byAmerican College of Physicians

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A systematic review and meta-analysis has found that bisphosphonates—medicines commonly used to treat osteoporosis—may offer short-term pain relief for people with complex regional pain syndrome (CRPS), but the benefits are uncertain beyond the short term and side effects are likely. The study, the largest analysis of a CRPS treatment to date, ispublishedinAnnals of Internal Medicine.

CRPS is a severe and often disablingchronic paincondition that usually develops in a limb after injury or surgery. Effective treatments are extremely limited, and many patients experience persistent pain, disability and reductions in quality of life.

Researchers from the University of New South Wales Sydney, Neuroscience Research Australia, Brunel University London, University of Liverpool, and colleagues analyzed 11 randomized controlled trials (RCTs) involving 754 adults with CRPS to determine the benefits and harms of bisphosphonates for CRPS.

The included evidence evaluated five bisphosphonate types given orally or by intravenous infusion. The review found that bisphosphonates may reduce pain intensity in the short-term (around one to three months after treatment), but immediate-, medium-, and long-term effects were unclear.

The data suggest that bisphosphonates probably increase the risk for adverse events, including joint and muscle, though serious harms were rare. The researchers noted considerable variability in results across studies that could not be fully explained. Some findings hinted that patients with greater underlying bone metabolism changes—one theorized driver of CRPS in its early stages—may respond more favorably, but current evidence is insufficient to confirm this.

Overall, the authors say that while bisphosphonates may offer short-term pain relief for CRPS, clinicians should weigh potential benefits against adverse effects and the lack of long-term efficacy data. They add that more research is needed to identify who is most likely to benefit and to determine optimal dosing and treatment duration.

More information Michael C. Ferraro et al, Efficacy and Safety of Bisphosphonates for Complex Regional Pain Syndrome, Annals of Internal Medicine (2025). DOI: 10.7326/annals-25-03693 Journal information: Annals of Internal Medicine