Patchy Osteoporosis in Complex Regional Pain Syndrome

Abstract

Complex regional pain syndrome (CRPS), formerly known as “reflex sympathetic dystrophy” and “causalgia”, is a syndrome that refers to a chronic pain condition associated with autonomic disturbances of vasomotor and sudomotor origin (Birklein et al., 1998), along with trophic skin changes and patchy demineralization of the bones (Poplawski et al., 1983). CRPS is classified into type I and II; the former can develop after minor or remote trauma like stroke, spinal cord injury or myocardial infarction (Wasner et al., 1998); the latter can develop after a large peripheral nerve lesion (Janig & Baron, 2003). The syndrome corresponding to what was formerly described as reflex sympathetic dystrophy is now termed as CRPS type I; causalgia is now termed as CRPS type II (Merseky & Bogduk, 1994). Although the mechanism of CRPS has not been elucidated yet, recent studies indicate that it is a complex disorder that involves both the central and peripheral nervous systems (Daemen et al., 1998; Huygen et al., 2001). CRPS pathogenesis is heterogeneous and complex, which makes its treatment challenging. Pharmacological therapies of CRPS include anti-inflammatory drugs, systemic corticosteroid (Kingery, 1997), antidepressants, opioid (Mackey & Feinberg, 2007), anticonvulsants, free-radical scavengers, vasodilatory medication (Perez et al., 2010) and even bisphosphonate agents (Adami et al., 1997; Manicourt et al., 2004; Robinson et al., 2004; Varenna et al., 2000). In addition, vitamin C is recommended to prevent the occurrence of CRPS type I after wrist fracture (Perez et al., 2010). However, there is yet no single pharmacological agent or treatment algorithm that can resolve all of its heterogenic features. The efficacy for most pharmacological agents remains largely empirical, with the exception of bisphosphonate agents, which are the only agents with proven efficacy for CRPS based on multiple controlled trials (Adami et al., 1997; Brunner et al., 2009; Mackey & Feinberg, 2007;, Manicourt et al., 2004, Robinson et al., 2004, Varenna et al., 2000). In order to understand how these bisphosphonate agents are useful in CRPS treatment, it is imperative to understand the pathogenesis of patchy osteoporosis in CRPS. This section will first review CRPS, then it will introduce the different experimental animal models. Finally this section will discuss the different treatment agents that have been studied for patchy osteoporosis.