NEW YORK, New York—Recent reports suggesting a link between bisphosphonates, especially intravenous bisphosphonates, and osteonecrosis of the jaw (ONJ), have sparked rising concern among rheumatologists, oncologists, and dental surgeons, as well as in the consumer press.¹ In response, the leadership of the American Society of Bone and Mineral Research (ASBMR) is convening a multidisciplinary, international task force to examine this "emerging and urgent clinical problem."²

"Further research is needed to better understand the incidence and pathophysiology of ONJ, to rigorously study the association with intravenous and oral bisphosphonates, and to identify specific patient risk factor sets when these drugs are used in the doses recommended for treatment of osteoporosis and Paget's disease," Elizabeth Shane, MD, et al write in an editorial in the Journal of Bone and Mineral Research ²

First Job: Develop a Case Definition

The first job of the ASBMR Task Force for Osteonecrosis of the Jaw will be to recommend a provisional case definition of ONJ as the basis for subsequent work. "There is no universally accepted definition of ONJ. However, clinically it typically appears as an area of exposed alveolar bone that can occur in the mandible or the maxilla. It may or may not be painful and may or may not be associated with infection or local trauma. This area of exposed alveolar bone has most often developed after a recent tooth extraction or oral contusion/abrasion," Dr. Shane writes.

The first cases of ONJ in association with bisphosphonates were reported in 2003 and occurred in cancer patients treated with high doses of intravenous bisphosphonates. However, Dr. Shane points out that about 30 cases have been reported in patients treated with oral bisphosphonates for osteoporosis and five cases in patients taking bisphosphonates for Paget's disease.

Recently reviewing ONJ, Drs. Catherine Van Poznak and Brent B. Ward, of the University of Michigan Comprehensive Cancer Center in Ann Arbor, noted that intravenous bisphosphonate therapy "can decrease the risk of skeletal-related events and help manage bone pain" in patients with multiple myeloma or solid tumors involving the bone."³ 

These beneficial results are due to the bisphosphonates' inhibition of osteoclast activity. Dr. Van Poznak suggests that such osteoclast inhibition might also render the jaw bone vulnerable to osteonecrosis by reducing its ability to repair and remodel in response to damage caused by the physiological stress of chewing. She also points out that the jaw bone is "unique in that it is exposed to the external environment by the presence of teeth."⁴

Recommendations for Osteoporosis Patients Taking Bisphosphonates
Both authors agree that existing data suggest a very low risk of developing ONJ for patients taking oral bisphosphonates for osteoporosis; however, the lack of any reliable treatment for stopping the process once it begins heightens the importance of prevention. The ASBMR task force hopes to develop recommendations for clinical management once the diagnosis of ONJ has been made. Meanwhile, Shane and colleagues recommend:

The JBMR editorial was also endorsed by the American College of Rheumatology, the American Association of Clinical Endocrinologists, the Canadian Society of Endocrinology and Metabolism, the Endocrine Society, the European Calcified Tissue Society, the International Bone and Mineral Society, the International Society of Clinical Densitometry, the National Osteoporosis Foundation, Osteoporosis Canada, and the Paget Foundation, as well as by the journals Bone and Osteoporosis International.

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