Originally published as JCO Early Release 10.1200/JCO.2008.16.9300 on November 17 2008

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Natural History of Osteonecrosis of the Jaw in Patients With Multiple Myeloma

Ashraf Badros, Evangelos Terpos, Eirini Katodritou, Olga Goloubeva, Efstathios Kastritis, Evgenia Verrou, Kostas Zervas, Maria R. Baer, Timothy Meiller, Meletios A. Dimopoulos

From the University of Maryland, Department of Medicine, Greenebaum Cancer Center, Baltimore, MD; Greek Myeloma Study Group; Department of Hematology and Medical Research, General Air Force Hospital; Department of Clinical Therapeutics, University of Athens School of Medicine, Athens; and the Department of Hematology, Theagenion Cancer Center, Thessaloniki, Greece

Corresponding author: Ashraf Badros, MD, University of Maryland, Greenebaum Cancer Center, 22 South Greene St, Baltimore, MD 21201; e-mail: abadros{at}umm.edu

Purpose To evaluate the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma.

Patients and Methods Ninety-seven patients with myeloma from the United States (n = 37) and Greece (n = 60) were observed prospectively for a minimum 3.2 years after ONJ. Patients characteristics were similar with regard to age, bisphosphonate use, and myeloma therapy, except more autologous transplantations were performed on patients in the United States than in Greece (73% v 28%; P < .0001).

Results ONJ resolved in 60 patients (62%), resolved and recurred in 12 patients (12%), and did not heal in 25 patients (26%). Dental procedures preceded ONJ in 46 patients (47%) and were more common in those with single episodes (35 of 60, 58%) than recurrent or nonhealing (11 of 37, 30%; P = .007). Recurrent ONJ followed reinitiation of bisphosphonates in six of 12 patients. Greek patients had more bone pain than United States patients (60% v 30%, P = .001) and were less likely to restart bisphosphonates (5% v 35%, P < .0002). Myeloma relapses were more common in patients with recurrent/nonhealing than single-episode ONJ (84% v 62%; P = .02). Median overall survival from myeloma diagnosis was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single, recurrent, and nonhealing ONJ (P = .2).

Conclusion ONJ healed in 75% of patients. Patients with spontaneous ONJ have a higher risk of nonhealing and recurrence. Reinitiating bisphosphonates after healing of ONJ is a reasonable option in patients experiencing relapse who are at risk of skeletal complications. Further studies of the pathogenesis and healing of ONJ are needed.

published online ahead of print at www.jco.org on November 17, 2008

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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