Can Bisphosphonates Lead To Better Charcot Treatment?
Researchers saw clinical improvement within six months (two infusions). During this time, bone and joint destruction had ceased and the physicians saw gradual signs of a reconstructive healing process in the previously affected sites. However, many aspects of this case indicated the patient was in the chronic phase of Charcot. Furthermore, the study never determined markers of bone turnover and skin temperature measurements. Lastly, the initial clinical exam failed to mention erythema or increased temperature of the affected foot.
Young et. al., reported on two cases in which patients were determined had Charcot neuroarthropathy. In addition to noting increased skin temperature of greater than 2o and edema, researchers determined the patients’ condition via bone density scanning, bone scans, measuring temperature differentials and serial radiography. Doctors treated the patients with immobilization and intravenous pamidronate.
The patients with acute Charcot who were treated with immobilization and bisphosphonates had a shorter acute phase, according to Young. The author gave three infusions of pamidronate every two weeks. By the third infusion, Young was able to achieve resolution of the clinical markers of activity as measured by skin temperature differences.
These three reports of bisphosphonate therapy hold promise that inhibiting osteoclastic activity actually can arrest the destructive changes associated with the acute phase of Charcot neuroarthropathy. Immobilizing the affected limb is still the cornerstone of treatment during this phase as it will help you prevent progression of the hyperemia and subsequent fractures. You would best perform future studies to assess the effectiveness by treating an experimental group with immobilization and bisphosphonates and compare the group with a control group treated with immobilization only.
Are Not Created Equal
When you consider bisphosphonate therapy for acute Charcot neuroarthropathy, it is important also to consider the actual bisphosphonate used, since their mechanisms of action and efficacies appear to be slightly different. The three studies cited previously utilized pamidronate, but it is important to point out that the three reports were European studies and pamidronate is the most popular bisphosphonate in Europe. In the United States, alendronate, a newer drug, is the most commonly used bisphosphonate.
To compare the two drugs, look at their effectiveness at treating Paget’s disease of bone because this is the only indication common to both. Clinical studies indicate that alendronate (administered as 40mg tablets orally once a day for six months) leads to a 65 percent or greater decrease of serum alkaline phosphatase in 85 percent of patients within six months of treatment. Pamidronate (30mg administered intravenously over four hours for three consecutive days) decreased serum alkaline phosphatase by at least 50 percent in 61 percent of patients with a median of one month of treatment.
Pamidronate appears to act more rapidly than alendronate at decreasing bone resorption, but it was less efficacious. Be aware conservative treatment with both pamidronate and alendronate possibly may be more effective than either treatment alone. Certainly this is speculation, but concomitant use of both is not contraindicated.
The notion that bisphosphonate therapy would benefit patients with acute Charcot seems plausible. Although the literature on this topic is sparse and largely anecdotal, it is an impetus to perform well-planned prospective studies to determine if this type of therapy is beneficial.
Without doubt, emphasizing immobilization during the acute phase is key to preventing progressive and severe structural deformity. However, if bisphosphonates can help minimize the osseous changes, which predispose patients to pathological fractures and subsequent deformity, then it should become part of the standard regimen.
Dr. Steinberg is an Assistant Professor in the Department of Orthopaedics/ Podiatry Service at the University of Texas Health Science Center.
Mr. Rogers is a fourth-year student at Des Moines University College of Podiatric Medicine and Surgery.