Biphosphonates for the therapy of complex regional pain syndrome I – Systematic review

Abstract

Objectives: Several studies found that biphosphonates counteract locally increased bone resorption and associated pain in patients with complex regional pain syndrome I (CRPS I). We performed a systematic review of all randomised controlled trials to assess the benefit of biphosphonates in the treatment of CRPS I patients with bone loss. Data sources: We searched Medline, Embase (April 2007) and the Cochrane Library and screened bliographies of included studies. Review methods: We selected randomised trials comparing biphosphonates with placebo, with the goal of improving pain, function and quality of life in patients with CRPS I. Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, conflicts were resolved with discussion and/or trial authors were contacted for further details. We calculated the study size weighted pooled mean reduction of pain intensity (measured with a visual analogue scale (VAS)). Results: Four trials of moderate quality fulfilled our inclusion criteria. In respect to function and quality of life there was a trend in favour of biphosphonates but differences in outcome assessment impeded pooling of results. Two trials provided sufficient data to pool pain outcomes. Biphosphonates reduced pain intensity by 22.4 and 21.6mm on a VAS after 4 and 12 weeks of follow‐up. Data on adverse effects were scarce. Conclusions: The very limited data reviewed showed that bisphosphonates have the potential to reduce pain associated with bone loss in patients with CRPS I. However, at present there is not sufficient evidence to recommend their use in practice.

Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain

“…7 B and C), both of which are in widespread clinical use. Some bisphosphonates attenuate the neuropathic pain associated with complex regional pain syndrome 1 in conditions involving bone abnormalities (16). In the present study, bisphosphonate compounds other than clodronate exerted weak or no analgesic effects, similar to their inhibitory effects on VNUT, suggesting that the analgesic effect of other bisphosphonates depends on the inhibition of bone resorption (Fig.…”

“…Although they are used to treat bone diseases accompanied by chronic neuropathic or inflammatory pain (16)(17)(18), the mechanism underlying this analgesic effect is unknown. Notably, non-nitrogen-containing bisphosphonates (first generation) result in less inhibition of bone resorption but have fewer side effects than nitrogen-containing bisphosphonates (second and third generations) (19)(20)(21) (Fig.…”

Neridronate: From Experimental Data to Clinical Use

“…Nevertheless, various BPs have shown evidence of effectiveness in controlling pain and functional symptoms and in reducing and preventing focal bone loss in randomized controlled trials with limited sample sizes. [34][35][36][37] Neridronate has also been evaluated as a treatment for CRPS-I in a recent large multicentre, randomized, double-blind, placebo-controlled trial. About 82 patients with CRPS-I in either their hand or foot were randomly assigned to receive either an intravenous infusion of 100 mg of neridronate every 3 days for a total of 4 times or the placebo.…”

“…Neridronate is officially approved in Italy as a treatment for OI, [17][18][19][20][21][22][23][24][25][26][27][28] Paget's disease of bone, [29][30][31][32][33] and CRPS-I, [34][35][36][37][38] but various evidence suggests its potential effectiveness as a treatment for other bone diseases as well.…”

Komplexes regionales Schmerzsyndrom

“…In insgesamt 4 kontrollierten, randomisierten Studien wurde eine gewisse Wirksamkeit von Bisphosphonaten auf die Schmerzhaftigkeit, Schwellung und Beweglichkeit bei CRPS belegt [67]. Die Wirkung ist eher auf die akute Phase mit Inflammation beschränkt.…”