2009; Volume 10, No 5, May



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Article of the Month

Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan.

Ripamonti CI, Maniezzo M, Campa T et al.

Annals of Oncology 2009; 20: 137-145

During the past years, osteonecrosis of the jaw (ONJ) emerged as a serious and uncomfortable complication in cancer patients receiving bisphosphonates (BPs) for bone metastases or osteoporosis.

Major risk factors for ONJ are 1) tooth extractions (about 60%), 2) major dental surgery during the course of BP therapy, 3) duration of administration of BP therapy and 4) the type of BP administered. The role of the concomitant use of steroids and antiangiogenic drugs, poor oral hygiene, diabetes and peripheral vasculopathy all need further investigation.

Published recommendations for screening of the oral cavity include

  • careful visual examination,

  • dental care - proactive management of any possible dental disorders before starting BP therapy, and

  • the use of antibiotics,

All were suggested as mandatory preventive measures for preventing ONJ in patients before receiving BPs.

We compared a retrospective group (PRE- group) of 812 patients (median age 62.4) treated with BPs who did not receive any preventive dental care with a prospective group (POST-group) of 154 patients (median age 62.9) who were included in the dental preventive programme. The aim of the study was to verify if the application of preventive measures could clinically reduce the incidence of ONJ.

The study included all 966 patients treated from 1 January 1999 to 28 February 2007 (73% of the patients had breast cancer) with at least one intravenous infusion of pamidronate, or zoledronic acid, or pamidronate followed by zoledronic acid, or clodronate (only for patients with osteoporosis). Twenty-eight patients developed ONJ. In the PRE – and POST- Groups the median follow-up time was 9.3 and 11.4 months, respectively.

There was an incidence reduction of ONJ from 3.2% to 1.3 % when one compares the pre and post-implementation of a preventive measure programme. In the POST- Group two patients treated with zoledronic acid developed ONJ after undergoing a dental avulsion before BP treatment. One patient developed ONJ in spite of an antibiotic therapy and it was assumed that this patient followed the prescribed doses before and after dental avulsion, while the other patient did not follow the prescribed antibiotic advice.

The incidence rate of ONJ was 2.9% in PRE-Group and 1.4% in POST-Group according to the intention - to - treat analysis of all patients treated with any BP. If we consider the per-protocol analysis, excluding the patient in the POST-Group who underwent a dental avulsion before starting BP treatment, but refused to take antibiotics, the incidence rate becomes 3.0% in PRE-Group and 0.7% in the POST-Group, i.e., a significant decrease. This confirms the guidelines previously published on ONJ prevention.

Why I choose this article

Bone metastases are the most common event in cancer patients that produce complications such as pain, hypercalcemia, and increased risk of skeletal-related events (SREs) that significantly influence the clinical course of the disease.

Intravenous BPs such as pamidronate, ibandronate, zoledronate have been shown to significantly reduce SREs, pain and hypercalcemia both in solid tumors related bone metastases as well as in hematological malignancies such as multiple myeloma.

BPs have changed the clinical history of bone metastases. ONJ, which is the most feared side-effect of the BPs, can be prevented by means of adequate dental care before the administration of BPs.

Dr. Ripamonti is a medical oncologist and member of the Board of Directors of IAHPC. To view her biography please go to: http://www.hospicecare.com/Bio/c_ripamonti.htm

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