Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday

Am J Med. 2013 Jan;126(1):13-20. doi: 10.1016/j.amjmed.2012.06.023. Epub 2012 Nov 20.


The amino-bisphosphonates are first-line therapy for the treatment of most patients with osteoporosis, with proven efficacy to reduce fracture risk at the spine, hip, and other nonvertebral skeletal sites. Further, bisphosphonates have been associated with a significant decrease in morbidity and increase in survival. Following the use of bisphosphonates in millions of patients in clinical practice, some unexpected possible adverse effects have been reported, including osteonecrosis of the jaw, atypical femur fractures, atrial fibrillation, and esophageal cancer. Because bisphosphonates are incorporated into the skeleton and continue to exert an antiresorptive effect for a period of time after dosing is discontinued, the concept of a drug holiday has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from antifracture efficacy. Patients receiving bisphosphonates who are not at high risk for fracture are potential candidates for a drug holiday, while for those with bone mineral density in the osteoporosis range or previous history of fragility fracture, the benefits of continuing therapy probably far outweigh the risk of harm.

Publication types

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

MeSH terms

  • Atrial Fibrillation / chemically induced
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / pharmacokinetics
  • Diphosphonates / adverse effects*
  • Diphosphonates / pharmacokinetics
  • Esophageal Neoplasms / chemically induced
  • Femoral Fractures / chemically induced
  • Fractures, Bone / prevention & control*
  • Humans
  • Osteoporosis / drug therapy*
  • Risk Assessment


  • Bone Density Conservation Agents
  • Diphosphonates