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01-05-2021 | Denture | Original Article

Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307)

Authors: Darya A. Kizub, Jieling Miao, Mark M. Schubert, Alexander H. G. Paterson, Mark Clemons, Elizabeth C. Dees, James N. Ingle, Carla I. Falkson, William E. Barlow, Gabriel N. Hortobagyi, Julie R. Gralow

Published in: Supportive Care in Cancer | Issue 5/2021

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.

Clinical trial number

NCT00127205

Registration date

July 2005

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Title: Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307)
Authors: Darya A. Kizub
Jieling Miao
Mark M. Schubert
Alexander H. G. Paterson
Mark Clemons
Elizabeth C. Dees
James N. Ingle
Carla I. Falkson
William E. Barlow
Gabriel N. Hortobagyi
Julie R. Gralow
Publication date: 01-05-2021
Publisher: Springer Berlin Heidelberg
Keywords: Denture
Bisphosphonate
Breast Cancer
Osteonecrosis
Breast Cancer
Gingival Diseases
Zoledronic Acid
Ibandronate
Published in: Supportive Care in Cancer / Issue 5/2021
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-020-05748-8

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