Management of CN is difficult and there is no specific treatment that can reduce or reverse the destructive changes.
An increased awareness of this condition may help in enabling an earlier diagnosis, instituting earlier treatment and possibly preventing progression of the foot deformity and disability.
The treatment offered to patients is usually long-term immobilisation in a total contact cast (TCC; made of plaster of Paris or fibreglass), Charcot restraint orthotic walker (CROW) or a Scotchcast boot (SCB; made of Deltalite plaster).6,29,31 Two studies have shown that immobilisation may be necessary for between 14 and 18 weeks, but occasionally immobilisation for up to a year may be necessary.
More recently, pneumatic walking braces have also been used and have been shown to reduce pressures similarly as plaster casting.32 Surgical treatment has no role in the acute Charcot foot, but in the later stages, when the foot has achieved a stable shape, surgery may be necessary to remove bony deformities, and more extensive reconstructive surgery has, in some centres, led to excellent clinical results.
Tech- niques include arthrodesis, exostectomies, reconstruction and Achilles tendon lengthening33 (Chapter 23).
Immobilisation Two studies have examined the use of TCC in the treatment of the Charcot foot. In one study, Armstrong and colleagues assessed the efficacy of serial TCC in 55 patients with acute CN until quiescence.6 Following casting, patients were put into unprotected weight bearing via a removable cast walker, and then transferred to prescription footwear. Patients were transferred to cast walker when their temperature differential was less than 1◦ C for two consecutive
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weeks at the affected site compared with the corresponding site, contralaterally, and then to prescription footwear when temperature differential equilibrated for 1 month (±1◦ C).
All patients’ feet became quiescent around 4 months (range 4, 56 weeks) and progression to permanent footwear took just over 6 months.
Therefore, the mean duration of immobilisation prior to return to permanent footwear was approximately 6 months, but some patients required this treatment for up to 12 months.
In a separate study, McCrory et al. similarly examined the role of casting and foot temperature in active Charcot arthropathy.34 In this study, they observed that skin temperature was possibly not a useful indicator of Charcot healing or progression.
However, they found that radiographic healing usually began by 3, 6 months and this roughly correlated around the time when ‘foot cooling’ began.
Therefore, from these two studies, one can conclude that casting is necessary for a prolonged period, and clinical indicators are required to definitely ascertain the total duration of immobilisation.
However, there have been no published studies on the use of the SCB in the acute Charcot foot.
Radiotherapy and Ultrasound In the first randomised clinical trial in the CN, Chantelau et al. examined the use of radiotherapy in the acute Charcot foot.35 In this study, they randomised 14 patients to receive radiotherapy or sham radiotherapy.
All patients received standard treatment, which was offloading and bedrest.
The end points of the study were clinical and radiological healing of the Charcot foot.
There was no difference in healing of the Charcot foot in patients who received active treatment (radiotherapy) or sham radiotherapy (5.5 months vs 7 months; p > 0.05).
This could have been a type 2 error resulting from the small number of patients in the study.
However, patients who complied with offloading did much better than patients who were non-compliant.
From this small study, it is difficult to rule out radiotherapy as a possible treatment of CN, and further studies are required to ascertain the usefulness of this modality of treatment in this condition.
Low-intensity ultrasound has also been investigated in conjunction with offloading and was found to be useful.36 However, both the above studies were done in small groups of patients and should be investigated in more robust trials.
Pharmacological Treatment , Bisphosphonates Currently, treatments that are being used for the Charcot foot are unsatisfactory and do not modify the natural history of the condition or arrest the underlying bone resorption.
There is no pharmacological treatment licensed for the treatment of CN.
Although treatment with offloading has some clinical benefit, there is a need for pharmacological treatment.
In 1994, Selby and colleagues conducted a pilot study in the treatment of CN using a bisphosphonate, pamidronate.37 This open-label study was designed to study the effect of bisphosphonates on the disease activity in CN and also on bone turnover markers.
