Avascular necrosis of the jaws: risk factors in metastatic cancer patients. Tarassoff P, Csermak K. In his letter in the September issue of the Journal ofOral and Maxillofacial Surgery (J Oral Maxillofac Surg 61:1115–1117, 2003), Dr Marx suggested a possible association between the use of bisphosphonates such as pamidronate and zoledronic acid to the development of avascular necrosis of the jaws. The case reports cited in the letter are not adequate to suggest a causal association, much less a “growing epidemic.” A thorough review of the medical literature and our ongoing review of the reported cases reveal multiple risk factors for avascular necrosis of the jaws in cancer patients. Prior to those cases reported by Marx and others, no cases of this condition ha d been previously reported in multiple, well-controlled clinical trials of more than 3,000 cancer patients that had been conducted as far back as the early 1990s. Since their introduction, it is estimated that pamidronate and zoledronic acid have been used in approximately 2.5 million patients worldwide and reports of this condition during this extensive postmarketing experience have been rare. The treatment needs of people with cancer are generally complex, and may involve a variety of therapies such as radiation, chemotherapy, and other concomitant medications such as steroids, that are well-known and documented causes of osteonecrosis.1–3 Importantly, recognized risk factors for osteonecrosis of the jaws are common in cancer patients and include infections of dental and sinus origin, dental procedures involving the use of a local anesthetic with vasoconstrictors, and anemia. An analysis of the General Practice Research Database (GPRD) of 5.5 million patients in the United Kingdom found the incidence of osteonecrosis of all sites to be 4 times higher in the cancer patient population than in the general population. At the present time, the vast majority of cancer patients with bone metastases receive bisphosphonate therapy as a standard of care. Therefore, the concurrence of osteonecrosis in cancer patients receiving bisphosphonate therapy is not unexpected nor does it indicate a causal relationship between the two. Contrary to the author’s assertions, all bisphosphonates accumulate in the mineralized bone matrix and remain there for a long time.4 In addition, other bisphosphonates such as risedronate and alendronate contain nitrogen. However, only IV bisphosphonates are routinely used in the cancer patient population, which is at increased risk for avascular necrosis of the jaws. A careful search of more than 60 citations in the literature did not reveal any association between bisphosphonate administration and osteonecrosis in either humans or animals and support association with currently known risk factors. Indeed, several references cite the successful treatment of osteonecrosis with bisphosphonates.5,6 In conclusion, IV bisphosphonates provide important clinical benefits to patients with bone metastases, when used appropriately, and no change in clinical practice with these therapies is warranted. However, we agree that cancer patients should receive appropriate prophylactic attention to maintain their oral health. We remain committed to patient safety and will continue to monitor reports of osteonecrosis and provide this information to health authorities. 1. Schwartz HC. Osteonecrosis of the jaws: A complication of cancer chemotherapy. Head Neck Surg 1982;4:251. 2. Sung EC, Chan SM, Sakurai K, et al. Osteonecrosis of the maxilla as a complication to chemotherapy: A case report. Spec Care Dentist 2002;22:142. 3. Mirzai R, Chang C, Greespan A, et al. The pathogenesis of osteonecrosis and the relationship to corticosteriods. J Asthma 1999;36:77. 4. Fleisch H. In Bisphosphonates in Bone Disease: From the Laboratory to the Patients, Academic Press, San Diego, CA 2000, 34-55. 5. Agarwala A, Sule A, Pai BU. Alendronate in the treatment of avascular necrosis of the hip. Rheumatology 2002;41:346. 6. Astrand J, Aspenberg P. Systemic alendronate prevents resorption of necrotic bone during revascularization. A bone chamber study in rats. BMC Musculoskelet Disord 2002;3:19. J Oral Maxillofac Surg. 2003 Oct;61(10):1238-9. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.