Complex regional pain syndrome type I (CRPS-I) is a common and disabling disorder affecting a peripheral limb, usually developing after a trauma to an extremity. CRPS-I is characterized by presence of spontaneous pain, allodynia and hyperalgesia, disproportionate to the inciting event and by a variety of autonomic disturbances and trophic abnormalities. The pathophysiology of CRPS-I has not been fully understood. Experimental models have suggested a sort of neurogenic inflammation occurs after a traumatic event. Early in the disease there is documented low oxygen to the tissues and bone with later sympathetic nervous system activation. Bisphosphonates (BPs) are potent inhibitors of osteoclastic activity widely used for the management of osteoporosis and other metabolic bone diseases. Their primary action is the reduction of bone turnover. Since an enhanced osteoclastic activity has never been clearly demonstrated in CRPS-I, it is likely that the positive effects of BPs in this condition are not related to their antiresorptive properties, but to a more complex interaction between these pharmacological agents and the pathophysiological mechanisms underlying CRPS-I. Essentially, we don’t know how they work. 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. Please ask one of our Balcones Pain Consultants’ Physicians about this off label infusion treatment for CRPS and if it is right for you.