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

Rastogi, Ashu; Bhansali, Anil; Jude, Edward B.

doi:10.1007/s00592-020-01664-9

Cited by 23 publications

(13 citation statements)

References 35 publications

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“…In fact, a recent meta-analysis of randomized controlled trials of all the studied medical therapies for active CN found no difference in outcomes in comparison to struct o oading with TCC. [30] Periodic analysis of bone turnover markers (P1NP and CTX) suggested maximum osteolysis at baseline in all groups, in accordance with clinical activity of active CN as demonstrated previously. [21] Both P1NP and CTX declined in the zoledronate and placebo groups on follow-up without any signi cant difference between the groups, suggesting an overall decrease in bone turnover because of off-loading.…”

Section: Discussionsupporting

confidence: 88%

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Differential Abatement of Inflammation And Osteoclastogenesis In Active Charcot Neuroarthropathy: Mechanistic Insights From Randomized Controlled Study

Das¹,

Rastogi²,

Prakash³

et al. 2021

Preprint

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AimsInflammatory osteolysis is the sine-qua-non of active Charcot neuroarthropathy (CN). This study is aimed to provide mechanistic insights into pathogenesis of CN by exploring the role of methylprednisolone or zoledronate for remission of active CN. MethodsThirty-six patients with active CN (temperature difference >2°C from normal foot) were evaluated for time to remission. Patients were off-loaded with total contact cast and randomised to receive either methylprednisolone (1gm), zoledronate (5mg) or placebo (100ml normal saline) once monthly infusion for three consecutive months. Change in inflammatory cytokines (TNF-α, IL-1β), bone turnover markers (P1NPand CTX) and bone mineral content (BMC) was assessed. ResultsTime to remission of active CN was 19.4 ± 2.8 weeks with methylprednisolone compared to14.6 ± 4.4 and 13.5 ± 2.9 weeks (p<0.05) with zoledronate and placebo, respectively. TNF-α levels reduced by 27% (p=0.03) with methylprednisolone,18% with zoledronate and 16% with placebo (p>0.05), while IL-1β reduced by 30% (p=0.02) with methylprednisolone, 21% with zoledronate and 16% with placebo (p>0.05). P1NP decreased by 5%, 24% and 19% with methylprednisolone, zoledronate and placebo, respectively. CTX decreased by 35% and 11% with zoledronate and placebo respectively but increased with methylprednisolone (18%) (p>0.05). Conclusion Effective suppression of either inflammation with methylprednisolone or osteoclastogenesis with zoledronate do not translate into earlier remission of active CN. The role of non-cytokine and non-inflammatory pathways for the activation of osteoclastogenesis in CN is purported.

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Section: Discussionsupporting

confidence: 88%

“…Among adverse events, u-like reaction (n = 5, 41.6%) and acute kidney injury (de ned as increase in serum creatinine > 0.5mg/dl above baseline or estimated GFR under 30ml/min/m 2 ) (n = 2, 16.6%) were the common adverse events noted with the use of zoledronate [30]. Worsening of glycemic pro le was observed with methylprednisolone.…”

Section: Resultsmentioning

confidence: 99%

Differential Abatement of Inflammation And Osteoclastogenesis In Active Charcot Neuroarthropathy: Mechanistic Insights From Randomized Controlled Study

Das¹,

Rastogi²,

Prakash³

et al. 2021

Preprint

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“…Initial studies with alendronate and pamidronate showed gain in terms of improvement in symptom score and suppression of bone turnover but their effect on clinical remission was either not found to be significant or not investigated. Systematic reviews [ 28 , 43 ] and few recent studies suggested that bisphosphonates may not reduce time to remission in patients with active CN or may even increase the time in cast [ 16 , 19 ]. The current study shows a remarkable decrease in bone resorption markers and consequent increase in BMC with ZL suggesting effective suppression of ongoing osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…We observed no difference in remission rates for active CN with zoledronate compared to placebo and increased duration to remission with steroids [ 23 ]. A recent systematic review also confirmed no added benefit of pharmacological agents for short term outcome defined as remission of active CN [ 28 ]. However, long term consequences of CN are pertinent clinical outcomes including the occurrence of deformities, fractures, amputations and mortality [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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

Das¹,

Rastogi²,

Jude³

et al. 2021

PLoS ONE

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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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“… 47 This was confirmed in a recent systematic review. 57 The poor quality of the evidence and inconsistency in findings have led to UK guidelines and international consensus documents, and a recent systematic review not recommending the use of pharmacological therapies to treat CN, unless being evaluated in a clinical trial. 24 , 57 , 58 Further research is needed to examine and evaluate the effectiveness of pharmacological therapies in treating CN.…”

Section: Treatment Of Cnmentioning

confidence: 99%

Controversies in the management of active Charcot neuroarthropathy

Gooday

Hardeman

Poland

et al. 2023

Therapeutic Advances in Endocrinology

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Charcot neuroarthropathy (CN) was first described over 150 years ago. Despite this there remains uncertanity around the factors that contribute to its development, and progression. This article will discuss the current controversies around the pathogenesis, epidemiology, diagnosis, assessment and management of the condition. The exact pathogenesis of CN is not fully understood, and it is likely to be multifactorial, with perhaps currently unknown mechanisms contributing to its development. Further studies are needed to examine opportunities to help screen for and diagnose CN. As a result of many of these factors, the true prevalence of CN is still largely unknown. Almost all of the recommendations for the assessment and treatment of CN are based on low-quality level III and IV evidence. Despite recommendations to offer people with CN nonremovable devices, currently only 40–50% people are treated with this type of device. Evidence is also lacking about the optimal duration of treatment; reported outcomes range from 3 months to more than a year. The reason for this variation is not entirely clear. A lack of standardised definitions for diagnosis, remission and relapse, heterogeneity of populations, different management approaches, monitoring techniques with unknown diagnostic precision and variation in follow-up times prevent meaningful comparison of outcome data. If people can be better supported to manage the emotional and physical consequences of CN, then this could improve people’s quality of life and well-being. Finally, we highlight the need for an internationally coordinated approach to research in CN.

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

Cited by 23 publications

References 35 publications

Differential Abatement of Inflammation And Osteoclastogenesis In Active Charcot Neuroarthropathy: Mechanistic Insights From Randomized Controlled Study

Differential Abatement of Inflammation And Osteoclastogenesis In Active Charcot Neuroarthropathy: Mechanistic Insights From Randomized Controlled Study

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

Controversies in the management of active Charcot neuroarthropathy

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