Database Analysis of the Risk Factors of Bisphosphonate-related Osteonecrosis of the Jaw in Hungarian Patients

Overview

Journal BMJ Open

Specialty General Medicine

Date 2019 May 25

PMID 31122970

Citations 9

Authors

Edit Veszelyne Kotan

Timea Bartha-Lieb

Zsolt Parisek

Attilane Mesko

Mihaly Vaszilko

Balazs Hanko

Affiliations

Soon will be listed here.

Abstract

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but serious side effect of bisphosphonates (BPs). Since this disease has no independent code in either of the diseases' or in the medical procedures' classifications, it is hard to estimate how many BP patients are affected.

Design: A retrospective observational epidemiological registry-based study was carried out, using the data of the national service of Hungary on the incidence of BRONJ and related factors.

Setting: A data analysis was performed, which is relevant for the whole Hungarian population from 2010 to 2014. The socioeconomic and medication data of 236 207 BP patients were analysed, and a method was worked out to define BRONJ patients from the Hungarian BP population.

Primary And Secondary Outcome Measures: The incidences of BRONJ were analysed according to genders and the types of the BP drugs administered. The marginal interdependence between the types of BP drugs, modes of administration and main indication was calculated.

Results: 340 BP patients (0.1%) developed BRONJ. The incidence of BRONJ in Hungary in the malignant indication of BPs is 0.9%, and 0.1% in the non-malignant indication, and the OR to develop BRONJ was OR=9.7 (95% CI 7.8 to 12.1) between them. Although more women developed BRONJ, the proportion of men was significantly higher than that of women. Steroids increase the risk of jaw osteonecrosis, and differences were also found between the BP drugs.

Conclusions: Oncology indicated, intravenously administered and steroid comedicated BP therapies pose a high risk of developing BRONJ in the Hungarian population.

Citing Articles

The Microbiological Background of Medication-Related Osteonecrosis of the Jaw (MRONJ): Clinical Evidence Based on Traditional Culture and Molecular Biological Detection Methods.

Kover Z, Gajdacs M, Polgar B, Szabo D, Urban E Antibiotics (Basel). 2025; 14(2).

PMID: 40001446 PMC: 11851722. DOI: 10.3390/antibiotics14020203.

A Multi-Center Observation Study on Medication-Related Osteonecrosis of the Jaw (MRONJ) in Patients with Osteoporosis, and Other Non-Malignant Bone Diseases, in Northwestern Italy over 16 Years.

Karimi D, Arduino P, Gambino A, Erovigni F, DellAcqua A, Pera F Biomedicines. 2024; 12(10).

PMID: 39457492 PMC: 11505559. DOI: 10.3390/biomedicines12102179.

Role of Actinomyces spp. and related organisms in the development of medication-related osteonecrosis of the jaw (MRONJ): Clinical evidence based on a case series.

Kover Z, Ban A, Gajdacs M, Polgar B, Urban E Eur J Microbiol Immunol (Bp). 2023; 13(4):125-134.

PMID: 38038751 PMC: 10755666. DOI: 10.1556/1886.2023.00041.

Risk Factors for Bisphosphonate-Related Osteonecrosis of the Jaws in Bone Metastatic Breast and Prostate Cancer under Zoledronate Treatment: A Retrospective Analysis from 10 Years of Evaluation.

Carlos A, Coelho L, Nobrega Malta C, Magalhaes I, Borges M, Erialdo da Silva Junior J Asian Pac J Cancer Prev. 2023; 24(8):2681-2689.

PMID: 37642054 PMC: 10685221. DOI: 10.31557/APJCP.2023.24.8.2681.

Risk Factors for Medication-Related Osteonecrosis of the Jaw-A Binomial Analysis of Data of Cancer Patients from Craiova and Constanta Treated with Zoledronic Acid.

Ciobanu G, Camen A, Ionescu M, Vlad D, Munteanu C, Gheorghita M J Clin Med. 2023; 12(11).

PMID: 37297941 PMC: 10253558. DOI: 10.3390/jcm12113747.

