take into account the simultaneous reduction in foot temperatures with simple offloading.44 Therefore, we now feel that a larger clinical trial would be required to assess if bisphosphonates affect disease activity in CN and to determine the appropriate dose, duration and frequency of treatment.
Further trials will also be needed to study other possible routes of administration, since in recent years potent oral bisphosphonates have become available.
There have been two further trials to study the benefit of bisphosphonates in CN.
In a separate study, Anderson et al. treated 23 patients with acute CN with intravenous pamidronate (variable dose) or with standard care only.45 Patients were followed up at 2 days and 2 weeks.
Patients in the pamidronate group had a greater reduction in temperature than the standard care group.
Patients also had a significant reduction in alkaline phosphatase.
This however was not a randomised study, and there was a bias in the treatment strategy.
In a study from Italy, patients with acute CN were randomised to the oral bisphosphonate alendronate (70 mg once a week) or placebo.46 Patients in both groups had reduction in temperature at the end of 6 months, which was not different; but patients in the active arm had a significant reduction in symptoms as well as a reduction in ICTP and hydroxyproline.
Patients who received alendronate also showed an improvement in bone density in the foot.
From the above studies, it has been demonstrated that bisphosphonates do have some beneficial effects on the underlying Charcot process.
However, all the studies had a small number of patients and larger randomised trials are urgently needed.
CONCLUSION CN is a debilitating condition that requires prompt diagnosis and treatment.
One can conclude from previous studies that immobilisation is an effective treatment for the active Charcot foot.
The underlying pathogenesis is thought to be enhanced bone resorption, and there have been three trials using bisphosphonates as possible pharmacological treatment.
Although some studies showed improvement in symptoms and bone turnover, a systematic improvement in disease activity has not been demonstrated.
However, all the studies were underpowered and more robust trials are indicated.
Irrespective of the treatment instituted, it must be started early in the disease process because once the bony changes and deformity have occurred they cannot be reversed.
Therefore, immobilisation, bedrest, offloading and possibly pamidronate should be initiated as soon as possible and immediately after the diagnosis has been made, if one is to reduce the Charcot joint deformity and morbidity in diabetic patients with peripheral neuropathy.