Bisphosphonates,  Dentistry,  Osteonecrosis

Osteonecrosis of the Jaw Associated With Bisphosphonate Agent Zoledronic Acid and Chemotherapy Combined With the Antiangiogenic Agent Bevacizumab

Osteonecrosis of the Jaw (ONJ)

This study has just appeared in the Journal of the American Dental Association. Here is the abstract.

Background. The authors investigated the incidence of and risk factors for osteonecrosis of the jaw (ONJ) in patients with metastases to the bone who received the bisphosphonate agent zoledronic acid (ZOL) and chemotherapy combined with the antiangiogenic agent bevacizumab (BEV).

Methods. The authors evaluated 59 participants (34 with breast cancer and 25 with nonsmall-cell lung cancer). All of the participants received 4 milligrams of ZOL via intravenous (IV) infusion every four weeks and 15 mg per kilogram of BEV every three weeks. They conducted a dental examination in participants at baseline and every three months until the patients died or were lost to follow-up. If needed, participants received periodontal disease treatment and underwent tooth extraction before they started receiving ZOL and BEV.

Results. The median time the participants received ZOL therapy was 18.8 months (range, 3.1–28.9 months); 36 participants (61.0 percent) received ZOL therapy for more than one year. The median time participants received BEV therapy was 16.7 months (range, 2.8–29.6 months). None of the participants required dentoalveolar surgery while undergoing cancer treatment. After a median follow-up period of 19.7 months, none of the participants developed bisphosphonate-related ONJ.

Conclusions and Clinical Implications.
ZOL combined with BEV did not predispose to ONJ participants with cancer that had metastasized to the bone who underwent a baseline dental examination and preventive dental measures. The study results must be considered in the context of the study’s protocols and the follow-up period.

So, the question is whether these patients were prevented from developing osteonecrosis of the jaw (ONJ) because of the drug therapy or because of dental treatment protocols?

The researchers took several measures to reduce the study participants’ risk of developing ONJ, including the following:

  • Dental caries and periodontal disease were treated before starting study treatment.
  • Mouth rinses with chlorhexidine and local antibiotic agents were administered before baseline oral hygiene.
  • Recommendations were made for maintaining good oral hygiene.
  • Teeth were extracted at least four weeks before starting ZOL and BEV therapy.
  • Invasive dental procedures were avoided during treatment.
  • If invasive dental procedures were needed during treatment, ZOL and BEV were readministered after at least four weeks.

All the patients received a dental exam and panoramic x-rays before starting treatment and every three months until the patients died or were lost to follow-up. After a median follow-up period of 19 months, none of the study participants had developed ONJ.

So, antiangiogenesis or treating the patient dentally prior to IV ZOL treatment?

The jury continues to be out.

But, preventive dental measures, including baseline dental examinations and follow-up are simple to institute and probably prudent, in any case.

“Although further research is needed, the results of our study suggest that ZOL combined with the antiangiogenic agent BEV does not predispose patients with metastases to the bone from breast and NSCL cancer to ONJ if they undergo a baseline dental examination,” they concluded. “Nevertheless, the results of the study must be considered in the context of the follow-up period used in the study and the use of the preventive dental protocol.”

Tanja Fehm, MD, from the department of obstetrics and gynecology at the University of Tübingen in Germany, has done similar research (Gynecologic Oncology, March 2009, Vol. 112:3, pp. 605-609). She told that the incidence of ONJ is low — between 1% and 4% — in metastatic breast cancer patients receiving bisphosphonates.

“Therefore, the number of patients (59) investigated in this study is too low to make meaningful conclusions,” she added. “However, the paper summarizes the preventive measures that can help avoid ONJ.”


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