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Understanding Bisphosphonates in Cancer Care

by Ana Maria Lopez, MD, MPH, FACP

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Bone health is significant at multiple points in the cancer journey. Cytotoxic chemotherapy may be directly harmful to osteoclasts, the cells that make bone, thereby promoting bone loss. Combined with poor oral intake, decreased physical activity, and increased body mass index, bone health is assaulted on multiple fronts by cancer therapy.

Normal bone is in a constant state of balanced turnover. Osteoporotic bone is breaking down more than building. The most prevalent therapy for osteoporosis is a class of drugs known as bisphosphonates. Bisphosphonates impair the resorption process, resulting in improved bone density and include both oral – risedronate (Actonel®), alendronate (Fosamax®), and ibandronate (Boniva®), – and more potent intravenous preparations – pamidronate (Aredia®), and zoledronate (Zometa®),. Intravenous preparations are more available to the body and do not carry the risk of heartburn noted with the oral agents. In addition, high-potency intravenous bisphosphonates have been shown to modify progression of skeletal metastasis in several forms of cancer, especially breast cancer. They are, therefore, an area of active clinical study.

The first role for bisphosphonates in cancer care came in the treatment of disease that had spread to the bone (bone metastasis) and resulted in a statistically significant reduction in skeletal complications of bone disease, including fewer episodes where the tumor mass in the bone pushed on the spinal cord. These benefits brought about decreased use of healthcare services for treatment of bone disease: less radiation and surgical therapy within the first two years of use. Clinical data beyond two years are unavailable. However, because of their marked benefit, current recommendations do not include guidelines on when to stop bisphosphonate therapy.

Aggressive oral hygiene helps to prevent osteonecrosis of the jaw during bisphosphonate therapy.

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Dr. Ana Maria Lopez

As the use of bisphosphonates has become more prevalent, a new yet uncommon condition, osteonecrosis of the jaw (a severe bone disease that affects the jaws, including the maxilla and the mandible) has been identified as a side effect of their use. This is a significant concern for the person with cancer because more than 90 percent of the cases of ONJ appear to be related to the use of the more potent bisphosphonates that are more commonly used in oncology practice. Interestingly, clodronate, another bisphosphonate not in common use in the United States, has not been implicated in ONJ.

The most significant risk factor for the development of ONJ is prolonged exposure to bisphosphonate, three or more years. Other factors include old age, dental procedures, trauma to the jaw area, radiation therapy, chemotherapy, concomitant use of steroids, and poor dental health. Prevention strategies include removal of all potential sites of dental infection, including replacement or refitting of mouth appliances before the start of bisphosphonate therapy, and aggressive oral hygiene.

The diagnosis is primarily a clinical one and may mimic chronic periodontal infection with pain, swelling, gingivitis, loose teeth, poorly healing gums, and heaviness or numbness of the jaw. The appearance of necrotic bone requires a biopsy. A biopsy that confirms the absence of malignant cells in the presence of marked inflammation is consistent with ONJ. Radiographs are inconsistently definitive. Treatment approaches center on pain control, careful local debridement (removal) of necrotic bone, oral rinses to inhibit bacterial overgrowth, and antibiotics as needed. Infection needs to be treated appropriately with antibiotics; however, true infection must be differentiated from colonization of the bone with bacteria. Although no effective therapy has been defined, hyperbaric oxygen may be a useful adjunctive therapy.

Bone health is a concern to the person with cancer. Bisphosphonates are important adjuncts to cancer treatment to support bone health in early disease and to treat disease that has spread to the bone. Awareness of ONJ is important to all people on a bisphosphonate. Maintain your oral health. Let your dental professional know that you are on a bisphosphonate and if you have any new or unusual oral discomfort.

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Dr. Ana Maria Lopez is the associate professor of Clinical Medicine and Pathology and the medical director of the Arizona Telemedicine Program at the Arizona Cancer Center in Tucson, AZ.

This article was published in Coping® with Cancer magazine, January/February 2009.