Ann Intern Med

Bisphosphonates for complex regional pain syndrome: Short term relief but limited long term payoff

December 24, 2025

A systematic review and meta-analysis of 11 randomized trials (N = 754) found that bisphosphonates may reduce pain intensity in the short term (>4 weeks to 3 months) for complex regional pain syndrome (CRPS), with a mean difference of -10.0 points on a 0-100 scale. However, bisphosphonates probably increase adverse events and showed little to no difference in pain at immediate (≤4 weeks) or medium-term (>3-6 months) timepoints. The evidence was predominantly from CRPS type I patients and included non-U.S.-approved formulations like neridronate and clodronate.

Clinical takeaway: Consider bisphosphonates for early CRPS (particularly <4 months duration), but counsel patients about limited durability of benefit and expect adverse events including GI intolerance, polyarthralgia, and fever.

Source:

Ferraro MC, et al. (2025, December 16). Ann Intern Med. Efficacy and Safety of Bisphosphonates for Complex Regional Pain Syndrome : A Systematic Review and Meta-analysis. https://pubmed.ncbi.nlm.nih.gov/41397259/