Effect of Methylprednisolone or Zoledronic Acid on Resolution of Active Charcot Neuroarthropathy in Diabetes: A Randomized, Double-Blind, Placebo-Controlled Study

Charcot neuroarthropathy (CN) is a complex syndrome affecting people with diabetes and peripheral neuropathy but preserved vascularity. Without early intervention, active CN may have long-term consequences (1). Recent studies suggest the role of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in mediating inflammatory osteolysis by activating the receptor activator of nuclear factor-κB (RANKL-NF-κB) pathway, thus perpetuating bone loss in an insensate foot with active CN (2,3). The goal of treatment in active CN is therefore to curtail the ongoing inflammation and/or osteolysis. Antiresorptive agents to inhibit osteolysis have been used with modest success (4,5), but anti-inflammatory agents have not been evaluated for CN. We studied the efficacy of methylprednisolone (MP) or zoledronic acid (ZA) in comparison with placebo in active CN along with total contact cast (TCC) as the primary modality. Included participants had a clinical diagnosis of active CN (erythematous and swollen) with a foot temperature difference exceeding 2°C by infrared dermal thermometry (FLIR Systems, Inc., Orlando, FL) compared with a similar site on the opposite foot, substantiated by X-ray and/or MRI. Bone turnover markers (BTMs) P1NP and CTX (Elecsys; Roche Diagnostics, Mannheim, Germany) were estimated by electrochemiluminescence …