References

Guarneri V, Miles D, Robert N, Dieras V, Glaspy J, Smith I . Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. Breast Cancer Res Treat. 2010; 122(1):181-8. DOI: 10.1007/s10549-010-0866-3. View

McCloskey E, Dunn J, Kanis J, MacLennan I, Drayson M . Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma. Br J Haematol. 2001; 113(4):1035-43. DOI: 10.1046/j.1365-2141.2001.02851.x. View

Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C, Boukovinas I, Teleioudis Z . Bisphosphonate-related osteonecrosis of the jaws: a case-control study of risk factors in breast cancer patients. J Clin Oncol. 2008; 26(28):4634-8. DOI: 10.1200/JCO.2008.16.2768. View

Saad F, Brown J, Van Poznak C, Ibrahim T, Stemmer S, Stopeck A . Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2011; 23(5):1341-1347. DOI: 10.1093/annonc/mdr435. View

. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007; 65(3):369-76. DOI: 10.1016/j.joms.2006.11.003. View

Ruggiero S, Mehrotra B . Bisphosphonate-related osteonecrosis of the jaw: diagnosis, prevention, and management. Annu Rev Med. 2008; 60:85-96. DOI: 10.1146/annurev.med.60.063007.134350. View

Barasch A, Cunha-Cruz J, Curro F, Hujoel P, Sung A, Vena D . Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. J Dent Res. 2011; 90(4):439-44. PMC: 3144129. DOI: 10.1177/0022034510397196. View

Etminan M, Aminzadeh K, Matthew I, Brophy J . Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case-control study. J Rheumatol. 2008; 35(4):691-5. View

Ruggiero S, Dodson T, Fantasia J, Goodday R, Aghaloo T, Mehrotra B . American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014; 72(10):1938-56. DOI: 10.1016/j.joms.2014.04.031. View

10.

Veszelyne Kotan E, Meszaros A . [Therapeutic practice of bisphosphonate use and related pharmaceutical issues I]. Acta Pharm Hung. 2016; 86(1):13-22. View

11.

Ruggiero S, Mehrotra B, Rosenberg T, Engroff S . Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004; 62(5):527-34. DOI: 10.1016/j.joms.2004.02.004. View

12.

Khan A, Rios L, Sandor G, Khan N, Peters E, Rahman M . Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons. J Rheumatol. 2011; 38(7):1396-402. DOI: 10.3899/jrheum.100221. View

13.

Hong J, Nam W, Cha I, Chung S, Choi H, Kim K . Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia. Osteoporos Int. 2009; 21(5):847-53. DOI: 10.1007/s00198-009-1024-9. View

14.

Hoff A, Toth B, Altundag K, Johnson M, Warneke C, Hu M . Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008; 23(6):826-36. PMC: 2677083. DOI: 10.1359/jbmr.080205. View

15.

Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K . Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg. 2012; 41(11):1397-403. DOI: 10.1016/j.ijom.2012.06.020. View

16.

Black D, Delmas P, Eastell R, Reid I, Boonen S, Cauley J . Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007; 356(18):1809-22. DOI: 10.1056/NEJMoa067312. View

17.

Jadu F, Lee L, Pharoah M, Reece D, Wang L . A retrospective study assessing the incidence, risk factors and comorbidities of pamidronate-related necrosis of the jaws in multiple myeloma patients. Ann Oncol. 2007; 18(12):2015-9. DOI: 10.1093/annonc/mdm370. View

18.

Chiu C, Chiang W, Chuang C, Chang S . Resolution of oral bisphosphonate and steroid-related osteonecrosis of the jaw--a serial case analysis. J Oral Maxillofac Surg. 2010; 68(5):1055-63. DOI: 10.1016/j.joms.2009.12.030. View

19.

Marx R . Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003; 61(9):1115-7. DOI: 10.1016/s0278-2391(03)00720-1. View

20.

Wimalawansa S . Insight into bisphosphonate-associated osteomyelitis of the jaw: pathophysiology, mechanisms and clinical management. Expert Opin Drug Saf. 2008; 7(4):491-512. DOI: 10.1517/14740338.7.4.491. View