Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review

PLoS One. 2013 Sep 4;8(9):e72714. doi: 10.1371/journal.pone.0072714. eCollection 2013.


Objective: Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment.

Methods: Literature databases were searched from inception to the 30th June 2012 for clinical trials of bisphosphonates to treat OA pain. Data was appraised and levels of evidence determined qualitatively using best evidence synthesis from the Cochrane Collaboration. The two largest studies were conducted with risedronate in the treatment of knee OA, for which meta-analyses were performed for pain and functional outcomes.

Results: Our searches found 13/297 eligible studies, which included a total of 3832 participants. The trials recruited participants with OA of the hand (n=1), knee (n=8), knee and spine (n=3), or hip (n=1). Our meta-analysis of the two largest knee studies using risedronate 15 mg showed odds ratios favouring placebo interventions for the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (1.73), WOMAC function (2.03), and WOMAC stiffness (1.82). However, 8 trials (61.5%) reported that bisphosphonates improve pain assessed by VAS scores and 2 (38.5%) reported significant improvement in WOMAC pain scores compared to control groups.

Conclusions: There is limited evidence that bisphosphonates are effective in the treatment of OA pain. Limitations of the studies we analysed included the differences in duration of bisphosphonate use, the dose and route of administration and the lack of long-term data on OA joint structure modification post-bisphosphonate therapy. Future more targeted studies are required to appreciate the value of bisphosphonates in treating osteoarthritis pain.

Trial registration: PROSPERO Register CRD42012002541.

Publication types

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

MeSH terms

  • Bone Density Conservation Agents / therapeutic use*
  • Diphosphonates / therapeutic use*
  • Humans
  • Osteoarthritis / drug therapy*
  • Pain / drug therapy*
  • Treatment Outcome


  • Bone Density Conservation Agents
  • Diphosphonates

Grant support

This work was supported by The Rosetrees' Trust, the National Institute for Health Research (NIHR) Comprehensive Local Research Network (CLRN), and The Wellcome Trust Value in People Award to Alison Davis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.