Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study

Objective. To evaluate the efficacy of intravenous (iv) clodronate in patie nts with reflex sympathetic dystrophy syndrome (RSDS) and to assess the uri nary excretion of type I collagen crosslinked N-telopeptide (NTx) before an d after the treatment. Methods. Thirty-two patients with RSDS were randomized to receive either iv clodronate 300 mg daily for 10 consecutive days or placebo. Forty days lat er, the placebo treated patients received the clodronate treatment. Outcome measures included as a primary endpoint the visual analog scale of pain (V AS, range 0-100); secondary endpoints were a clinical global assessment (CG A, range 0-3) and an efficacy verbal score (EVS, range 0-3). Clinical and b iochemical assessments were performed before the treatment, 40 (T40), 90 (T 90), and 180 (T180) days later. Results. At T40 the 15 patients randomized to clodronate treatment showed s ignificant decreases of VAS and CGA (p = 0.002, p = 0.001, respectively). C ompared with the placebo group (17 patients), significant differences were found in all clinical variables (VAS: p = 0.001; CGA: p = 0.001; EVS: p < 0 .0001). A further. clinical improvement was observed throughout the study. Pooling the results of all 32 patients after clodronate treatment, at T180 the overall percentage decrease of VAS was 93.2 +/- 15.6%, with 30 patients significantly improved or asymptomatic. Significant inverse correlations b etween baseline NTx values and decreases of VAS were found at T90 (p = 0.03 ) and T180 (p = 0.01). No adverse events related to treatment occurred. Conclusion. A 10 day iv clodronate course is better than placebo and effect ive in the treatment of RSDS. NTx seems to be a predictive factor for clodr onate efficacy.