Medical Management of Charcot Arthropathy PDF

review article Diabetes, Obesity and Metabolism 15: 193–197, 2013....

review article Diabetes, Obesity and Metabolism 15: 193–197, 2013. © 2012 Blackwell Publishing Ltd article review Medical management of Charcot arthropathy N. L. Petrova & M. E. Edmonds Diabetic Foot Clinic, King’s College Hospital, London, UK Charcot arthropathy is a major complication of diabetes and it poses management challenges to health care professionals. Early diagnosis and timely intervention are essential for improved outlook of these patients. Casting therapy has been accepted as the mainstay treatment of the acute Charcot foot, although there are still controversies regarding its duration, the choice of removable and non-removable device and weight-bearing casts vs. non-weight-bearing casts. Two groups of antiresorptive therapies have been evaluated in the treatment of the acute Charcot foot, bisphosphonates (intravenous and oral) and calcitonin. These therapies have clearly shown a reduction of bone turnover, although, they have not shown a significant effect on temperature reduction. Current evidence to support their use is weak. An anabolic agent to speed up clinical resolution and fracture healing may be helpful and a clinical trial to evaluate the possible benefit of 1–84 recombinant human parathyroid hormone on fracture healing in the acute Charcot foot is in progress. This paper summarises the current approach to medical management of acute Charcot arthropathy with specific emphasis on casting and pharmacological therapy. Emerging new studies of the pathogenesis of this condition are also discussed. Keywords: bisphosphonates, calcitonin, casting therapy, Charcot arthropathy, receptor activator of nuclear factor κβ ligand (RANKL), TNF-α Date submitted 4 May 2012; date of first decision 6 June 2012; date of final acceptance 28 July 2012 Charcot neuropathic arthropathy, commonly referred as the forces, oedema and inflammation, redistributes the plantar Charcot foot, is a rare but devastating complication of type pressure, limits bone and joint destruction and arrests the 1 and type 2 diabetes. It presents without warning and progression of deformity. Its overall aim is to maintain can rapidly lead to severe bone and joint destruction resulting a plantigrade foot which can then allow weight-bearing in a in horrendous foot deformity. Predisposing factors are shoe or brace. In patients with suspected Charcot feet, instant somatic and autonomic neuropathy, osteopenia and renal offloading can arrest the development of the osteoarthropathy. impairment. It classically presents as unilateral redness and A favourable outcome has been reported in patients in whom swelling of the foot. These initial signs may be underestimated casting was initiated early compared with patients with delayed by the patient because of the co-existing peripheral neuropathy presentation. Only 1 out of 11 index patients developed and only 30% report pain or discomfort at presentation. extended foot fractures and severe deformity in contrast to the Trauma is an important trigger and has been reported by 12 out of 13 control patients in whom a late diagnosis has been 22–53% of the patients [2,5]. It commonly presents in the made. These patients were treated with casting late in the mid-foot but also occurs in the forefoot and hind-foot. Rarely, course of the disease, in contrast to the remaining 11 patients in diabetes, the knee and the wrist can also be affected by in whom offloading was started immediately. Charcot arthropathy [6–8]. Although casting has been accepted as the gold standard It is extremely important to have a high index of suspicion. treatment for acute Charcot arthropathy, there are still three This should be followed by a rapid diagnosis and early controversies associated with it. Firstly, the duration of casting intervention, and with such a modern approach, many Charcot therapy, secondly the use of non-removable or removable casts feet can now be healed and deformity prevented. and thirdly should patients be weight-bearing or not. Duration of Casting Therapy. Duration of casting therapy can Medical Management vary from an average of 9 weeks to a median of 11 months The medical management of Charcot arthropathy includes according to different studies (Table 1). The response to casting therapy and treatment with bisphosphonates and casting therapy is usually monitored by clinical assessment of calcitonin. reduction of redness and swelling of the foot and by reduction of skin foot temperature difference measured by infrared Casting Therapy thermometry. The response of Charcot arthropathy to casting therapy Casting therapy is considered as the mainstay in Charcot has been evaluated by quantitative assessment of activity by foot management. It offloads the foot, reduces mechanical bone scanning and skin foot temperatures. There was a strong correlation between temperature difference and the ratio of Correspondence to: Dr Nina L. Petrova, Diabetic Foot Clinic, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. isotope uptake of the affected and non-affected foot (r = 0.90, E-mail: [email protected] p < 0.00001). More recently, the role of dynamic MRI in  14631326, 2013, 3, Downloaded from https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/j.1463-1326.2012.01671.x by Jordan Hinari NPL, Wiley Online Library on [27/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License review article DIABETES, OBESITY AND METABOLISM Table 1. Duration of casting therapy in patients treated for acute Charcot Progression from Casts to Footwear arthropathy Patients