The effect of pamidronate on foot temperature and alkaline phosphatase was studied in a small number of patients (n = 6).
All patients received infusions of pamidronate every 2 weeks (60 mg first dose and subsequently 30 mg fortnightly over 12 weeks), and foot temperature and alkaline phosphatase were measured at each visit.
The treatment was associated with improvement in the patients’ symptoms as well as a reduction in foot temperatures.
A significant reduction was
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270 CHARCOT FOOT
also seen in alkaline phosphatase over the 12 weeks of follow-up, which fell by about 25% at the end of the study.
Bisphosphonates are synthetic analogues of inorganic pyrophosphate that inhibit bone turnover by decreasing the resorption of bone.
They do this directly, by inhibiting the re- cruitment and function of osteoclasts (the bone-resorbing cells), and indirectly, by stimulating osteoblasts (bone-forming cells).38 Bisphosphonates may also shorten the lifespan of osteo- clasts.
Increased bone resorption is a prominent feature of many bone diseases, including CN.
These characteristics make bisphosphonates the logical treatment for this condition.
Pain is a major feature in CN, and it has been suggested that processes that affect the structure of bone are not necessarily those responsible for rapid pain relief, which is seen in CN patients.39 Pain relief is thought to result from the effects of the bisphosphonate on prostaglandin E2 and other nociceptive substances.40 Bisphosphonates may also affect the release of neuropeptides and neuromodulators from afferent nerve endings, the cytokines that could be responsible for producing vasodilatory and inflammatory changes seen in various bone conditions.41,42 Following on from the above pilot study, we proceeded to a randomised double-blind clinical trial using intravenous pamidronate in diabetic patients with CN.
In this trial, we recruited 39 patients with active CN who were randomised to receive either placebo (normal saline) or pamidronate (90 mg) as a single intravenous infusion at baseline.27 Disease activity (temperature differential), patients’ symptoms and bone turnover markers were assessed at baseline and at each subsequent visit over the next 12 months.
All patients received standard treatment of the affected foot, including immobilisation and bedrest.
Reduction in temperature was seen in all patients and also symptoms score improved during follow-up.27 There was a significant reduction in temperature in the placebo and active groups at 2 weeks when compared to baseline.
There was a further reduction in temperature in the pamidronate group 4 weeks after the infusion, but this did not reach statistical significance when compared to the placebo group.
All patients were asked about their symptoms related to the Charcot foot, which was scored using a visual analogue scale.
Severe neuropathic pain was a major feature in the majority of patients, with discomfort being the next most common symptom.
This has also been noted in other series.6 Patients were asked to score the symptoms on a scale of 1, 10 and this was measured quarterly.
The patients’ symptoms were significantly reduced in the pamidronate group when compared to the placebo group and this remained so until the end of the study.
Bone markers were measured to assess Charcot activity.
We measured a bone resorption marker, deoxypyridinoline (in a second-void, early-morning sample and reported as a ratio with respect to urinary creatinine), and a bone formation marker, bone-specific alkaline phosphatase (in plasma in the fasting state).
Both markers were measured at each visit.
There was a marked reduction in urinary deoxypyridinoline and bone-specific alkaline phosphatase.
A difference in these markers was seen around 4 weeks and remained until 12, 24 weeks.
This effect of pamidronate was limited and the bone markers returned towards baseline levels in 6, 12 months after the infusion.
The overall effect of pamidronate is thought to be due to a reduction in cytokines,43 hence possibly reducing the inflammation within the bones and soft tissues of the foot.
Whether this is the case in CN is interesting and needs further study.
In this study, we did not do repeat X-rays or bone scans to assess the activity within the joints and bones of the foot.44 Although we found a reduction in the temperature (disease activity), the difference between placebo and pamidronate groups did not achieve statistical significance.
To assess the number of patients required in the study, we performed power calculations that gave us a total of 38 patients to be recruited into the study in spite of which we did not find any difference in the temperature between the active and placebo groups.