Bisphosphonate-induced osteonecrosis of the jaw (ONJ): Incidence and risk factors in patients with breast cancer and gynecological malignancies

1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.

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Bisphosphonate-induced osteonecrosis of the jaw (ONJ): Incidence and risk factors in patients with breast cancer and gynecological malignancies

Breast Diseases A Year Book Quarterly ◽

10.1016/s1043-321x(09)79447-0 ◽

2009 ◽

Vol 20 (4) ◽

pp. 431-432

Author(s):

C.L. Shapiro

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Osteonecrosis Of The Jaw ◽

Gynecological Malignancies

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Incidence of and risk factors for medication-related osteonecrosis of the jaw in women with breast cancer with bone metastasis: a population-based study

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2020.04.808 ◽

2020 ◽

Vol 130 (3) ◽

pp. 252-257

Author(s):

Fredrik Hallmer ◽

Olof Bjarnadottir ◽

Bengt Götrick ◽

Per Malmström ◽

Gunilla Andersson

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Bone Metastasis ◽

Population Based ◽

Osteonecrosis Of The Jaw ◽

Population Based Study

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Second primary gynecologic neoplasms among breast cancer survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1588 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1588-1588

Author(s):

Maria Pilar Barretina Ginesta ◽

Miguel Beltran ◽

Maria Buxo ◽

Nuria Sala ◽

Neus Baste ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

General Population ◽

Gynecological Cancer ◽

Second Primary ◽

Endometrioid Adenocarcinoma ◽

Type I ◽

Cancer Susceptibility Genes ◽

Gynecological Malignancies ◽

Shared Risk

1588 Background: Excess of risk of several second primary malignancies after treatment for breast cancer (BC) has been reported. This risk can be related with shared risk factors, cancer susceptibility genes or prior treatments received. Hormonal factors and hormone therapy are known to be risk factors for both BC and some gynecological malignancies. The aim of this study was to asses gynecological cancer risk as a second neoplasm among BC patients in our population. Methods: Patients diagnosed with invasive BC (CIE10: C50.0-C50.9) and registered in the Girona Cancer Registry from 1980 to 2006 were included in our study. We analyzed their incidence of second gynaecological malignancies except for contralateral BC. Standardized Incidence Ratios (SIR) and absolute excess of risk (AER) of these patients compared to general population were calculated. Results: 6.209 patients were diagnosed of invasive BC in this period, with median age at diagnosis 62 years, median follow-up 4 years. 84 of them developed a second malignancy of gynaecological origin (SIR 1,98 CI 95% 1,59-2,44; AER 104,01/100.000 person-year). We observed 4 uterine cervix (SIR 0.64 IC95% 0,20-1,54), 3 vulvar-vaginal (SIR 0,96 IC95% 0,24-2,60), 13 ovarian (SIR 1,13 IC95% 0,63-1,89) and 63 uterine corpus neoplasms (UC), as well as 1 genital female tract neoplasm unspecified. High and statistically significant SIR was observed for gynecological malignancies in general and specifically for UC(SIR 3.14 IC 95% 2,44-4,00). With this finding, histology of UC cases was reviewed. 12 out of 63 were malignant histologies, not otherwise specified. Among the remaining 51, there were 8 type II (1 clear cell and 7 serous adenocarcinoma, 15.7%), 34 type I (endometrioid adenocarcinoma, 66.7%) and 6 carcinosarcomas (11.8%). There were also 2 adenosarcomas (3.9%) and 1 mucinous adenocarcinoma (1.9%). Conclusions: Women with previous BC have an elevated risk of developing a second primary gynecological malignancy compared with general population, particularly for UC. These patients should be followed up for its early detection. We detected a slight increase in unfavourable uterine carcinoma histologies respect to the general population. Further investigation of this finding is warranted.

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Prevalence and risk factors of medication-related osteonecrosis of the jaw in osteoporotic and breast cancer patients: a cross-sectional study

Supportive Care in Cancer ◽

10.1007/s00520-019-05044-0 ◽

2019 ◽

Vol 28 (5) ◽

pp. 2265-2271 ◽

Cited By ~ 2

Author(s):

Ana Laura Soares ◽

Sérgio Simon ◽

Luiz Henrique Gebrim ◽

Afonso Celso P. Nazário ◽

Marise Lazaretti-Castro

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Cancer Patients ◽

Cross Sectional Study ◽

Osteonecrosis Of The Jaw ◽

Breast Cancer Patients ◽

Sectional Study ◽

Cross Sectional

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

Journal of Clinical Oncology ◽

10.1200/jco.2009.21.9584 ◽

2009 ◽

Vol 27 (32) ◽

pp. 5356-5362 ◽

Cited By ~ 257

Author(s):

Konstantinos Vahtsevanos ◽

Athanassios Kyrgidis ◽

Evgenia Verrou ◽

Eirini Katodritou ◽

Stefanos Triaridis ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Cohort Study ◽

Smoking Status ◽

Underlying Disease ◽

Osteonecrosis Of The Jaw ◽

Relative Risks ◽

Increased Risk ◽

Increase Risk ◽

History Of

Purpose 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. Patients and Methods 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. Results 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. Conclusion 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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