Efficacy and Safety of Bisphosphonates Explored in Complex Regional Pain Syndrome

THURSDAY, Dec. 18, 2025 (HealthDay News) — Bisphosphonates may reduce complex regional pain syndrome (CRPS) pain intensity in the short term, according to a study published online Dec. 16 in Annals of Internal Medicine.

Michael C. Ferraro, from the University of New South Wales in Sydney, and colleagues conducted a systemic review and meta-analysis to examine the efficacy and safety of bisphosphonates versus placebo for CRPS. Eleven trials with 754 participants, assessing alendronate, clodronate, neridronate, pamidronate, and zoledronate, were included.

The researchers found with low certainty that in the immediate term (four weeks or less) bisphosphonates may result in little to no difference in pain intensity (mean difference [MD], −9.1 [95 percent confidence interval, −19.2 to 1.1]), while they may reduce pain intensity in the short term (more than four weeks to three months; MD, −10.0 [−18.9 to −1.1]), and result in little to no difference in pain intensity in the medium term (more than three months to six months; MD, 8.0 [−15.4 to 31.4]). Regarding the effects of bisphosphonates on pain intensity in the long term (more than six months), the evidence was very uncertain (MD, −2.5 [−19.6 to 14.6]). Bisphosphonates probably increase risk for adverse events (risk ratio, 1.1 [1.0 to 1.2]; moderate certainty).

“While this review represents the best evidence to date on treatment of CRPS, unexplained heterogeneity and limited medium- or long-term data restrict clinical application,” the authors write.

Several authors disclosed financial ties to the biopharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)