Pathology
Oral Bisphosphonate Use Increases the Risk for Inflammatory Jaw Disease: A Cohort Study

https://doi.org/10.1016/j.joms.2011.02.093Get rights and content

Purpose

The objective of this study was to address whether among people living in Denmark, those treated with medications to prevent osteoporosis have an increased risk for inflammatory jaw disease compared with those not treated.

Patients and Methods

A historical cohort study was designed to compare the rate of inflammatory jaw-related events, ie, osteomyelitis, osteitis, periostitis, or sequestrum, between Danish patients who had been prescribed oral bisphosphonates (BP) and other drugs for the treatment of osteoporosis between 1996 and 2006 (the exposed group), and a random sample of the Danish population drawn from a nationwide registry who had not been prescribed oral BPs or other medications to treat osteoporosis (the nonexposed group). The nonexposed subjects were age- and gender-matched to the exposed subjects and randomly drawn from the general population at a ratio of 3 non-BP subjects to 1 BP subject. The primary explanatory variable was oral BP exposure status. Associations between BP treatment and inflammatory jaw events were ascertained using hazard ratios (HR) Cox proportional hazards models.

Results

The study sample was composed of 103,562 index subjects and 310,683 control subjects. After adjusting for other factors, including diabetes and chemotherapy, alendronate (HR = 3.15, 95% confidence interval 1.44-6.87) and etidronate (HR = 2.23, 95% confidence interval 1.15-4.31) were associated with an increased risk for inflammatory jaw events. There was no association between oral BP dose and risk for inflammatory jaw events.

Conclusion

The oral BPs alendronate and etidronate were associated with an increased risk for inflammatory jaw events.

Section snippets

Study Design

A historical cohort design was chosen with patients using drugs, particularly oral bisphosphonates, for the treatment or prevention of osteoporosis categorized as index subjects (exposed group). Control subjects (nonexposed group) were individuals who had not taken any drugs for the treatment or prevention of osteoporosis. The definition of nonexposed reduced the potential bias from control subjects having been treated with drugs, such as strontium ranelate or raloxifene, for osteoporosis.

Sample

The

Results

In the exposed group, the number of users of bisphosphonates other than alendronate and etidronate was small. Nonbisphosphonates, raloxifene, strontium ranelate, and parathyroid hormone and analogues were prescribed infrequently (Table 1). The exposed and nonexposed were well matched for age and gender. The exposed had a higher prevalence of diabetes, Sjögren's syndrome, and alcoholism both before and after starting the drugs in question. The exposed also had more often received chemotherapy or

Discussion

The findings of this study indicate an increased risk of jaw-related events in users of alendronate and etidronate even after adjustment for radiation therapy, chemotherapy, and diabetes. For the other drugs recorded, no inflammatory jaw events were observed, although the introduction of some of these drugs for treatment or prevention of osteoporosis is relatively recent, and the number of individuals prescribed other drugs was small. No dose–response relationship was present for alendronate or

Acknowledgments

This study was funded by an unrestricted grant from Servier, Denmark, and the Dandy Foundation. None of the sponsors had any role in obtaining or analyzing data or writing the report.

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