BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Department of Diabetes Diabetic Foot Clinic King's College Hospital NHS Foundation Trust London UK

Department of Orthopaedic Surgery University of Texas Southwestern Medical Center Dallas Texas USA

Department of Radiology University of Texas Southwestern Medical Center Dallas Texas USA

Diabetes Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Division of Endocrinology MUMC CARIM and CAPHRI Institute Maastricht The Netherlands

Elsie Bertram Diabetes Centre Norfolk and Norwich University Hospitals NHS Foundation Trust Norfolk UK

Gustave Dron Hospital Tourcoing Univ Lille Lille France

Italian Hospital of Buenos Aires Buenos Aires Argentina

Program in Physical Therapy Washington University School of Medicine St Louis Missouri USA

Secretary International Association of Diabetic Foot Surgeons Mumbai India

The Division of Metabolism Endocrinology and Diabetes The University of Michigan Medical School Ann Arbor Michigan USA

Zobrazit více v PubMed

Strotman PK, Reif TJ, Pinzur MS. Charcot arthropathy of the foot and ankle. Foot Ankle Int. 2016;37(11):1255-1263. https://doi.org/10.1177/1071100716674434

Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A, Group KS. Prevalence of polyneuropathy in pre-diabetes and diabetes is associated with abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Surveys S2 and S3. Diabetes Care. 2008;31(3):464-469. https://doi.org/10.2337/dc07-1796

Mascarenhas JV, Jude EB. The Charcot foot as a complication of diabetic neuropathy. Curr Diab Rep. 2014;14(12):561. https://doi.org/10.1007/s11892-014-0561-6

Santos J. IDF Diabetes Report on Diabetes Foot-Related Complications; 2022.

Wukich DK, Sadoskas D, Vaudreuil NJ, Fourman M. Comparison of diabetic charcot patients with and without foot wounds. Foot Ankle Int. 2017;38(2):140-148. https://doi.org/10.1177/1071100716673985

Frykberg RG, Belczyk R. Epidemiology of the charcot foot. Clin Podiatr Med Surg. 2008;25(1):17-28. https://doi.org/10.1016/j.cpm.2007.10.001

Sohn MW, Stuck RM, Pinzur M, Lee TA, Budiman-Mak E. Lower-extremity amputation risk after charcot arthropathy and diabetic foot ulcer. Diabetes Care. 2010;33(1):98-100. https://doi.org/10.2337/dc09-1497

Mabilleau G, Petrova NL, Edmonds ME, Sabokbar A. Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand. Diabetologia. 2008;51(6):1035-1040. https://doi.org/10.1007/s00125-008-0992-1

Uccioli L, Sinistro A, Almerighi C, et al. Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot. Diabetes Care. 2010;33(2):350-355. https://doi.org/10.2337/dc09-1141

Wukich DK, Schaper NC, Gooday C, et al. Guidelines on the diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023). Diab Metab Res Rev. 2023. in press.

Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100. https://doi.org/10.1371/journal.pmed.1000100

Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1136/bmj.b2535

Eichenholtz S. Charcot Joints. Charles C. Thomas; 1966.

Shibata T, Tada K, Hashizume C. The results of arthrodesis of the ankle for leprotic neuroarthropathy. J Bone Joint Surg Am. 1990;72(5):749-756. https://doi.org/10.2106/00004623-199072050-00016

Rastogi A, Bhansali A, Jude EB. Efficacy of medical treatment for Charcot neuroarthropathy: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2021;58(6):687-696. https://doi.org/10.1007/s00592-020-01664-9

Gooday C, Gray K, Game F, Woodburn J, Poland F, Hardeman W. Systematic review of techniques to monitor remission of acute Charcot neuroarthropathy in people with diabetes. Diabetes/Metabol Res Rev. 2020;36(7):e3328. https://doi.org/10.1002/dmrr.3328

Pinzur MS, Evans A. Health-related quality of life in patients with Charcot foot. Am J Orthop (Belle Mead NJ). 2003;32(10):492-496.

