Intravenous Pamidronate in Persistent Complex Regional Pain Syndrome (CRPS): A Retrospective Observational Study on Effectiveness and Tolerability

Purpose: Pamidronate is a nitrogen-containing bisphosphonate with immunomodulatory and anti-osteoclastic properties that has shown benefit in early-onset complex regional pain syndrome (CRPS), yet evidence in persistent CRPS remains limited. Given that chronicity may attenuate therapeutic response, this study evaluates the effectiveness and tolerability of intravenous pamidronate in CRPS patients managed in routine clinical practice. Patients and Methods: We conducted a single-center retrospective observational study, including all adult CRPS patients treated with pamidronate between 2014 and 2024 at our tertiary referral center. Data were collected from medical records at baseline, during treatment and at routine follow-up at approximately 1-, 3-, 6-, and 12-months post-treatment. The primary outcome was the pain trajectory, analyzed using a linear mixed-effects model. Responders were defined by a ≥ 2-point NRS reduction or subjective benefit when NRS data were unavailable. Results: Of 110 eligible patients, 97 were included with a median age of 45 (IQR 32– 54), and a median disease duration of 31 months (IQR 9– 97). Baseline mean NRS was 7.95 (95% CI: 7.66 to 8.25), declining by 1.10 points (95% CI: − 1.49 to − 0.70; p< 0.001) at 1 month and by 0.66 points (95% CI: − 1.13 to − 0.20; p< 0.01) at 3 months. Responder rates were 34% and 22%, respectively. Treatment-related adverse events occurred in 91% of patients but led to discontinuation in only 6%. Conclusion: In patients with predominantly persistent CRPS, intravenous pamidronate was well tolerated and associated with a modest, short-term pain relief up to 3 months. No sustained analgesic benefit was evident at later timepoints. Keywords: complex regional pain syndrome, pamidronate, interventional pain management, chronic pain, treatment outcome, drug-related side effects and adverse reactions