Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A systematic literature review and meta-analysis of randomized controlled trials versus placebo

ObjectivesComplex Regional Pain Syndrome Type 1 is a severely disabling pain syndrome with no definite established treatment. We have performed a systematic literature review and meta-analysis of all randomized controlled trials to assess the benefit of bisphosphonates on pain and function in patients with Complex Regional Pain Syndrome Type 1.MethodsA systematic literature search was performed in the Medline, Embase and Cochrane databases. Two authors selected independently blinded randomized trials comparing bisphosphonates to placebo on short-term (J30 to J40) and medium term pain (M2-M3), safety and function in patients with CRPS 1. The methodological quality of the studies was analyzed. Data were aggregated using the method of the inverse of the variance.Results258 articles were identified. Four trials of moderate to good quality comprising 181 patients (90 in the bisphosphonate group and 91 in the placebo group) were included in this meta-analysis. Short-term pain Visual Analog Scale was significantly lower in the bisphosphonate group versus the placebo group (SMD = −2.6, 95%CI [−1.8, −3.4], P < 0.001), as well as the medium term Visual Analog Scale pain (SMD = −2.5, 95%CI [−1.4, −3.6], P < 0.001). There were more adverse events in the bisphosphonate group (35.5%) than in the placebo group (16.4%) with a relative risk of 2.1 (95%CI [1.3, 3.5], P = 0.004) and a number needed to harm of 4.6, (95%CI [2.4, 168.0]) but no serious side effects.ConclusionsOur results suggest that bisphosphonates reduce pain in patients with Complex Regional Pain Syndrome type 1. Other studies are needed to determine their effectiveness.