Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays

Can Fam Physician. 2014 Apr;60(4):324-33.


Objective: To outline the efficacy and risks of bisphosphonate therapy for the management of osteoporosis and describe which patients might be eligible for bisphosphonate "drug holiday."

Quality of evidence: MEDLINE (PubMed, through December 31, 2012) was used to identify relevant publications for inclusion. Most of the evidence cited is level II evidence (non-randomized, cohort, and other comparisons trials).

Main message: The antifracture efficacy of approved first-line bisphosphonates has been proven in randomized controlled clinical trials. However, with more extensive and prolonged clinical use of bisphosphonates, associations have been reported between their administration and the occurrence of rare, but serious, adverse events. Osteonecrosis of the jaw and atypical subtrochanteric and diaphyseal femur fractures might be related to the use of bisphosphonates in osteoporosis, but they are exceedingly rare and they often occur with other comorbidities or concomitant medication use. Drug holidays should only be considered in low-risk patients and in select patients at moderate risk of fracture after 3 to 5 years of therapy.

Conclusion: When bisphosphonates are prescribed to patients at high risk of fracture, their antifracture benefits considerably outweigh their potential for harm. For patients taking bisphosphonates for 3 to 5 years, reassess the need for ongoing therapy.

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
  • Diaphyses / injuries
  • Diphosphonates / adverse effects*
  • Diphosphonates / pharmacokinetics
  • Esophageal Neoplasms / chemically induced
  • Femoral Fractures / chemically induced
  • Humans
  • Osteoporosis / drug therapy*
  • Osteoporotic Fractures / prevention & control*
  • Renal Insufficiency / complications
  • Risk Assessment


  • Bone Density Conservation Agents
  • Diphosphonates