Complex regional pain syndrome is a condition that is not well understood.  It is characterized by spontaneous pain, pain with very light tough, prolonged pain and pain out of proportion to original injury.  It causes skin, hair, nail, and bone changes.  Bisphosphonates are a class of medication that inhibit the cells that re-absorb bone which is the cause of osteoporosis.  Inhibiting osteoclasts should not theoretically be beneficially in complex regional pain syndrome but several trials show that this class of medication is helpful.  Both oral and intravenous alendronate and intravenous clodronate, pamidronate and neridronate demonstrated efficacy in reducing pain and improving function in patients with complex regional pain syndrome with a good safety profile and tolerability.  According the authors, there is sufficient evidence to support use of the drug class, bisphosphonates in the management of complex regional pain syndrome.

The Research

Treatment of Complex Regional Pain Syndrome Type I with Bisphosphonates

RMD Open. 2015 Aug 15;1(Suppl 1):e000056. doi: 10.1136/rmdopen-2015-000056. eCollection 2015.

Giusti A¹, Bianchi G².

Author information

• ¹Bone Clinic, Department of Gerontology and Musculoskeletal Sciences , Galliera Hospital , Genoa , Italy.
• ²Department of Locomotor System, Division of Rheumatology , ASL3 , Genova , Italy.

Abstract

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 characterised 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 that an initial triggering event may produce the release of proinflammatory neuropeptides and cytokines, generating a sort of neurogenic inflammation. Thereafter, increased microvascular permeability and intramedullary pressure, reduced oxygen extraction and cellular hypoxia maintain and make the disease worse, producing metabolic tissue acidosis. In this context, it is probable that, far from being a key player, the sympathetic nervous system contributes interacting with these mechanisms and producing vasomotor disturbances. Bisphosphonates (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 antiresorptive 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 randomised 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.