Implications of osteoblast-osteoclast interactions in the management of osteoporosis by antiresorptive agents denosumab and odanacatib.
Antiresorptive agents, used in the treatment of osteoporosis, inhibit either osteoclast formation or function. However, with these approaches, osteoblast activity is also reduced because of the loss of osteoclast-derived coupling factors that serve to stimulate bone formation. This review discusses how osteoclast inhibition influences osteoblast function, comparing the actions of an inhibitor of osteoclast formation [anti-RANKL/Denosumab (DMAB)] with that of a specific inhibitor of osteoclastic cathepsin K activity [Odanacatib (ODN)]. Denosumab rapidly and profoundly, but reversibly, reduces bone formation. In contrast, preclinical studies and clinical trials of ODN showed that bone formation at some skeletal sites was preserved although resorption was reduced. This preservation of bone formation appears to be due to effects of coupling factors, secreted by osteoclasts and released from demineralized bone matrix. This indicates that bone resorptive activities of osteoclasts are separable from their coupling activities.
Bone Cell Biology and Disease Unit, St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria, 3065, Australia, nsims@svi.edu.au.
Natalie A
NA
Sims
Kong Wah
KW
Ng
D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects; D056657:Cathepsin K / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D000069448:Denosumab; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy; D053245:RANK Ligand / Q000037:antagonists & inhibitors
D061067:Antibodies, Monoclonal, Humanized; D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D000069448:Denosumab; D056657:Cathepsin K; C527128:odanacatib