skeletal benefits (such as in the breast) that are obtained with raloxifene. The peptides from the parathyroid hormone family are potent stimulators of bone formation. Teriparatide (1 - 34 amino acid fragment of the parathyroid hormone) reduces spine and non-spine fractures, an effect that is sustained for up to 30 months after the withdrawal of treatment. The intact hormone (1 - 84 amino acids) showed similar results on spine fractures, and more data are requested to evaluate its effect on non-spine or hip fractures. Strontium ranelate is suggested to be the first medication to uncouple bone formation from bone resorption. It has shown antifracture efficacy at all sites in a large number of postmenopausal women. New developments include: denosumab, an antibody against receptor activator of NF-kappaB ligand (RANKL); a cytokine that is responsible for osteoclastogenesis; and inhibitors of cathepsin K, a cysteine protease that is involved in the cleavage of collagen.
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Pierre
P
Department of Public Health, Epidemiology and Health Economics, CHU Sart Tilman, University of Liège, Liège--Belgium.
Neuprez
Audrey
A
Reginster
Jean-Yves
JY
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069448:Denosumab; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006620:Hip Fractures / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D015201:Meta-Analysis as Topic; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D017410:Practice Guidelines as Topic; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D053245:RANK Ligand; D016032:Randomized Controlled Trials as Topic; D053246:Receptor Activator of Nuclear Factor-kappa B; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control*; D019379:Teriparatide / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D002352:Carrier Proteins; D004164:Diphosphonates; D008562:Membrane Glycoproteins; D009942:Organometallic Compounds; D011480:Protease Inhibitors; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D020845:Selective Estrogen Receptor Modulators; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D013876:Thiophenes; C081587:strontium ranelate; D019379:Teriparatide; D000069448:Denosumab; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K