SLR - August 2020 - Amreet Kaur

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

Reference: Das L, Bhansali A, Prakash M, Jude EB, Rastogi A. Effect of Methylprednisolone or Zoledronic Acid On Resolution of Active Charcot Neuroarthropathy in Diabetes: A Randomized, Double-Blind, Placebo-Controlled Study. Diabetes Care. 2019 Sept 08; 42, 185-186. 

Scientific Literature Review

Reviewed By: Amreet Kaur, DPM 
Residency Program: VA Puget Sound Health Care System - Seattle WA 

Podiatric Relevance: Evaluating medicinal treatments for active CN foot in conjunction with TCC.

Methods: A randomized double-blind, placebo-controlled study was performed on 36 patients experiencing active CN. Active CN was determined according to clinical findings of erythema and edema and a measured foot temperature exceeding 2 degrees Celsius compared to a similar site on the contralateral foot. Additionally, imagery (X-RAY, MRI), bone turnover markers (P1NP and CTX), and inflammatory markers (TNF-a and IL-1B) were also evaluated. The patients were then divided into three groups: Group A used methylprednisolone (MP), group B used zoledronic acid (ZA), and group C was the placebo and used normal saline (NS). Each group received onedose of their treatment each month for three months. Every two weeks patients were evaluated with, on average, three temperature recordings 30 minutes after TCC removal. Primary outcome was remission, which was defined as <2 degrees Celsius difference in skin temperature during two consecutive clinic visits. Secondary outcomes were the aforementioned lab markers which were obtained at initiation and at the six-month mark of the study. 

Results: There was no statistical difference in time to remission time between the ZA (14.6 +/- 4.4 Weeks) and placebo groups (13.5 +/- 2.9 weeks) but the remission time of the MP group was significantly higher (15.5 +/- 4.2 Weeks). In addition, the ZA and placebo groups had a similar reduction in cytokines (TNFa and IL-1b). ZA and placebo both had a decrease in bone turnover markers (CTX and P1NP), specifically a 35 percent and 24 percent reduction in the ZA group compared to 11 percent and 19 percent reduction in the placebo group. Interestingly, the MP group showed mixed results in regards to the bone turnover markers where an 18 percent increase in CTX and a 5 percent decrease in P1NP was noted. There also was a 27 percent and 30 percent reduction in the inflammatory markers TNFa and IL-1b respectively.

Conclusions: There was no statistical benefit for the use of MP or ZA in conjunction with TCC in active Charcot patients when compared with TCC alone (Placebo), with MP being least beneficial. Furthermore, MP had an increase in bone turnover markers and a reduction in cytokines, but these findings did not seem to prove efficacy of MP as this group experienced the longest resolution time. Consequently, the reduction in cytokines had little impact on the independent RANKL pathway role on osteolysis. MP influences the RANKL pathway by down-regulating CGRP and osteoprotergerin, both markers which antagonize the RANKL pathway which helps to explain the increase in bone turnover markers and prolonged remission time. This study was limited due to patient size although it did have thorough follow-up monitoring. Further analysis with prolonged study time and patient size would be beneficial.

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