Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307)
- 14 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Supportive Care in Cancer
- Vol. 29 (5), 2509-2517
- https://doi.org/10.1007/s00520-020-05748-8
Abstract
Purpose Bisphosphonates reduce bone metastases in postmenopausal women with early-stage breast cancer but carry the risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We describe risk factors for BRONJ and compare BRONJ provoked by infection or trauma with spontaneous lesions, which carry a better prognosis. Methods SWOG 0307 randomized women with stage I-III breast cancer to receive zoledronic acid (ZA), clodronate (CL), or ibandronate (IB) for 3 years, implemented BRONJ prevention guidelines, and collected information about dental health and development of BRONJ. All statistical tests were two-sided. Results Of 6018 women, 48 developed BRONJ. Infection was present in 21 (43.8%). Median time to BRONJ was 2.1 years for ZA, 2.0 years for IB, and 3.4 years for clodronate (p= 0.04). BRONJ was associated with bisphosphonate type (28/2231 (1.26%) for ZA, 8/2235 (0.36%) for CL, 12/1552 (0.77%) for IB), dental calculus (OR 2.03), gingivitis (OR 2.11), moderate/severe periodontal disease (OR 2.87), and periodontitis > 4 mm (OR 2.20) (p< 0.05). Of 57 lesions, BRONJ occurred spontaneously in 20 (35.1%) and was provoked by dental extraction in 20 (35.1%), periodontal disease in 14 (24.6%), denture trauma in 6 (10.5%), and dental surgery in 2 (3.5%). Spontaneous BRONJ occurred more frequently at the mylohyoid ridge. There were no differences in dental disease, infection, or bisphosphonate type between spontaneous and provoked BRONJ. Conclusion ZA and worse dental health were associated with increased incidence of BRONJ, with a trend toward additive risk when combined. BRONJ incidence was lower than in similar studies, with prevention strategies likely linked to this. Registration date July 2005Keywords
Funding Information
- National Cancer Institute (NCI CA180888, CA180819, CA180820, CA180821, CA180868, CA180863)
- Susan G. Komen
- Breast Cancer Research Foundation
- Berlex
- Roche
- Genentech
- Novartis
This publication has 43 references indexed in Scilit:
- Metagenomic investigation of microbes and viruses in patients with jaw osteonecrosis associated with bisphosphonate therapyOral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2012
- Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trialThe Lancet Oncology, 2012
- A Role of Oral Bacteria in Bisphosphonate-induced Osteonecrosis of the JawJournal of Dental Research, 2011
- Osteonecrosis of the Jaw in Patients with Metastatic Breast Cancer: Ethnic and Socio-Economic AspectsThe Breast Journal, 2011
- Bisphosphonates' antitumor activity: An unravelled side of a multifaceted drug classBone, 2010
- Osteonecrosis of the jaw and use of bisphosphonates in adjuvant breast cancer treatment: a metanalysisBreast Cancer Research and Treatment, 2009
- Bisphosphonate‐related osteonecrosis of the jaw and its associated risk factors: A belgian case seriesThe Laryngoscope, 2009
- Bisphosphonate-induced osteonecrosis of the jaws: Prospective study of 80 patients with multiple myeloma and other malignanciesOral Oncology, 2008
- Osteonecrosis of the Maxilla and Mandible in Patients with Advanced Cancer Treated with Bisphosphonate TherapyThe Oncologist, 2008
- Bisphosphonates target multiple sites in both cis - and trans -prenyltransferasesProceedings of the National Academy of Sciences, 2007