Simon SR, Tejwani SG, Wilson DL, Santner TJ, Denniston NL. Arthrodesis as an early alternative to nonoperative management of Charcot arthropathy of the diabetic foot. J Bone Joint Surg - Ser A. 2000;82(7):939-950. https://doi.org/10.2106/00004623-200007000-00005

Grant WP, Garcia-Lavin S, Sabo R. Beaming the columns for Charcot diabetic foot reconstruction: a retrospective analysis. J Foot Ankle Surg. 2011;50(2):182-189. https://doi.org/10.1053/j.jfas.2010.12.002

Albright RH, Joseph RM, Wukich DK, Armstrong DG, Fleischer AE. Is reconstruction of unstable midfoot charcot neuroarthropathy cost effective from a US payer's perspective? Clin Orthop Relat Res. 2020;478(12):2869-2888. https://doi.org/10.1097/corr.0000000000001416

Schneekloth BJ, Lowery NJ, Wukich DK. Charcot neuroarthropathy in patients with diabetes: an updated systematic review of surgical management. J Foot Ankle Surg. 2016;55(3):586-590. https://doi.org/10.1053/j.jfas.2015.12.001

Raspovic KM, Wukich DK. Self-reported quality of life in patients with diabetes: a comparison of patients with and without Charcot neuroarthropathy. Foot Ankle Int. 2014;35(3):195-200. https://doi.org/10.1177/1071100713517097

Wukich DK, Sung W. Charcot arthropathy of the foot and ankle: modern concepts and management review. J Diabetes Complicat. 2009;23(6):409-426. https://doi.org/10.1016/j.jdiacomp.2008.09.004

Ahluwalia R, Bilal A, Petrova N, et al. The role of bone scintigraphy with SPECT/CT in the characterization and early diagnosis of stage 0 charcot neuroarthropathy. J Clin Med. 2020;9(12):1-14. https://doi.org/10.3390/jcm9124123

Wukich DK, Raspovic K, Liu GT, et al. Are the sanders-frykberg and brodsky-trepman classifications reliable in diabetic charcot neuroarthropathy? J Foot Ankle Surg. 2021;60(3):432-435. https://doi.org/10.1053/j.jfas.2020.03.003

Ha J, Hester T, Foley R, et al. Charcot foot reconstruction outcomes: a systematic review. J Clin Orthop Trauma. 2020;11(3):357-368. https://doi.org/10.1016/j.jcot.2020.03.025

Vasukutty N, Jawalkar H, Anugraha A, Chekuri R, Ahluwalia R, Kavarthapu V. Correction of ankle and hind foot deformity in Charcot neuroarthropathy using a retrograde hind foot nail-The Kings' Experience. Foot Ankle Surg. 2018;24(5):406-410. https://doi.org/10.1016/j.fas.2017.04.014

Kroin E, Chaharbakhshi EO, Schiff A, Pinzur MS. Improvement in quality of life following operative correction of midtarsal charcot foot deformity. Foot Ankle Int. 2018;39(7):808-811. https://doi.org/10.1177/1071100718762138

Wukich DK, Raspovic KM, Hobizal KB, Rosario B. Radiographic analysis of diabetic midfoot charcot neuroarthropathy with and without midfoot ulceration. Foot Ankle Int. 2014;35(11):1108-1115. https://doi.org/10.1177/1071100714547218

Wukich DK, Raspovic KM, Suder NC. Prevalence of peripheral arterial disease in patients with diabetic charcot neuroarthropathy. J Foot Ankle Surg. 2016;55(4):727-731. https://doi.org/10.1053/j.jfas.2016.01.051

Rogers LC, Frykberg RG, Armstrong DG, et al. The Charcot foot in diabetes. Diabetes Care. 2011;34(9):2123-2129. https://doi.org/10.2337/dc11-0844

Lowery NJ, Woods JB, Armstrong DG, Wukich DK. Surgical management of Charcot neuroarthropathy of the foot and ankle: a systematic review. Foot Ankle Int. 2012;33(2):113-121. https://doi.org/10.3113/fai.2012.0113

Pinzur MS. Benchmark analysis of diabetic patients with neuropathic (Charcot) foot deformity. Foot Ankle Int. 1999;20(9):564-567. https://doi.org/10.1177/107110079902000905

Greenhagen RM, Wukich DK, Jung RH, Vardaxis V, Yoho RM. Peripheral and central bone mineral density in Charcot's neuroarthropathy compared in diabetic and nondiabetic populations. J Am Podiatr Med Assoc. 2012;102(3):213-222.

