Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Diabetic neuropathic arthropathy

Lesley D Hordon, MD
Section Editors
Don L Goldenberg, MD
David M Nathan, MD
Deputy Editor
Paul L Romain, MD


A variety of musculoskeletal conditions have been associated with diabetes mellitus. These include specific arthropathies of the hand and shoulder, spontaneous infarction of skeletal muscle, and limited joint mobility. (See "Musculoskeletal complications in diabetes mellitus" and "Diabetic muscle infarction" and "Limited joint mobility in diabetes mellitus".)

In addition, the loss of sensation to a joint may result in a chronic, progressive, and destructive arthropathy. The prototype of this disorder was described by Charcot in relation to tabes dorsalis. Similar changes are seen with other neurologic disorders, such as syringomyelia and diabetic neuropathy. Diabetes is the most common cause of neuropathic (Charcot) arthropathy in the western world. Diabetic neuropathic arthropathy is also called diabetic osteoarthropathy.


The pathogenesis of this condition remains uncertain, but it is probably due to a combination of mechanical and vascular factors resulting from diabetic peripheral neuropathy (algorithm 1) [1-3]. As an example, lack of proprioception secondary to peripheral neuropathy may result in ligamentous laxity, increased range of joint movement, instability, and damage by minor trauma, to which the relatively insensitive neuropathic foot is prone.

An alternative theory suggests that autonomic neuropathy results in vasomotor changes and in the formation of arteriovenous shunts. These, in turn, result in reductions in effective skin and bone blood flow, despite the good and sometimes bounding foot pulses in these patients. Another unproven hypothesis is that an exaggerated local inflammatory response to trauma, mediated by proinflammatory cytokines, results in the osteoarthropathy [4].

A possible cytokine-associated effect is suggested by the finding of enhanced osteoclastic activity in surgical specimens from patients with Charcot arthropathy [5]. Other laboratory studies suggest that both receptor activator of nuclear factor (NF) kappa B (RANK) Ligand (RANKL)-dependent and -independent pathways may be involved in the increased bone resorption seen in this condition [6].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jan 2016. | This topic last updated: Feb 19, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Giurini JM, Chrzan JS, Gibbons GW, Habershaw GM. Charcot's disease in diabetic patients. Correct diagnosis can prevent progressive deformity. Postgrad Med 1991; 89:163.
  2. Brower AC, Allman RM. Pathogenesis of the neurotrophic joint: neurotraumatic vs. neurovascular. Radiology 1981; 139:349.
  3. Sinha S, Munichoodappa CS, Kozak GP. Neuro-arthropathy (Charcot joints) in diabetes mellitus (clinical study of 101 cases). Medicine (Baltimore) 1972; 51:191.
  4. Jeffcoate WJ, Game F, Cavanagh PR. The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet 2005; 366:2058.
  5. Baumhauer JF, O'Keefe RJ, Schon LC, Pinzur MS. Cytokine-induced osteoclastic bone resorption in charcot arthropathy: an immunohistochemical study. Foot Ankle Int 2006; 27:797.
  6. 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; 51:1035.
  7. Sequeira W. The neuropathic joint. Clin Exp Rheumatol 1994; 12:325.
  8. Forgács SS. Diabetes mellitus and rheumatic disease. Clin Rheum Dis 1986; 12:729.
  9. Resnick D. Neuroarthropathy. In: Diagnosis of Bone and Joint Disorders, Resnick D, Niwayama G (Eds), WB Saunders, Philadelphia 1981. p.2436.
  10. Matricali GA, Bammens B, Kuypers D, et al. High rate of Charcot foot attacks early after simultaneous pancreas-kidney transplantation. Transplantation 2007; 83:245.
  11. Slowman-Kovacs SD, Braunstein EM, Brandt KD. Rapidly progressive Charcot arthropathy following minor joint trauma in patients with diabetic neuropathy. Arthritis Rheum 1990; 33:412.
  12. Fabrin J, Larsen K, Holstein PE. Long-term follow-up in diabetic Charcot feet with spontaneous onset. Diabetes Care 2000; 23:796.
  13. Wukich DK, Sung W, Wipf SA, Armstrong DG. The consequences of complacency: managing the effects of unrecognized Charcot feet. Diabet Med 2011; 28:195.
  14. Edmonds ME, Clarke MB, Newton S, et al. Increased uptake of bone radiopharmaceutical in diabetic neuropathy. Q J Med 1985; 57:843.
  15. Seabold JE, Flickinger FW, Kao SC, et al. Indium-111-leukocyte/technetium-99m-MDP bone and magnetic resonance imaging: difficulty of diagnosing osteomyelitis in patients with neuropathic osteoarthropathy. J Nucl Med 1990; 31:549.
  16. Ahmadi ME, Morrison WB, Carrino JA, et al. Neuropathic arthropathy of the foot with and without superimposed osteomyelitis: MR imaging characteristics. Radiology 2006; 238:622.
  17. Höpfner S, Krolak C, Kessler S, et al. Preoperative imaging of Charcot neuroarthropathy in diabetic patients: comparison of ring PET, hybrid PET, and magnetic resonance imaging. Foot Ankle Int 2004; 25:890.
  18. Wukich DK, Sung W. Charcot arthropathy of the foot and ankle: modern concepts and management review. J Diabetes Complications 2009; 23:409.
  19. Frykberg RG, Zgonis T, Armstrong DG, et al. Diabetic foot disorders. A clinical practice guideline (2006 revision). J Foot Ankle Surg 2006; 45:S1.
  20. Pinzur MS, Lio T, Posner M. Treatment of Eichenholtz stage I Charcot foot arthropathy with a weightbearing total contact cast. Foot Ankle Int 2006; 27:324.
  21. Selby PL, Young MJ, Boulton AJ. Bisphosphonates: a new treatment for diabetic Charcot neuroarthropathy? Diabet Med 1994; 11:28.
  22. Jude EB, Selby PL, Burgess J, et al. Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial. Diabetologia 2001; 44:2032.
  23. Pitocco D, Ruotolo V, Caputo S, et al. Six-month treatment with alendronate in acute Charcot neuroarthropathy: a randomized controlled trial. Diabetes Care 2005; 28:1214.
  24. Pakarinen TK, Laine HJ, Mäenpää H, et al. The effect of zoledronic acid on the clinical resolution of Charcot neuroarthropathy: a pilot randomized controlled trial. Diabetes Care 2011; 34:1514.
  25. Bem R, Jirkovská A, Fejfarová V, et al. Intranasal calcitonin in the treatment of acute Charcot neuroosteoarthropathy: a randomized controlled trial. Diabetes Care 2006; 29:1392.
  26. Bono JV, Roger DJ, Jacobs RL. Surgical arthrodesis of the neuropathic foot. A salvage procedure. Clin Orthop Relat Res 1993; :14.
  27. Thompson RC Jr, Clohisy DR. Deformity following fracture in diabetic neuropathic osteoarthropathy. Operative management of adults who have type-I diabetes. J Bone Joint Surg Am 1993; 75:1765.
  28. Mueller MJ, Sinacore DR, Hastings MK, et al. Effect of Achilles tendon lengthening on neuropathic plantar ulcers. A randomized clinical trial. J Bone Joint Surg Am 2003; 85-A:1436.