Antiresorptive agents and osteoclast apoptosis.
Antiresorptive agents have proven to be effective therapies for the treatment of bone diseases associated with excessive osteoclast activity. Decreased osteoclast formation, inhibition of osteoclast actions, and reduced osteoclast survival represent mechanisms by which antiresorptive agents could act. The goals of this article are to present the evidence that antiresorptive agents can decrease osteoclast survival through apoptosis, to review the mechanisms by which they are thought to activate the apoptotic process, and to consider whether the actions on apoptosis fully account for the antiresorptive effects. As background, the apoptotic process will be briefly summarized together with the evidence that factors that promote osteoclast survival affect steps in the process. Following this, therapeutic agents that are both antiresorptive and can stimulate osteoclast apoptosis will be discussed. Other bone therapeutic agents that are either antiresorptive or apoptotic, but not both, will be described. Finally, newer antiresorptive compounds that elicit apoptosis and could represent potential therapeutic agents will be noted.
Stern
Paula H
PH
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. p-stern@northwestern.edu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D065095:Calcineurin Inhibitors; D002116:Calcitonin / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*
D050071:Bone Density Conservation Agents; D065095:Calcineurin Inhibitors; D002116:Calcitonin