Medical Treatment of Charcot’s Arthropathy

Abstract

Charcot’s arthropathy is a devastating condition affecting diabetic patients with peripheral neuropathy, resulting in a foot at risk for ulceration and amputation. Early diagnosis is important for the institution of appropriate treatment, which may help prevent disease progression and foot deformity. This article discusses the pathogenesis and treatment options available for the disorder.

Charcot’s arthropathy is not uncommon in diabetic patients with peripheral neuropathy.[1] It can be a devastating condition that may result in severe foot deformity, ulceration, and amputation. Charcot’s arthropathy mainly affects the joints and bones of the feet in diabetic patients with severe peripheral neuropathy, along with features of autonomic neuropathy. Peripheral circulation is usually normal. Diabetes mellitus is the most common cause of Charcot’s foot in the Western world,[2] and increased awareness of Charcot’s arthropathy may facilitate earlier diagnosis and institution of appropriate treatment that may prevent severe deformity and disability.

The etiology of the Charcot process is poorly understood. Predisposing factors include peripheral sensorimotor neuropathy, autonomic neuropathy, intact peripheral circulation, and trauma, which at times is so trivial that the patient cannot recall the precipitating event. Charcot changes are more likely to develop in bones with preexisting diabetic osteopenia.[3-5] The increased blood flow, as a result of autonomic neuropathy, is thought to increase the osteoclastic activity in the bone of the foot. This has been demonstrated by an increase in bone turnover markers in patients with Charcot’s arthropathy.[6,7] Gough et al[6] measured pyridinoline cross-linked carboxy-terminal telopeptide domain of type 1 collagen (1CTP) and carboxy-terminal propeptide of type 1 collagen (P1CP) as possible markers of bone resorption and bone formation, respectively, in the systemic circulation and foot of diabetic patients with acute and chronic Charcot’s arthropathy and in control subjects. The authors found an increase in the bone turnover marker 1CTP in patients with acute Charcot’s arthropathy but no difference in the bone formation markers. There was also no significant difference in the markers measured in the plasma obtained from a vein in the forearm and in the foot. In a similar study, Selby et al[7] measured urinary deoxypyridinoline (bone resorption marker) and bone-specific alkaline phosphatase (bone formation marker) in patients with acute Charcot’s arthropathy and non-Charcot’s patients with diabetes. The authors found an increase in both of these markers, indicating an ongoing remodeling process of bone resorption and formation. Therefore, a possible logical step in the treatment would be to dampen down this enhanced bone remodeling, thus retarding the progression of the Charcot process.

Management of the Charcot foot is difficult. Thus far, no specific treatment has been found to reduce or reverse the destructive changes. The treatment modalities can be divided into three groups: immobilization, radiotherapy, and pharmacologic treatment.

Currently, long-term immobilization in a plaster-of-Paris total-contact cast,[8] a Charcot Restraint Orthotic Walker,[9] or a Scotch-cast boot[2] is usually advised. The first is used mostly in the United States and in some centers in the United Kingdom; the last is used mainly in the United Kingdom. In the United States, immobilization is usually recommended for up to 1 year. In the United Kingdom, the Scotch-cast boot is used in the acute phase. Subsequently, when the Charcot process is quiescent, custom-fitted shoes with a molded insole are recommended.

Two studies have investigated the use of total-contact casting in the treatment of the Charcot foot. Armstrong et al[8] examined the use of total-contact casting in acute Charcot’s arthropathy; all patients were treated with serial total-contact casting until quiescence. Following casting, patients were put into a removable cast walker for unprotected weightbearing and then transferred to prescription footwear. Patients were transferred to cast walkers when the temperature difference between the affected site and the corresponding site on the contralateral limb was less than 1°C for 2 consecutive weeks. Patients were transferred to prescription footwear when the temperature of both limbs had remained the same (±1°C) for 1 month. The feet of all of the patients became quiescent at around 4 months (range, 4 to 56 weeks); progression to protective footwear took just over 6 months.

