Osteonecrosis of the jaw and bisphosphonates

The recent editorial by Landis et al has added confusion rather than clarity to the issue of osteonecrosis of the jaw (ONJ) in association with the use of bisphosphonates.¹ They do not distinguish between the use of very high doses of intravenous bisphosphonates (monthly pamidronate or zoledronate) to treat patients with malignancy, and the use of much lower doses of bisphosphonates (approximately 1/12 of the oncology dose) in the treatment of Paget's disease or osteoporosis. These two different uses of bisphosphonates have been associated with different risks for ONJ. The authors quote an incidence of 1-10% for ONJ in association with bisphosphonates.¹ However, they fail to indicate that this estimate relates to people with malignancy treated with high dose intravenous bisphosphonates. They also refer to ONJ as “avascular osteonecrosis of the jaw”.¹ ONJ is not usually termed “avascular” since reduced vascularity has not been proved to be an aetiological factor in ONJ associated with bisphosphonate treatment.

Most patients who receive bisphosphonates are prescribed them for osteoporosis or Paget's disease. By March 2006, about 170 cases worldwide of ONJ in association with alendronate had been reported to the manufacturer (Merck).² There are few clinical details available for most of these cases. In 2004, it was estimated that there had been about 20 million patient-years of alendronate treatment for osteoporosis or Paget's disease.³ While it is possible that under-reporting of cases of ONJ has occurred, this would have to be very substantial to significantly alter the very low incidence. No cases of ONJ were reported in randomised controlled trials of alendronate, risedronate, zoledronate, and ibandronate in non-malignant skeletal disease that collectively included more than 60 000 patients treated for at least two years.⁴ In the recently completed three year trial of annual zoledronate in >7000 postmenopausal women with osteoporosis, there was one case of ONJ in the zoledronate group, and one in the placebo group--interestingly the latter patient had never received any bisphosphonate treatment.⁵ Therefore, while the incidence of ONJ in patients treated with bisphosphonate for Paget's disease and osteoporosis is difficult to determine, it is very likely to be less than one in 60 000.

The authors recommend that all people have a specialist dental review before starting bisphosphonate treatment,¹ in agreement with other dental authorities, even though they acknowledge that this approach has not been proved to prevent ONJ. For patients with osteoporosis and Paget's disease, who appear to have an extremely low risk of ONJ, this intervention (even if it was 100% effective) is not likely to be cost effective, and may lead to unnecessary invasive dental procedures, with attendant morbidity.