Bisphosphonates: mechanism of action and role in clinical practice

Mayo Clin Proc. 2008 Sep;83(9):1032-45. doi: 10.4065/83.9.1032.


Bisphosphonates are primary agents in the current pharmacological arsenal against osteoclast-mediated bone loss due to osteoporosis, Paget disease of bone, malignancies metastatic to bone, multiple myeloma, and hypercalcemia of malignancy. In addition to currently approved uses, bisphosphonates are commonly prescribed for prevention and treatment of a variety of other skeletal conditions, such as low bone density and osteogenesis imperfecta. However, the recent recognition that bisphosphonate use is associated with pathologic conditions including osteonecrosis of the jaw has sharpened the level of scrutiny of the current widespread use of bisphosphonate therapy. Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / pharmacology*
  • Bone Resorption / drug therapy
  • Bone and Bones / drug effects
  • Breast Neoplasms / drug therapy
  • Diphosphonates / administration & dosage
  • Diphosphonates / pharmacology*
  • Female
  • Humans
  • Male
  • Multiple Myeloma / drug therapy
  • Osteitis Deformans / drug therapy*
  • Osteoclasts / drug effects*
  • Osteoporosis / drug therapy*
  • Prostatic Neoplasms / drug therapy


  • Bone Density Conservation Agents
  • Diphosphonates