Longitudinal Cohort Study of Risk Factors in Cancer Patients of Bisphosphonate-Related Osteonecrosis of the Jaw

Aristotle University of Thessaloniki, Saloníki, Central Macedonia, Greece
Journal of Clinical Oncology (Impact Factor: 18.43). 10/2009; 27(32):5356-62. DOI: 10.1200/JCO.2009.21.9584
Source: PubMed


The reported incidence of osteonecrosis of the jaw (ONJ) ranges from 0.94% to 18.6%. This cohort study aimed to calculate the incidence of and identify the risk factors for ONJ in patients with cancer treated with intravenous zoledronate, ibandronate, and pamidronate.
Data analyzed included age, sex, smoking status, underlying disease, medical and dental history, bisphosphonates (BP) type, and doses administered. Relative risks, crude and adjusted odds ratios (aORs), and cumulative hazard ratios for ONJ development were calculated.
We included 1,621 patients who received 29,006 intravenous doses of BP, given monthly. Crude ONJ incidence was 8.5%, 3.1%, and 4.9% in patients with multiple myeloma, breast cancer, and prostate cancer, respectively. Patients with breast cancer demonstrated a reduced risk for ONJ development, which turned out to be nonsignificant after adjustment for other variables. Multivariate analysis demonstrated that use of dentures (aOR = 2.02; 95% CI, 1.03 to 3.96), history of dental extraction (aOR = 32.97; 95% CI, 18.02 to 60.31), having ever received zoledronate (aOR = 28.09; 95% CI, 5.74 to 137.43), and each zoledronate dose (aOR = 2.02; 95% CI, 1.15 to 3.56) were associated with increased risk for ONJ development. Smoking, periodontitis, and root canal treatment did not increase risk for ONJ in patients receiving BP.
The conclusions of this study validated dental extractions and use of dentures as risk factors for ONJ development. Ibandronate and pamidronate at the dosages and frequency used in this study seem to exhibit a safer drug profile concerning ONJ complication; however, randomized controlled trials are needed to validate these results. Before initiation of a bisphosphonate, patients should have a comprehensive dental examination. Patients with a challenging dental situation should have dental care attended to before initiation of these drugs.

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Available from: Kyriaki Kitikidou, Nov 11, 2015
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    • "In patients treated with oral or intravenous BPs, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been and continues to be reported as a relatively rare, but potentially severe complication. It is characterized clinically as an area of exposed bone in the maxilla or the mandible that has failed to heal within a period of six to eight weeks in a patient currently or previously exposed to N-BPs who has not undergone radiation therapy in craniofacial region [6–8]. BRONJ progression is three-staged, which are identified based on clinical signs and symptoms. "
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    ABSTRACT: Bisphosphonates (BPs) are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as "an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region." Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS) considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.
    Full-text · Article · Apr 2014 · International Journal of Dentistry
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    • "There is a considerable discussion in the literature whether aging plays a significant role in BRONJ development. Some studies found no statistically significant correlation between aging and BRONJ [30,31]. Therefore, the advanced age of the patients with BRONJ observed in the studies [6,8,10-12,14-16,18-21] may reflect nothing less than the increased BPs prescription to older patients compared with younger ones, since osteoporosis and RA are commonly seen in the elderly [29,32]. "
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    ABSTRACT: This literature review aims to evaluate the epidemiologic profile of patients with rheumatoid arthritis (RA) that developed a bisphosphonate-related osteonecrosis that affect the jaws (BRONJ), including demographic aspects, as well as clinical and therapeutic issues. A search of PUBMED/MEDLINE, Scopus, and Cochrane databases from January 2003 to September 2011 was conducted with the objective of identifying publications that contained case reports regarding oral BRONJ in RA patients. Patients with RA who develop oral BRONJ are usually women above 60 years taking steroids and long-term alendronate. Most of them have osteoporosis, and lesions, triggered by dental procedures, are usually detected at stage II in the mandible. Although there is no accepted treatment protocol, these patients seem to have better outcomes with conservative approaches that include antibiotic therapy, chlorhexidine, and drug discontinuation.
    Full-text · Article · Mar 2012 · Head & Face Medicine
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    • "Majority of the reported cases of bisphosphonate induced ONJ were found in patients older than 60 years of age (Hong et al., 2010; Kicken et al., 2007). Additionally, the majority of the ONJ cases were associated with intravenous bisphosphonates, or with long usage of bisphosphonates with other treatment modalities such as: chemotherapy, steroids intake , or radiotherapy (Vahtsevanos et al., 2009; Lodi et al., 2010; Statz et al., 2007). Generally, Patients receiving oral bisphosphonates like alendronate have lower risk than patients with high potent bisphosphonates for cancer treatment pamidronate and zoledronic acid. "
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    ABSTRACT: The objective of this study is to obtain data on the prevalence of bisphosphonate-associated osteonecrosis of the jaws (ONJ) among patients who received dental treatment in Riyadh.The study was conducted in five hospitals in the Riyadh area. All subjects were interviewed to collect data regarding their medical history, bisphosphonates usage, dental history, and possible complications after dental treatment. A total of 88 subjects under bisphosphonates therapy were interviewed, 25% were males and 75% were females. Bisphosphonates were taken orally by 89.7% of the subjects while 10.2% received bisphosphonate intravenously. All the subjects have had dental treatments after the beginning of bisphosphonate therapy. 79.5% of those patients had dental extraction, 13.6% root canal treatment, 4.5% oral surgery, and 4.5% received dental implants. No complications were reported after the dental treatment.In the present study, patients with bisphosphonates therapy did not develop complication after the dental treatment. However, it is recommended that patients receiving bisphosphonate therapy should be treated with precaution. Dental awareness programs should be provided to the physicians prescribing bisphosphonates to their patients.
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