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Clinical Trial
. 2021 Nov 8;16(11):e0259224.
doi: 10.1371/journal.pone.0259224. eCollection 2021.

Long-term foot outcomes following differential abatement of inflammation and osteoclastogenesis for active Charcot neuroarthropathy in diabetes mellitus

Liza Das  1 , Ashu Rastogi  1 , Edward B Jude  2 , Mahesh Prakash  3 , Pinaki Dutta  1 , Anil Bhansali  1
Affiliations
Clinical Trial

Long-term foot outcomes following differential abatement of inflammation and osteoclastogenesis for active Charcot neuroarthropathy in diabetes mellitus

Liza Das et al. PLoS One. .

Abstract

Aims: Inflammatory osteolysis is sine-qua-non of active Charcot neuroarthropathy (CN) causing decreased foot bone mineral density (BMD) and fractures. We aimed to explore the effect of anti-inflammatory or anti-resorptive agents for effect on foot bone mineral content (BMC) and consequent long-term outcomes of foot deformities, fractures and amputation.

Methods: Forty-three patients with active CN (temperature difference >2°C from normal foot) were evaluated. Patients were off-loaded with total contact cast and randomized to receive either methylprednisolone (1gm) (group A), zoledronate (5mg) (group B) or placebo (100ml normal saline) (group C) once monthly infusion for three consecutive months. Change in foot BMC was assessed at 6 months or at remission and followed subsequently up to 4 years for the incidence of new-onset fracture, deformities, or CN recurrence.

Results: Thirty-six participants (24 male, 12 female) were randomized (11 in group A, 12 group B, 13 group C). The mean age was 57.7± 9.9 years, duration of diabetes 12.3± 5.8 years and symptom duration 6.5± 2.8 weeks. BMC increased by 36% with zoledronate (p = 0.02) but reduced by 13% with methylprednisolone (p = 0.03) and 9% (p = 0.09) with placebo at remission. There were no incident foot fractures, however, two patients sustained ulcers, and 3 had new-onset or worsening deformities and none required amputation during 3.36 ± 0.89 years of follow-up.

Conclusion: Bisphosphonate for active CN is associated with an increase in foot bone mineral content as compared to decrease with steroids or total contact cast but long-term outcomes of foot deformities, ulceration and amputation are similar.

Trial registration: ClinicalTrials.gov: NCT03289338.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Randomisation protocol as per the CONSORT guidelines (CN- Charcot’s Neuroarthropathy).
Fig 2
Fig 2. Kaplan-Meier curve for remission of active Charcot foot in the three groups.
Fig 3
Fig 3. Bone mineral content in study groups at randomization and after 6 months.
Group A- Methylprednisolone; Group B- Zoledronate; Group C- Placebo.
Fig 4
Fig 4. Integrated pathophysiology and interactions between various factors in persons with diabetes implicated for the causation of active Charcot neuroarthropathy and efficacy of various evaluated therapeutic agents.
AGE- Advanced glycation end products; RAGE- Receptor for advanced glycation end products; eNOS- Endothelial nitric oxide synthase; SOFAT- secreted osteoclastogenic factor of activated T cells; RANKL- Receptor activator of nuclear factor-кβ, OPG- Osteoprotegerin; CGRP- Calcitonin gene related peptide; Charcot’s neuroarthropathy (CN).
See this image and copyright information in PMC

References

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