How to grow bone to treat osteoporosis and mend fractures.
There is a need for "anabolic" drugs that can directly stimulate bone growth, improve bone microarchitecture, accelerate fracture healing, and, thus, restore bone strength to osteoporosis patients and, hopefully, regenerate eroded bone in arthritis patients. The anabolic agents currently leading the way to the clinic are the parathyroid hormone (PTH) and some of its adenylyl cyclase-stimulating fragments. This article is a summary of what is known about how PTHs stimulate bone growth. The controversial bone anabolic activities of the cholesterol-lowering lipophilic statins are also described, and mechanisms by which they may stimulate bone growth are presented. Finally, evidence is presented for the body's "fat-o-stat" cytokine--leptin--indirectly restraining bone growth via a hypothalamic factor, while at the same time serving as a local PTH-like autocrine/paracrine stimulator of osteoblast activity, as well as an inhibitor of osteoclast generation.
Whitfield
James F
JF
Institute for Biological Sciences, National Research Council of Canada, Montreal Road Campus, Building M-54, Ottawa, Ontario K1A 0R6, Canada. pthosteo@rogers.com
D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D050723:Fractures, Bone / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020738:Leptin; D010281:Parathyroid Hormone