Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study

Rheumatology (Oxford). 2013 Mar;52(3):534-42. doi: 10.1093/rheumatology/kes312. Epub 2012 Nov 30.


Objective: Complex regional pain syndrome type I (CRPS-I) is a severely disabling pain syndrome for which no definite treatment has been established. The aim of this multi-centre, randomized, double-blind placebo-controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I.

Methods: Eighty-two patients with CRP-I at either hand or foot were randomly assigned to i.v. infusion of 100 mg neridronate given four times over 10 days or placebo. After 50 days the former placebo patients were given open label the same regimen of neridronate.

Results: Within the first 20 days, visual analogue scale (VAS) score decreased significantly more in the neridronate group. In the following 20 days, VAS remained unchanged in the placebo group and further decreased in the active group by 46.5 mm (95% CI -52.5, -40.5) vs 22.6 mm (95% CI -28.8, -16.3) for placebo group (P < 0.0001). Significant improvements vs placebo were observed also for a number of other indices of pain and quality of life. During the open-extension phase in the formerly placebo group the results of treatment were superimposable on those seen during the blind phase in the active group. A year later none of the patients was referring symptoms linked to CRPS-I.

Conclusion: In patients with acute CRPS-I, four i.v. infusions of neridronate 100 mg are associated with clinically relevant and persistent benefits. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice for CRPS-I.

Trial registration: EU Clinical Trials Register,, 2007-003372-18.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / therapeutic use*
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pain Measurement
  • Reflex Sympathetic Dystrophy / drug therapy*
  • Treatment Outcome


  • Bone Density Conservation Agents
  • Diphosphonates
  • 6-amino-1-hydroxyhexane-1,1-diphosphonate