Petrova NL, Donaldson NK, Bates M, et al. Effect of recombinant human parathyroid hormone (1-84) on resolution of active charcot neuro-osteoarthropathy in diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Care. 2021;44(7):1613-1621. https://doi.org/10.2337/dc21-0008

Wukich DK, Liu GT, Raspovic K, Vicenzi F. Biomechanical performance of charcot-specific implants. J Foot Ankle Surg. 2021;60(3):440-447. https://doi.org/10.1053/j.jfas.2020.05.016

Manchanda K, Wallace SB, Ahn J, et al. Charcot midfoot reconstruction: does subtalar arthrodesis or medial column fixation improve outcomes? J Foot Ankle Surg. 2020;59(6):1219-1223. https://doi.org/10.1053/j.jfas.2020.07.001

Raspovic KM, Hobizal KB, Rosario BL, Wukich DK. Midfoot charcot neuroarthropathy in patients with diabetes: the impact of foot ulceration on self-reported quality of life. Foot Ankle Spec. 2015;8(4):255-259. https://doi.org/10.1177/1938640015585957

Milne TE, Rogers JR, Kinnear EM, et al. Developing an evidence-based clinical pathway for the assessment, diagnosis and management of acute Charcot Neuro-Arthropathy: a systematic review. J Foot Ankle Res. 2013;6(1):30. https://doi.org/10.1186/1757-1146-6-30

Petrova NL, Dew TK, Musto RL, et al. Inflammatory and bone turnover markers in a cross-sectional and prospective study of acute Charcot osteoarthropathy. Diabet Med. 2015;32(2):267-273. https://doi.org/10.1111/dme.12590

Petrova NL, Foster AV, Edmonds ME. Difference in presentation of charcot osteoarthropathy in type 1 compared with type 2 diabetes. Diabetes Care. 2004;27(5):1235-1236. https://doi.org/10.2337/diacare.27.5.1235-a

McGregor PC, Lyons MM, Pinzur MS. Quality of life improvement following reconstruction of midtarsal charcot foot deformity: a five year follow-up. Iowa Orthop J. 2022;42(1):109-112. https://doi.org/10.1177/2473011421s00358

Kroin E, Schiff A, Pinzur MS, Davis ES, Chaharbakhshi E, DiSilvio FA, Jr. Functional impairment of patients undergoing surgical correction for charcot foot arthropathy. Foot Ankle Int. 2017;38(7):705-709. https://doi.org/10.1177/1071100717701233

Finkler ES, Kasia C, Kroin E, Davidson-Bell V, Schiff AP, Pinzur MS. Pin tract infection following correction of charcot foot with static circular fixation. Foot Ankle Int. 2015;36(11):1310-1315. https://doi.org/10.1177/1071100715593476

Gil J, Schiff AP, Pinzur MS. Cost comparison: limb salvage versus amputation in diabetic patients with charcot foot. Foot Ankle Int. 2013;34(8):1097-1099. https://doi.org/10.1177/1071100713483116

Jeffcoate WJ, Bus SA, Game FL, et al. Reporting standards of studies and papers on the prevention and management of foot ulcers in diabetes: required details and markers of good quality. Lancet Diabetes Endocrinol. 2016;4(9):781-788. https://doi.org/10.1016/s2213-8587(16)30012-2

Alonso-Coello P, Oxman AD, Moberg J, et al. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: clinical practice guidelines. BMJ. 2016;353:i2089. https://doi.org/10.1136/bmj.i2089

Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926. https://doi.org/10.1136/bmj.39489.470347.ad

Schunemann H, Brozek J, Guyatt G, Oxman AD. GRADE Handbook; 2013. https://gdt.gradepro.org/app/handbook/handbook.html

Armstrong DG, Lavery LA, Liswood PJ, Todd WF, Tredwell JA. Infrared dermal thermometry for the high-risk diabetic foot. Phys Ther. 1997;77(2):169-177. https://doi.org/10.1093/ptj/77.2.169

