{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:52:59Z","timestamp":1791402779036,"version":"4.3.3"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nAims<\/jats:title>\nInflammatory 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.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nForty-three patients with active CN (temperature difference >2\u00b0C 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.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nThirty-six participants (24 male, 12 female) were randomized (11 in group A, 12 group B, 13 group C). The mean age was 57.7\u00b1 9.9 years, duration of diabetes 12.3\u00b1 5.8 years and symptom duration 6.5\u00b1 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 \u00b1 0.89 years of follow-up.<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nBisphosphonate 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.<\/jats:p>\n<\/jats:sec>\n\nTrial registration<\/jats:title>\nClinicalTrials.gov:<\/jats:bold> NCT03289338<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0259224","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T18:34:54Z","timestamp":1636396494000},"page":"e0259224","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Long-term foot outcomes following differential abatement of inflammation and osteoclastogenesis for active Charcot neuroarthropathy in diabetes mellitus"],"prefix":"10.1371","volume":"16","author":[{"given":"Liza","family":"Das","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-3102","authenticated-orcid":true,"given":"Ashu","family":"Rastogi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Jude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Prakash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Bhansali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"pone.0259224.ref001","first-page":"161","article-title":"Sur quelques arthropathies qui paraiise d \u0301ependre d\u2019 une l \u0301esion du cerveauou de la mouelle \u0301epini`ere","volume":"1","author":"JM Charcot","year":"1868","journal-title":"Arch Physiol Norm Pathol"},{"issue":"6","key":"pone.0259224.ref002","first-page":"361","article-title":"Charcot foot in diabetes: farewell to the neurotrophic theory","volume":"38","author":"E Chantelau","year":"2006","journal-title":"HormMetab Res"},{"issue":"9","key":"pone.0259224.ref003","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1007\/s00125-004-1477-5","article-title":"Vascular calcification and osteolysis in diabetic neuropathy\u2014is RANK-L the missing link?","volume":"47","author":"W. 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