Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial

Jude, Edward B.; Selby, Peter L.; Burgess, J Hay; Lilleystone, P.; Mawer, E. B.; Page, Sean; Donohoe, Mollie; Foster, Alethea Vm; Edmonds, Michael; Boulton, Andrew J.M.

doi:10.1007/s001250100008

Cited by 268 publications

(153 citation statements)

References 14 publications

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“…The median time to resolution in this survey was longer than that reported in single-centre cohorts [11][12][13][14], one possible explanation being that we had predefined resolution as the patient being ambulant in normal or orthotic footwear. As the measuring, ordering, manufacture, fitting and 'breaking-in' of such footwear can take several weeks, it is possible that the actual time to resolution was rather shorter than reported here.…”

Section: Discussionmentioning

confidence: 63%

Audit of acute Charcot’s disease in the UK: the CDUK study

et al. 2011

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Aims/hypothesis We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p=0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p=0.005). Conclusions/interpretation The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial.

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Section: Discussionmentioning

confidence: 63%

Audit of acute Charcot’s disease in the UK: the CDUK study

et al. 2011

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“…In this pilot study, the first to address the underlying disease process, symptoms improved and there was normalisation of the skin temperature differential between acute and non-involved feet, as well as a fall in bone turnover, as judged by alkaline phosphatase [72]. These observations resulted in a randomised, double-blind trial of intravenous Pamidronate versus placebo in acute CN [75]. The confirmation by…”

Section: Charcot Neuroarthropathymentioning

confidence: 81%

The diabetic foot: from art to science. The 18th Camillo Golgi lecture

2004

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Diabetic foot ulceration represents a major medical, social and economic problem all over the world. While more than 5% of diabetic patients have a history of foot ulceration, the cumulative lifetime incidence may be as high as 15%. Ethnic differences exist in both ulcer and amputation incidences, with both being less common in patients of Indian subcontinent origin living in the UK. Foot ulceration results from the interaction of several contributory factors, the most important of which is neuropathy. With respect to the management of acute Charcot neuroarthropathy in diabetes, recent studies suggest that bisphosphonates reduce disease activity as judged not only by differences in skin temperature, but also by assessing markers of bone turnover. The use of the total-contact cast is demonstrated in the treatment of acute Charcot feet and of plantar neuropathic ulcers. Histological evidence suggests that pressure relief results in chronic foot ulcers changing their morphological appearance by displaying some features of an acute wound. Thus, repetitive stresses on the insensate foot appear to play a major role in maintaining ulcer chronicity. It is hoped that increasing research activity in foot disease will ultimately result in fewer ulcers and less amputation in diabetes.

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“…Its dependence on increased blood flow explains why the process responds to rest (which will help to reduce it) and, possibly, to bisphosphonates [37,38]. Bisphosphonates inhibit the action of osteoclasts, although not by impacting directly on the OPG/RANK-L system [39,40], but their use also reduces local blood flow in other conditions associated with regional hyperaemia [41,42].…”

Section: Opg/rank-l In Charcot Footmentioning

confidence: 99%

Vascular calcification and osteolysis in diabetic neuropathy?is RANK-L the missing link?

Jeffcoate

2004

Diabetologia

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Diabetic neuropathy is associated with osteopenia and calcification of vascular smooth muscle cells. These changes are most marked in patients with acute neuropathic osteoarthropathy (Charcot foot), in which osteopenia is universal and the prevalence of vascular calcification exceeds 90%. While it has been thought that both osteopenia and vascular calcification may be linked to sympathetic denervation with increased peripheral limb perfusion, the cellular mechanism was not clear. However, the recent recognition that the receptor activator of nuclear factor kappa B ligand (RANK-L)/osteoprotegerin (OPG) signalling pathway is central to the processes regulating bone turnover in a wide variety of medical conditions has raised the possibility that the same cytokines may be involved in the osteolysis which accompanies diabetic neuropathy. This is made more likely by the realisation that the RANK-L/OPG pathway is also thought to mediate the calcification of vascular smooth muscle cells in coronary and peripheral vascular disease. The circumstantial evidence underpinning this hypothesis is reviewed here, and it is suggested that the unregulated activation of RANK-L-mediated effects on bone and arteries may be triggered by the loss of nerve-derived peptides, e.g. calcitonin gene-related peptide, which normally exert a moderating influence on the pathway. Keywords

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Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial

Cited by 268 publications

References 14 publications

Audit of acute Charcot’s disease in the UK: the CDUK study

Audit of acute Charcot’s disease in the UK: the CDUK study

The diabetic foot: from art to science. The 18th Camillo Golgi lecture

Vascular calcification and osteolysis in diabetic neuropathy?is RANK-L the missing link?

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