Longitudinal Cohort Study of Risk Factors in Cancer Patients of Bisphosphonate-Related Osteonecrosis of the Jaw
ABSTRACT 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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ABSTRACT: Osteonecrosis of the jaw (ONJ) is a chronic complication affecting long-term bisphosphonate-treated subjects, recognized by non-healing exposed bone in the maxillofacial region. The pathophysiological mechanism underlying ONJ has not been fully elucidated. The aim of the present study was to investigate the role of RANK/RANKL/OPG signaling pathway and, in parallel, to evaluate angiogenic and matrix mineralization processes in jaw bone necrotic samples obtained from bisphosphonate-treated subjects with established ONJ. Necrotic bone samples and native bone samples were processed for Light and Field Emission in Lens Scanning Electron Microscope (FEISEM) analyses, for Real-Time RT-PCR to evaluate the gene expression of TNFRSF11A (RANK), TNFSF11 (RANKL), and TNFSF11B (OPG) and for immunohistochemical analyses of VEGF and BSP expression. Morphological analyses performed by Light microscope and FEISEM show empty osteocytic lacunae and alteration of lamellar organization with degradation of the mineralized bone matrix in necrotic bone samples. A significant increase in TNFRSF11A, TNFSF11, TRAF6 and NFAT2 gene expression, and a reduction of TNFSF11B gene transcription level compared is also showed in necrotic bone compared to control samples. No significant difference of VEGF expression is evidenced, while lower BSP expression in necrotic bone compared to healthy samples is found. Even if the pathogenesis of bisphosphonate-associated ONJ remains unknown, a link between oral pathogens and its development seems to exist. We suppose lipopolysaccharide produced by bacteria colonizing and infecting necrotic bone and the surrounding viable area could trigger RANK/RANKL/OPG signaling pathway and, in this context, osteoclasts activation could be considered as a protective strategy carried out by the host bone tissue to delimitate the necrotic area and to counteract infection.European journal of histochemistry: EJH 02/2015; 59(1). DOI:10.4081/ejh.2015.2455 · 2.24 Impact Factor
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ABSTRACT: Medication-related osteonecrosis of the jaw (ONJ) is often preceded by dentoalveolar trauma. The aim of this study was to examine the frequency of dentoalveolar trauma precipitated ONJ and compare trauma-precipitated ONJ with spontaneously developing ONJ. This was a retrospective study. All patients were examined according to a standard ONJ chart. Among 149 consecutive ONJ patients from the Copenhagen Cohort, 95 (64%) had a dentoalveolar trauma before referral (trauma group): dental extractions (n = 80); denture-related sore mouth (n = 12); and others (n = 3). The remaining 54 patients had spontaneous ONJ (spontaneous group). The mean time from oral trauma to referral for ONJ was 8 months. This study documented that dentoalveolar trauma precipitated ONJ in the majority of cases. However, even minor trauma, such as intubation and impression tray lesions, precipitated ONJ in a few cases (1%). Besides the occurrence of fistula to the skin and a difference in the male-to-female ratio, we found no significant difference between the spontaneous and trauma groups. Copyright © 2015 Elsevier Inc. All rights reserved.Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 01/2015; DOI:10.1016/j.oooo.2014.12.024 · 1.46 Impact Factor
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ABSTRACT: Osteonecrosis of the jaw (ONJ) is a severe side effect associated with antiresorptive treatment. Monitoring of ONJ using routine databases in Scandinavian countries is a challenge owing to lack of valid algorithms and to heterogeneous referral practices. The aim of this paper is to describe the process of establishing a Scandinavian ONJ Cohort enrolling all ONJ cases related to antiresorptive treatment arising in Denmark, Norway, and Sweden between 2011 and 2019. The initial purpose of the cohort is to support an ongoing pharmacovigilance study of denosumab and zoledronic acid in Denmark, Norway, and Sweden. The three countries, with their 199 clinics, departments, and units of oral and maxillofacial surgery, both hospital-based and freestanding, differ somewhat in referral practices of the ONJ patients. By directly contacting all providers of care to ONJ patients in the three countries, we established a network for reporting incident cases to each country's research database directly or through a member of the Scandinavian ONJ task force as a liaison. The task force includes a Scandinavian coordinator and three national coordinators collaborating directly with the clinics. A uniform ONJ registration form has been developed, and the relevant medical community has been informed either directly or through presentations at professional meetings. A website with study information is published in each country, and data entry is ongoing. This large-scale systematic uniform registration of ONJ cases in Denmark, Norway, and Sweden, with an underlying total population of more than 20 million people, merged into the Scandinavian ONJ Cohort, will contribute to better knowledge and understanding of this challenging group of patients, and ultimately, help improve patient care. The Scandinavian ONJ Cohort as a whole and its component national ONJ research databases may offer the potential for large-scale multinational intervention and safety studies in the future.Clinical Epidemiology 01/2015; 7:107-16. DOI:10.2147/CLEP.S71796