title: Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/, 2007-003372-18.
authors.affiliation: Rheumatology Unit, Ospedale G. Pini, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Varenna
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
authors.forename: Davide
authors.initials: D
authors.lastname: Gatti
authors.forename: Luca
authors.initials: L
authors.lastname: Idolazzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Zucchi
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Malavolta
authors.forename: Luigi
authors.initials: L
authors.lastname: Sinigaglia
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D012019:Reflex Sympathetic Dystrophy / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate