Badros, A. et al. Natural history of osteonecrosis of the jaw in patients with multiple myeloma. J. Clin. Oncol. 26, 5904–5909 (2008).

A study that evaluated the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ)—an emergent problem for certain patients with cancer—found that reinitiation of bisphosphonate therapy and invasive dental procedures trigger its recurrence.

High-dose, intravenous administration of long-acting bisphosphonates can alleviate skeletal effects of multiple myeloma; however, reports of ONJ as a potential consequence of such therapy have sparked concern. The natural history of ONJ in cancer patients is, therefore, an area of intense interest. Badros et al. conducted a prospective, observational study in 97 patients with multiple myeloma who had been diagnosed with ONJ to gain insight into its progression.

Uniquely, this study compared patients from two geographic locations...

Uniquely, this study compared patients from two geographic locations: Greece and the US. Median age at cancer diagnosis was similar in the two groups, as was the median interval between diagnoses of cancer and of ONJ. However, autologous stem-cell transplants, diabetes mellitus and renal insufficiency were all more common in the US cohort than in the Greek one. The number of patients in relapse or receiving salvage therapy at the time of ONJ diagnosis was also higher in the US cohort.

Dental extractions preceded diagnosis of ONJ in 47% of cases, and these procedures were more common in patients with a single episode of ONJ than in those with recurrent and nonhealing disease (58% versus 30%). ONJ resolved in 62% of cases, recurred after healing in 12% (at the same or a new site) and did not resolve in 26% during 9 months of follow-up. The recurrence rate was higher among US patients than Greek patients (22% versus 7%, respectively). Discontinuation of bisphosphonate therapy correlated with increased bone pain in the Greek cohort, and increased fracture rates in the US cohort; patients in the US were more likely to restart bisphosphonate therapy than their Greek counterparts were. ONJ recurrence was precipitated by reinitiation of bisphosphonate therapy in six cases and dental treatment in four cases. The rate of multiple myeloma relapse was higher in patients with recurrent or unresolved ONJ than in those who experienced a single such episode.

Badros et al.'s findings provide valuable information on the possible progression of ONJ in patients with multiple myeloma. Nevertheless, would these findings translate to other populations of patients with cancer and metastatic bone disease? According to Cesar Migliorati, Professor of Oral Medicine (NOVA Southeastern University, USA), the next step might be “to conduct a controlled, randomized, prospective study similar to the present study in order to characterize general health issues, cancer and oral health, before starting bisphosphonate therapy.” Dr Migliorati further suggests that such a study could uncover important information about the pathobiology of ONJ and identify possible risks of its development.

Clinicians must weigh the risks of skeletal complications against the possibility of ONJ development. Badros et al. conclude that, until further evidence is gathered, “restarting bisphosphonates, in the setting of progressive multiple myeloma and bone disease, in patients with nonhealing ONJ or recurrent lesions, should be discussed with the patient and the decision should be individualized.”