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Complex regional pain syndrome (CRPS) type I, also known as reflex sympathetic dystrophy, usually develops after trauma or immobilization, is characterized by focal pain and autonomic dysregulation, and sometimes focal trophic changes such as osteoporosis. The pathophysiology is unknown and there have been few controlled treatment trials. The purpose of this study was to obtain pilot data on the safety and efficacy of a highly potent bisphosphonate, ibandronate, for the treatment of CRPS, which might be responsive to bisphosphonates' inhibition of osteoclast and anti-inflammatory activity.An open-label trial (n=10) of 6 mg ibandronate infusions was administered on each of 3 days. The infusions were preceded by a 2-week baseline period, and followed by a 4-week follow-up period.One participant dropped out after the first infusion because of a decreased glomerular filtration rate. Otherwise, aside from transitory flu-like symptoms characteristic of bisphosphonate treatments, the drug was well tolerated. Significant postintervention improvements were observed in average and worst pain ratings; the neuropathic pain qualities of “unpleasant,” “sensitive,” “deep,” “intense,” “surface,” “hot,” “cold,” “sharp,” and “dull”; and hyperalgesia and allodynia. Participants with hand CRPS improved significantly more than those with foot CRPS in average and worst pain, as well as in the following neuropathic pain qualities: “dull,” “intense,” “deep,” and “time.”These data justify a randomized, double-blind, placebo-controlled trial of ibandronate that should perhaps be limited to patients with hand CRPS.