Complex Regional Pain Syndrome type I (CRPS-I), in the past called reflex dystrophy, is a disabling disorder affecting a peripheral limb, usually developing after a trauma to an extremity. Several different diagnostic criteria have been proposed, and recently updated “Budapest Criteria” have been widely accepted, to diagnose CRPS-I. The diagnosis is made using clinical criteria and is based on the sole clinical history and examination. CRPS-I is characterized by the presence of spontaneous or stimulus-induced pain, disproportionate to the inciting event, allodynia and hyperalgesia. These symptoms are associated to a wide variety of autonomic and motor disturbances, or trophic abnormalities. There are no specific laboratory or radiological diagnostic procedures for CRPS-I, but a variety of tests may be useful to exclude other clinical conditions. These include x-rays, three-phase bone scintigraphy and MRI.
At present, several pharmacological treatments (e.g., analgesics, anesthetics, anticonvulsants, antidepressants, oral muscle relaxants, corticosteroids, calcitonin, bisphosphonates, and calcium channel blockers) have been proposed to reduce pain and pain sensitization, and to improve functional status in patients presenting with CRPS-I. While most of these medications demonstrated poor or partial efficacy on the short-term, bisphosphonates (BPs) showed better long-term beneficial effects on pain reduction and functional recovery.
BPs are potent inhibitors of osteoclastic activity widely used for the management of osteoporosis and other metabolic bone diseases. Their primary pharmacological action is the reduction of bone turnover. An enhanced osteoclastic activity has never been clearly demonstrated in CRPS-I. Therefore, it is likely that the positive effects of BPs in this condition are not related to their anti-resorptive properties, but to a more complex interaction between these pharmacological agents and the pathophysiological mechanisms underlying CRPS-I.
Results of several clinical trials have suggested the potential beneficial effects of BPs in CRPS-I. In five randomized-controlled trials, oral and intravenous alendronate, and intravenous clodronate, pamidronate and neridronate demonstrated to be effective in reducing pain and improving physical function in patients presenting with CRPS-I, with a good profile of safety and tolerability. Although these trials have a number of limitations, including the small samples enrolled, there is sufficient evidence to support the use of BPs as agents of choice in the management of CRPS-I.
Disclosure of Interest A. Giusti Consultant for: Chiesi, Dynamicom, Eli Lilly, Abiogen, Speakers bureau: Merck & Co., AMGEN, Eli Lilly, Chiesi, Abiogen