McCrory et al[10] also examined the role of casting and foot temperature in active Charcot’s arthropathy. The authors observed that skin temperature may not be a useful indicator of healing or progression of Charcot’s foot. However, they did find that radiographic healing usually began by 3 to 6 months, which roughly correlated with the time when “foot cooling” began. Therefore, it can be concluded from these two studies that casting is required for a minimum of 6 months, but clinical indicators are required to ascertain the total duration of immobilization. No studies have been published on the use of the Scotch-cast boot in acute Charcot’s arthropathy.

In the first randomized clinical trial of treatment of the Charcot foot, Chantelau and Schnable[11] examined the use of radiotherapy in the acute Charcot foot. Fourteen patients were randomly assigned to receive radiotherapy or sham radiotherapy in this study. All of the patients received standard treatment consisting of off-loading and bed rest. The end points of the study were clinical and radiographic healing of the Charcot foot. The authors found that patients who received radiotherapy demonstrated healing of the Charcot foot in 5.5 months, as compared with 7 months in patients who received the placebo therapy. This could have been a type 2 error resulting from the small number of patients in the study. Patients who complied with off-loading, however, did much better than noncompliant patients. This small study makes it difficult to rule out radiotherapy as a possible treatment for Charcot’s arthropathy, and further studies are required to determine the usefulness of this treatment modality for this condition.

Until recently, no pharmacologic treatment was available for the Charcot foot, and only one clinical trial has been conducted to assess the efficacy of pharmacologic treatment of Charcot’s arthropathy. An open-label study indicated the potential benefit of a bisphosphonate, pamidronate, in reducing disease activity and bone turnover markers.[12] The effect of pamidronate on foot temperature and alkaline phosphatase was studied in a small number of patients (n = 6) in this uncontrolled trial. All of the patients received infusions of pamidronate every 2 weeks, and temperature and alkaline phosphatase measurements were taken at each visit. The treatment was associated with an improvement in the patients’ symptoms and a reduction in foot temperature. A significant reduction (25%) in alkaline phosphatase was also seen over the 12-week follow-up period. Because this was an open-label trial involving a small number of patients, a randomized trial was then begun in the United Kingdom.

In the first randomized trial of pharmacologic treatment, 39 patients received placebo (normal saline solution) or pamidronate (90 mg) as a single intravenous infusion at baseline. Disease activity (temperature differential), patients’ symptoms, and bone turnover markers were assessed at baseline and at ten subsequent visits over the next 12 months. All of the patients received standard treatment of the affected foot, which included immobilization and bed rest. The patients all demonstrated a reduction in temperature and symptom scores by the end of the study period.[13] There was a statistically significant reduction in temperature in both the placebo and active groups compared with baseline. However, although the temperature reduction was greater in the active group, the difference did not reach statistical significance. Symptom scores were significantly reduced in the treatment group as compared with the placebo group. There was also a significant reduction in the bone resorption (urinary deoxypyridinoline) and bone formation (bone-specific alkaline phosphatase) markers. This effect of pamidronate was limited, and the bone markers returned to baseline levels 6 to 12 months after the infusion.

Conclusion

Immobilization is an effective treatment for the active Charcot foot. However, the effect of pamidronate on the active Charcot foot is greater with regard to reduction of symptoms than with regard to decreasing disease activity. Whether larger or more frequent doses may be more beneficial requires further study.

Practitioners must have a high index of suspicion to prevent the severe deformity caused by the Charcot process. When a patient presents with a red, swollen, inflamed foot, Charcot’s arthropathy should be suspected and appropriate treatment initiated in the absence of any other diagnosis. Treatment must be started early, as once the bony changes set in, they cannot be reversed. Therefore, immobilization and bed rest, and possibly pamidronate, should be initiated earlier rather than later if deformity and morbidity in diabetic patients with peripheral neuropathy are to be minimized.