Chantelau E. The perils of procrastination: effects of early vs. delayed detection and treatment of incipient Charcot fracture. Diabet Med. 2005;22(12):1707-1712. https://doi.org/10.1111/j.1464-5491.2005.01677.x

Chantelau E, Poll LW. Evaluation of the diabetic charcot foot by MR imaging or plain radiography--an observational study. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc. 2006;114(8):428-431. https://doi.org/10.1055/s-2006-924229

Chantelau E, Richter A, Ghassem-Zadeh N, Poll LW. Silent bone stress injuries in the feet of diabetic patients with polyneuropathy: a report on 12 cases. Arch Orthop Trauma Surg. 2007;127(3):171-177. https://doi.org/10.1007/s00402-006-0271-x

Chantelau EA, Richter A. The acute diabetic Charcot foot managed on the basis of magnetic resonance imaging--a review of 71 cases. Swiss Med Wkly. 2013;143:w13831. https://doi.org/10.4414/smw.2013.13831

Fosbol M, Reving S, Petersen EH, Rossing P, Lajer M, Zerahn B. Three-phase bone scintigraphy for diagnosis of Charcot neuropathic osteoarthropathy in the diabetic foot - does quantitative data improve diagnostic value? Clin Physiol Funct Imag. 2017;37(1):30-36. https://doi.org/10.1111/cpf.12264

Ruotolo V, Di Pietro B, Giurato L, et al. A new natural history of charcot foot: clinical evolution and final outcome of stage 0 charcot neuroarthropathy in a tertiary referral diabetic foot clinic. Clin Nucl Med. 2013;38(7):506-509. https://doi.org/10.1097/rlu.0b013e318292eecb

Gough A, Abraha H, Li F, et al. Measurement of markers of osteoclast and osteoblast activity in patients with acute and chronic diabetic Charcot neuroarthropathy. Diabet Med. 1997;14(7):527-531. https://doi.org/10.1002/(sici)1096-9136(199707)14:7<527::aid-dia404>3.0.co;2-q

Folestad A, Alund M, Asteberg S, et al. IL-17 cytokines in bone healing of diabetic Charcot arthropathy patients: a prospective 2 year follow-up study. J Foot Ankle Res. 2015;8(1):39. https://doi.org/10.1186/s13047-015-0096-3

Petrova NL, Moniz C, Elias DA, Buxton-Thomas M, Bates M, Edmonds ME. Is there a systemic inflammatory response in the acute charcot foot? Diabetes Care. 2007;30(4):997-998. https://doi.org/10.2337/dc06-2168

Schara K, Stukelj R, Krek JL, et al. A study of extracellular vesicle concentration in active diabetic Charcot neuroarthropathy. Eur J Pharm Sci. 2017;98:58-63. https://doi.org/10.1016/j.ejps.2016.09.009

Hingsammer AM, Bauer D, Renner N, Borbas P, Boeni T, Berli M. Correlation of systemic inflammatory markers with radiographic stages of charcot osteoarthropathy. Foot Ankle Int. 2016;37(9):924-928. https://doi.org/10.1177/1071100716649173

Armstrong DG, Lavery LA. Monitoring healing of acute Charcot's arthropathy with infrared dermal thermometry. J Rehabil Res Dev. 1997;34(3):317-321.

Zampa V, Bargellini I, Rizzo L, et al. Role of Dynamic MRI in the follow-up of acute Charcot foot in patients with diabetes mellitus. Skeletal Radiol. 2011;40(8):991-999. https://doi.org/10.1007/s00256-010-1092-0

Moura-Neto A, Fernandes TD, Zantut-Wittmann DE, et al. Charcot foot: skin temperature as a good clinical parameter for predicting disease outcome. Diabetes Res Clin Pract. 2012;96(2):e11-e4. https://doi.org/10.1016/j.diabres.2011.12.029

Chantelau E.-A, Antoniou S, Zweck B, Haage P. Follow up of MRI bone marrow edema in the treated diabetic Charcot foot - a review of patient charts. Diabet Foot Ankle. 2018;9(1):1466611. https://doi.org/10.1080/2000625x.2018.1466611

Schlossbauer T, Mioc T, Sommerey S, Kessler SB, Reiser MF, Pfeifer KJ. Magnetic resonance imaging in early stage charcot arthropathy: correlation of imaging findings and clinical symptoms. Eur J Med Res. 2008;13(9):409-414.

