Efficacy of medical treatment for Charcot neuroarthropathy: a systematic review and meta-analysis of randomized controlled trials

No pharmacotherapeutic agents are yet recommended for active CN though many anti-resorptive agents have been studied. We conducted a systematic review and meta-analysis of the randomized placebo-controlled trials (RCTs) evaluating the time to remission of active CN with anti-resorptive or antiinflammatory drugs. RCTs published in PubMed, EMBASE, SCOPUS and Cochrane Library from January 1994 to December 2019 were accessed. We reviewed studies and extracted information on study design, participants' characteristics, time to remission, bone turnover markers, bone mineral content (BMC) and temperature difference between feet. Five RCTs out of 588 total identified records were included. Standardized mean differences (SMD) between groups with 95% CI are summarized. Pharmacotherapy nonsignificantly increased time to remission [SMD 0.52 weeks (- 0.71, 1.75), p = 0.402; I2 = 88.6%] as compared to TCC alone. The pooled median time to remission with the intervention was 18.5 weeks (11.2, 28.1) compared to 16.8 weeks (8.7, 27.7) with TCC. A nonsignificant increase in BMC [SMD 3.39% (- 0.78, 7.56), p = 0.109; I2 = 96.7%], a decrease in foot temperature [SMD - 0.42 degrees C (- 0.78, - 0.07), p = 0.020; I2 = 0%] and alkaline phosphatase [SMD = -2.51% (- 3.24, - 1.77), p < 0.001; I2 = 0%] was observed with intervention. Limited evidence from available studies does not support the role of anti-resorptive or anti-inflammatory drugs for earlier remission when added to offloading with total contact cast for active CN of the foot.