Bisphosphonate Use and the Risk of Adverse Jaw Outcomes: A medical claims study of 714,217 people

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ABSTRACT

Background

While osteonecrosis of the jaw (ONJ) has been associated with the prolonged use of bisphosphonates (BPs), there is limited information about the risk of ONJ among users of oral BPs or about the magnitude of the risk among users of intravenous (IV) BPs.

Methods

The authors studied medical claims data from 714,217 people with osteoporosis or cancer to identify diagnostic codes or procedure codes for three outcomes: inflammatory conditions of the jaws, including osteonecrosis; major jaw surgery necessitated by necrotic or inflammatory indications; and jaw surgeries necessitated by a malignant process. The authors calculated stratified odds ratios and 95 percent confidence intervals.

Results

The results indicate that oral administration of BPs decreases the risk of adverse bone outcomes. In contrast, IV administration strongly and significantly increases the risk (P < .05) of adverse jaw outcomes or surgery. Across both osteoporosis and cancer, patients receiving IV BPs had a fourfold increased risk of having inflammatory jaw conditions and a greater than sixfold increased risk of having undergone major surgical resection in the jaw.

Conclusions

Mode of bisphosphonate use results in different risk profiles for adverse jaw outcomes. While the authors documented an increased risk of inflammatory conditions and surgical procedures of the jaw for users of IV BPs, they did not find these observed increases for users of oral BPs.

Clinical Implications

Physicians and dentists must be aware of the higher frequency of adverse jaw effects in patients receiving IV BPs, especially osteonecrosis of the jaw. While the authors' results have internal consistency, more clinical studies are needed to replicate and clarify the observed associations over long follow-up periods.

Section snippets

MATERIALS, SUBJECTS AND METHODS

The basis of this study is a medical claims database from a large national health insurance plan that provides health coverage to approximately 15 million members. The first step was to extract all medical claims data from April 2000 through April 2006 across the United States for people who had claims for International Classification of Diseases, ninth revision (ICD-9), codes for osteoporosis or cancer. For osteoporosis, the specific codes we included were ICD-9 codes 7330 (osteoporosis),

RESULTS

We analyzed medical claims from a large national health insurance plan to detect signals of risk associated with the use of a widely used class of medications, BPs. The two populations we chose to study were patients with osteoporosis, for whom orally administered BPs were indicated, and patients with certain cancers, for whom high-dose IV BPs were indicated. While low-dose IV zoledronic acid recently was approved for the management of osteoporosis, patients with cancer tend to receive doses

DISCUSSION

The limitations of claims-based analyses are many and often preclude any firm conclusions. Some of the limitations of claims-based analyses are related to the fact that the primary role of the claims database is administrative (billing and operations) and that, thus, it has not been designed for medical research. In comparison with the medical record, medical claims do not contain as many details and, at times, are prone to error. As with all observational studies, medical claims studies often

CONCLUSION

IV, but not oral, BPs seem to be strongly associated with adverse outcomes in the jaws. The increased risks reported here may reflect an increased risk of experiencing ONJ among users of IV BPs. The fact that we were able to replicate a previous study, and the fact that there is internal consistency in both referent conditions (osteoporosis and cancer), raise our confidence about the results and the conclusions of our study. However, carefully controlled clinical studies are required to

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  • Cited by (0)

    This research was partially supported by National Institute of Dental and Craniofacial Research grant 1 R21 DE018143-01.

    1

    Dr. Cartsos is an assistant professor, Department of Orthodontics, School of Dental Medicine, Tufts University, Boston.

    2

    Dr. Zhu is a medical analyst, Ingenix—i3 Drug Safety, Basking Ridge, N.J.

    3

    Dr. Zavras is an associate professor and the director of dental public health, Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, 188 Longwood Ave., REB217, Boston, Mass. 02115, e-mail “[email protected]”. Address reprint requests to Dr. Zavras.

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