Bisphosphonates are a class of drugs that inhibit the resorption or breakdown of bone tissue. Bisphosphanates are used for the prevention and treatment of osteoporosis, multiple myeloma and other conditions that involve bone fragility. In the last 10 years, millions of patients have taken biphosphanates for the prevention of osteoporosis and bone thinning from cancer. Bisphosphantes once seemed safe, but lately concerns have been raised.  Many women have been taking bisphosphantes thinking that these drugs were okay since their doctors probably did not caution them on potential risks. However, bisphosphante use is now believed to be associated with osteonecrosis of the jaw. Osteonecrosis of the jaw is an uncommon complication, but it is estimated that among the 500,000 American cancer patients who take the drugs because their disease is affecting their bones, 1 to 10 percent may develop the problem. Some dentists are refusing to treat patients taking the drugs, fearful that the dental work will induce a case of osteonecrosis, and lawyers are lining up to sue the drugs' makers, saying they failed to give patients adequate warning. Cancer patients, mostly those with multiple myeloma and breast cancer whose disease has spread to their bones, generally take one of two bisphosphonates, Zometa or the older Aredia, intravenously. Osteoporosis patients usually take bisphosphonates as pills, in much lower doses that patients with cancer. Those bisphosphanate drugs — Fosamax, Actonel and Boniva — reduce the risk of fractures of the spine or hip, injuries that can create a steady downward spiral in patients' condition.
     My thoughts: It may be too early to know for certain how prevalent and serious are the risks from bisphophanates, including osteonecrosis, but if you are taking them, ask your doctor if you really need them and whether the risks are worth the potential benefits. In previous issues I mentioned that calcium supplements at 600 mg to 1200 mg a day are beneficial, and, of course, exercise and weight lifting are the most helpful.

Osteonecrosis Research Update

Bisphosphonates and oral cavity avascular bone necrosis: a review of twelve cases.
Anticancer Res. 2006 Jul-Aug;26(4B): Department of Medical Oncology, Hospital A. Fiorini, Terracina, Italy.
 Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws. CONCLUSION: Based on the patients' respective histories, clinical presentations and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrosis is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates compromise bone vascularity may be related to their effect on the osteoclasts. The potent bisphosphonate -mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of the bone.

Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws.
Dentomaxillofac Radiol. 2006 Jul;35(4):236-43. Department of Dental Sciences, University of Trieste, Trieste, Italy.
It is important to recognize osteonecrosis of the jaw in patients treated with bisphosphonates because an early diagnosis can make a significant difference to the outcome of the disease. The aim of this study is to describe the radiological features of bisphosphonate osteonecrosis in order to aid its prompt recognition.  99Tc(m)-MDP three-phase bone scan was the most sensitive tool to detect the osteonecrosis at an early stage. CONCLUSIONS: 99Tc(m)-MDP three-phase bone scans who could be used as a screening test to detect subclinical osteonecrosis in patients who have received bisphosphonates. CT scans and MRI are useful in defining the features and extent of osteolytic lesions.

Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment.
Lancet Oncol. 2006 Jun;7(6):508-14. Department of Diagnostic Sciences, Nova Southeastern University College of Dental Medicine, Fort Lauderdale, FL
We present current knowledge of bisphosphonate -associated osteonecrosis, a new oral complication in oncology. It was first described in 2003, and hundreds of cases have been reported worldwide. The disorder affects patients with cancer on bisphosphonate treatment for multiple myeloma or bone metastasis from breast, prostate, or lung cancer. Bisphosphonate -associated osteonecrosis is characterised by the unexpected appearance of necrotic bone in the oral cavity. Osteonecrosis can develop spontaneously or after an invasive surgical procedure such as dental extraction. Patients might have severe pain or be asymptomatic. Symptoms can mimic routine dental problems such as decay or periodontal disease. Intravenous use of pamidronate and zoledronic acid is associated with most cases. Other risk factors include duration of bisphosphonate treatment (ie, 36 months and longer), old age in patients with multiple myeloma, and a history of recent dental extraction.