should be changed from cast to shoes when the foot skin temperature difference is less than 2 ◦ C. Casting Study Patients/Charcot feet Duration of casting immobilisation should be followed by a gradual rehabilitation Pinzur et al. 10 patients Average 9.2 weeks (range from cast treatment to suitable footwear. When the patient 8–16 weeks) comes out of the cast there will be wasting of the calf muscles De Souza 27 patients/34 feet Average 14 weeks (range and joint stiffness. It is important to be aware of the dangers 4–20 weeks) Armstrong et al. 55 patients Average 18.5 ± 10.6 weeks of reactivating the bony destruction phase by excessive rapid (range 4–56 weeks) mobilisation or protracted weight bearing in the early stages Game et al. 219 patients Median 10 months (range of rehabilitation. Too rapid mobilisation can be disastrous, 2–29 months) resulting in further bone and joint damage and can lead to Bates et al. 46 patients Median 11 months (range prolonged casting treatment. Extremely careful rehabilitation 8–17 months) should be the rule, beginning with just a few short steps in the new footwear. At this stage patients should be provided with removable bivalve casts or cast walkers which they should wear the follow-up of 40 patients treated with casting therapy for the majority of time whilst they are gradually rehabilitating acute Charcot arthropathy has been investigated. All patients into footwear. In patients with hind foot involvement, an underwent clinical and MRI follow-up at 3 monthly intervals alternative to a removable cast or a removable bivalve cast is and there was a strong correlation between clinical and MRI the Charcot restraint orthotic walker (CROW), which can aid findings in the healing of bony lesions. the transition from cast to an ankle–foot orthosis (AFO) with bespoke footwear. This is a bespoke bivalved total-contact Removable vs. Non-removable Cast. Although the superiority of device which externally fixates the ankle. The added extra non-removable to removable casting has not been evaluated in internal padding cushions the vulnerable medial malleolar area a randomised controlled study, it is generally accepted that the and thus prevents ulceration and accommodates deformity. It non-removable cast is the gold standard therapy for Charcot is used after swelling is controlled and progressive destruction arthropathy. Interestingly, an audit of the current practice, has been halted by total-contact casting. patterns in the initial management of Charcot arthropathy in In the rehabilitation phase, the patient should be instructed the United States indicated that total contact casting was the to look for swelling, redness and warmth of the foot and first choice of management in only 49% of cases , whereas encouraged to seek urgent advice as soon as possible to rule in the UK, non-removable casts at any one point of time were out relapse. If there is no increase in warmth, swelling and used only in 34% of the cases. However, this UK web-based redness then the patient can walk a few more steps the next survey of the management of acute Charcot arthropathy clearly day, and very carefully build up to a reasonable amount of confirmed a superior outcome and shorter time to resolution walking. Finally, the patient may progress to bespoke footwear in non-removable vs. removable casts. with moulded insoles. The transition from cast to shoes is a Although there are different modifications of a total contact crucial element of the treatment and this should be performed cast and no one method of its application has been universally on an individual approach. Patients need close observation to accepted, the general rule is that casts should be checked detect any relapse which will be evident from further swelling regularly and replaced as necessary. Furthermore, patients and heat in the foot and in one series of patients, relapse was should be instructed to monitor their blood glucose levels detected in 30% of the cases. and body temperature and to check casts for any stains or In the chronic stable stage, deformity needs to be cracks daily and report immediately if concerned about any accommodated, supported or corrected. Patients with Charcot cast-related complications (cast rubs, ulcers and infection). foot deformity should be followed up promptly to prevent secondary ulceration, the risk of which is fourfold higher when Weight-bearing or Non-weight-bearing Casts. There is no clear compared with the overall risk of foot ulcers in diabetic feet. evidence as to whether non-weight-bearing cast immobilisation is superior to a weight-bearing one. In a recent study, 27 patients were treated with total contact cast for Charcot Pharmacological Management arthropathy and were allowed to bear weight as tolerated and no Current therapies in the treatment of the Charcot foot aim deleterious effect from weight-bearing was reported. Strict to correct the imbalance between bone resorption and bone non-weight-bearing on the affected foot leads to increased formation. There is firm evidence that Charcot arthropathy mechanical forces of the contralateral non-affected foot and is associated with increased osteoclastic activity and indeed development of contralateral Charcot arthropathy has antiresorptive therapies have been used with some success. Two been reported in up to 40% of patients. When instituting groups of therapies have been evaluated in the treatment of the offloading therapy in a patient, it is important to consider acute Charcot foot consisting of bisphosphonates (intravenous patient’s comorbidities and risk of falls. It may be advisable and oral) and calcitonin (Table 2), [22–25]. to use crutches for supported walking and/or wheelchair These therapies have clearly demonstrated a reduction of to reduce pressure on both feet and prevent contralateral bone turnover. However, they have not shown a significant involvement. effect on temperature reduction between the active treatment 194 Petrova and Edmonds Volume 15 No. 3 March 2013  14631326, 2013, 3, Downloaded from https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/j.1463-1326.2012.01671.x by Jordan Hinari NPL, Wiley Online Library on [27/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License DIABETES, OBESITY AND METABOLISM review article Table 2. Antiresorptive therapies in acute Charcot osteoarthropathy Bisphosphonates Active substance Pamidronate Zolendronate Alendronate Calcitonin Study design Double blind randomised Double blind randomised Randomised controlled Randomised controlled control trial controlled trial trial trial Subject number 39 39 20 32 21 active/18 placebo 18 active/17 placebo 11 active/9 controls 16 active/16 controls InterventionActive/ 90 mg pamidronate in 4 mg zolendronic 70 mg alendronate/9 Salmon calcitonin control group normal saline/placebo acid/placebo control subjects 200 IU + calcium sup- (normal saline) plementation/calcium supplementation Route of administration i.v./i.v. i.v./i.v. Oral once a week/nil nasal spray + oral/oral Duration of intervention Single dose infusion for Three infusions in 6 months – weekly 6 months – daily 4h 1 month intervals Reduction in skin foot Non-significant active vs. N/A Non-significant active vs. Non-significant active vs. temperatures placebo control control Reduction in bone Significant active vs. N/A Significant active vs. Significant active vs. turnover placebo control control Reduction in symptoms Significant active vs. N/A Significant active vs. N/A placebo control Median total N/A Significant placebo vs. N/A N/A immobilisation time active N/A, not available. group and the control group [22,23,25]. Also the benefit of foot. At present, a double-blind, randomised, control study in these therapies on fracture healing and resolution of the patients with acute Charcot arthopathy to evaluate the possible arthropathy is unknown, as none of these studies reported benefit of 1–84 recombinant human parathyroid hormone on data on radiological follow-up. fracture healing is in progress. With regard to the time to clinical resolution, patients treated with zolendronic acid required significantly longer immobilisation compared with the placebo group (Table 2),. This is in agreement with recent data, which reported that Future Therapies the median time to resolution in those who received any form Recently, considerable progress has been made with our of bisphosphonates was greater compared with individuals understanding of the pathogenesis of this difficult condition. It who did not. is a bone and joint destruction, associated with increased Although some authors consider bisphosphonates as useful osteoclastic activity and uncontrolled inflammation. adjuncts to standard management , a recent systematic Advances in cellular biology have helped to elucidate the review of the treatment of acute Charcot arthropathy with mechanisms of increased osteoclastic activity in acute Charcot bisphosphonates has reported that the evidence to support arthropathy. The recently discovered receptor activator of their use is weak and indeed these therapies have not nuclear factor κβ ligand (RANKL), a cytokine from the been approved in the United States by the Food and Drug tumour necrosis factor (TNF)-ligand superfamily, has been Administration for use in patients with Charcot arthropathy identified as a key factor for osteoclast differentiation and. It is possible that the window of opportunity to administer regulation. Using an in vitro technique to generate these antiresorptive therapies is limited and there may be functional human osteoclasts from peripheral blood monocytes no definite benefit in patients who have already developed [33,34], it has been shown that newly formed osteoclasts from extensive fractures and bone fragmentation at presentation. patients with acute Charcot arthopathy exhibit an increased Another way to improve bone remodelling is to use response to RANKL in comparison with osteoclasts from an anabolic agent, as it may speed up clinical resolution diabetic patients and healthy subjects. Furthermore, this and fracture healing and an initial pilot study in acute response is modulated by the proinflammatory cytokine TNF- Charcot osteoarthropathy has evaluated the effect of human α,. This is in agreement with the recent hypothesis parathyroid hormone on fracture healing in patients with that the proinflammatory cytokines play an important role Charcot osteoarthropathy. Although this pilot observation in the inflammatory osteolysis of Charcot arthropathy. has shown more rapid fracture consolidation, faster oedema Moreover, a further study has shown increased expression control and temperature stabilisation, and earlier return to of TNF-α by activated monocytes and increased serum weight bearing , larger studies are needed to confirm the levels of TNF-α in patients with active Charcot arthropathy possible role of anabolic agents in the treatment of Charcot compared with diabetic control patients. Thus, there is an Volume 15 No. 3 March 2013 doi:10.1111/j.1463-1326.2012.01671.x 195  14631326, 2013, 3, Downloaded from https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/j.1463-1326.2012.01671.x by Jordan Hinari NPL, Wiley Online Library on [27/10/2024]. 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