Griffiths DA, Kaminski MR. Duration of total contact casting for resolution of acute Charcot foot: a retrospective cohort study. J Foot Ankle Res. 2021;14(1):44. https://doi.org/10.1186/s13047-021-00477-5

Kimmerle R, Chantelau E. Weight-bearing intensity produces charcot deformity in injured neuropathic feet in diabetes. Exp Clin Endocrinol Diabetes. 2007;115(6):360-364. https://doi.org/10.1055/s-2007-970578

Fejfarova V, Jirkovska A, Krizova M, Skibova J. The effect of removable total contact cast therapy on healing of patients with diabetic foot ulcers, acute Charcot osteoarthropathy and neuropathic fractures. Vnitrni Lek. 2005;51(9):988-994.

Christensen TM, Gade-Rasmussen B, Pedersen LW, Hommel E, Holstein PE, Svendsen OL. Duration of off-loading and recurrence rate in Charcot osteo-arthropathy treated with less restrictive regimen with removable walker. J Diabetes Complicat. 2012;26(5):430-434. https://doi.org/10.1016/j.jdiacomp.2012.05.006

De Souza LJ. Charcot arthropathy and immobilization in a weight-bearing total contact cast. J Bone Joint Surg - Ser A. 2008;90(4):754-759. https://doi.org/10.2106/jbjs.f.01523

Fabrin J, Larsen K, Holstein PE. Long-term follow-up in diabetic charcot feet with spontaneous onset. Diabetes Care. 2000;23(6):796-800. https://doi.org/10.2337/diacare.23.6.796

Parisi MCR, Godoy-Santos AL, Trevisan Ortiz R, et al. Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing. Diabet Foot Ankle. 2013;4(1):22487. https://doi.org/10.3402/dfa.v4i0.22487

Sinacore DR. Acute Charcot arthropathy in patients with diabetes mellitus: healing times by foot location. J Diabetes Complicat. 1998;12(5):287-293. https://doi.org/10.1016/s1056-8727(98)00006-3

Bem R, Jirkovská A, Fejfarová V, Skibová J, Jude EB. Intranasal calcitonin in the treatment of acute Charcot neuroosteoarthropathy: a randomized controlled trial. Diabetes Care. 2006;29(6):1392-1394. https://doi.org/10.2337/dc06-0376

Bharath R, Bal A, Sundaram S, et al. A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus. Indian J Endocrinol Metabol. 2013;17(1):110-116. https://doi.org/10.4103/2230-8210.107818

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.

Jude EB, Selby PL, Burgess J, et al. Bisphosphonates in the treatment of charcot neuroarthropathy: a double-blind randomised controlled trial. Diabetologia. 2001;44(11):2032-2037. https://doi.org/10.1007/s001250100008

Pakarinen T.-K, Laine H.-J, Maenpaa H, Mattila P, Lahtela J. The effect of zoledronic acid on the clinical resolution of Charcot neuroarthropathy: a pilot randomized controlled trial. Diabetes Care. 2011;34(7):1514-1516. https://doi.org/10.2337/dc11-0396

Pitocco D, Ruotolo V, Caputo S, et al. Six-month treatment with alendronate in acute Charcot neuroarthropathy: a randomized controlled trial. Diabetes Care. 2005;28(5):1214-1215. https://doi.org/10.2337/diacare.28.5.1214

Busch-Westbroek TE, Delpeut K, Balm R, et al. Effect of single dose of RANKL antibody treatment on acute charcot neuro-osteoarthropathy of the foot. Diabetes Care. 2018;41(3):e21-e2. https://doi.org/10.2337/dc17-1517

Demographic and Clinical Characteristics of Patients With Charcot Neuro-Osteoarthropathy in People With Diabetes Mellitus in Six Countries: A Multicenter Observational Study From 1996 to 2022