title: A decade of bisphosphonate bone complications: what it has taught us about bone physiology.
abstract: While the AIDS epidemic of the 1980s taught the medical and dental professions much about immune cells and the immune system's cellular relationships, the bisphosphonate-induced osteonecrosis epidemic of the past decade has taught these same professions much about bone turnover, bone cell cross talk, the response and functional relationship of bone cells to loading, and drug effects on cellular dynamic relationships. The present article explores the literature as well as both evidence- and experience-based data to discuss known bone pathologies and physiologic mechanisms as well as uncover new findings: (1) bone remodeling is the mechanism by which bone adapts to loading stresses, termed either bone modeling or Wolff's law, and it is also the mechanism for bone renewal; (2) osteoclastic bone resorption triggers bone renewal at a rate of about 0.7%/day by its release of growth factors; (3) bisphosphonates prevent the renewal of old and injured bone, thus making it brittle and more likely to fracture over time; (4) bisphosphonates have a half-life in bone of 11 years because of their irreversible binding to bone via their central carbon atom; (5) when administered intravenously, bisphosphonate loads bone and accumulates in bone 142.8 times faster than when administered orally; (6) osteoclastic resorption of bisphosphonate-loaded bone results in osteoclast death in which the cell bursts, releasing the bisphosphonate molecules to reenter the local bone or bone marrow in a re-dosing effect; (7) endosteal osteoblasts are dependent on the osteoclastic resorption/growth factor release/new bone formation mechanism of bone renewal, whereas periosteal osteoblasts are not; and (8) it is likely that endosteal osteoblasts and periosteal osteoblasts have different cell membrane receptors and arise from separate embryologic niches.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marx
mesh_terms: D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates