Bisphosphonate therapy for cancer and prevalence of inflammatory jaw conditions.

See " Funding " following " References. " Patients with multiple myeloma and metastatic cancer to the bones show reduced incidence of skeletal-related events when they are treated with intravenous bisphosphonates such as pamidronate or zoledronic acid (1 , 2). For many years, the continuous, often monthly, use of bisphosphonates in such patients was not questioned. However, in 2003, an adverse reaction, termed bisphosphonate-associated osteonecrosis of the jaws, was reported in this patient population (3 , 4). To date, more than 600 cases have been reported, but it is likely that many more exist. The prevalence of osteonecro-sis of the jaws in the oncologic population was 6% – 11% in small single-center retrospective studies (5 – 7) and 4% in one web-based survey (8). The risk of development of osteonecrosis of the jaws is dependent on cumulative dose and potency of the agent (6 , 9). Patients with cancer are more likely than those with osteoporosis to develop osteonecrosis of the jaws because they receive more potent agents and more frequent dosing. Recent recommendations from the Mayo Clinic caution against indefinite use of such agents because of the occurrence of osteonecrosis of the jaws (10). The etiopathogenesis of osteonecrosis of the jaws is unknown, but severe suppression of bone turnover probably plays an important role. The study by Wilkinson et al. (11) in this issue of the Journal nicely demonstrates the strengths of pharmacoepidemiologic analyses. A large unselected group of patients with cancer, with and without a history of bisphosphonate treatment, was assembled by use of previously collected data through the Surveillance, Epidemiology, and End Results registry. Because these data include patients from referral centers and the wider community, they reduce problems of generalizability that occur in studies that rely heavily on referral populations treated at cancer centers. As well, the study database includes important information regarding comorbid conditions that may confound the relationship between bisphosphonates and jaw pathology. Finally, the use of data from thousands of patients translates into a statistically powerful study conducted relatively quickly without an enormous budget. The authors found that treatment with intravenous bisphospho-nates was associated with an increased risk of jaw or facial bone surgery and an increased risk of being diagnosed with an infl amma-tory condition or osteomyelitis of the jaw, compared with nontreat-ment (5.48% versus 0.30%, respectively, at 6 years). The risk rose with increasing cumulative dose. In another epidemiologic study that …