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Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents

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Abstract

Introduction

The incidence rate and risk factors of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate cancer patients with bone metastasis are not clear.

Materials and Methods

We retrospectively reviewed patients’ records of prostate cancer patients with bone metastasis who were treated with zoledronic acid or denosumab between 1/Dec/2008 and 31/Mar/2019. ARONJ-free survival rate was analyzed with Kaplan–Meier analysis, and risk factors for ARONJ were analyzed with Cox proportional hazard model.

Results

We identified 124 and 67 patients treated with zoledronic acid and denosumab, respectively. Seventy-six patients were hormone sensitive, and 115 patients were castration resistant when they started bone-modifying agents (BMA). Twenty-eight patients developed ARONJ during the observation period (median: 23 months, range 1–130 months). Their number of doses of BMA ranged 3–69 (median: 21.5). The 2-year ARONJ-free survival rate was 91.1%, and the 5-year ARONJ-free survival rate was 72.5%. There was no significant difference in the incidence rate of ARONJ between zoledronic acid and denosumab. However, multivariate analysis revealed that use of denosumab (hazard ratio [HR] 3.67, 95% confidence interval [CI] 1.01–13.31; p = 0.0484), serum calcium < 9.2 mg/dL (HR 3.16, 95% CI 1.10–9.13; p = 0.033)), and concomitant or prior use of chemotherapeutic agents (HR 4.71, 95% CI 1.51–14.71; p = 0.0076) were independent risk factors for the development of ARONJ.

Conclusion

Almost one-quarter of patients had a risk of developing ARONJ within 5 years after starting BMA. Low serum calcium, use of chemotherapeutic agents, and use of denosumab might contribute to the development of ARONJ.

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Abbreviations

ADT:

Androgen-deprivation therapy

ARONJ:

Antiresorptive agent-related osteonecrosis of the jaw

BMA:

Bone-modifying agent

CI:

Confidence interval

CRPC:

Castration-resistant prostate cancer

HR:

Hazard ratio

ONJ:

Osteonecrosis of the jaw

SRE:

Skeletal-related event

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Urology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan

    Yasutomo Nakai, Tomohiro Kanaki, Akinaru Yamamoto, Ryo Tanaka, Yoshiyuki Yamamoto, Akira Nagahara, Masashi Nakayama, Ken-ichi Kakimoto & Kazuo Nishimura

  2. Department of Dentistry, Osaka International Cancer Institute, Osaka, Japan

    Miki Ishibashi

Authors
  1. Yasutomo Nakai
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  2. Tomohiro Kanaki
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  3. Akinaru Yamamoto
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  6. Akira Nagahara
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  8. Ken-ichi Kakimoto
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Contributions

YN, TK, AY, RT, YY, AN, MN, KK and KN collected patients’ clinical data. MI reviewed the oral health status of the patients. YN performed statistical analysis and was a major contributor in writing the manuscript. KN reviewed all of the data presented in this report. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kazuo Nishimura.

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Conflict of interest

K.N. received speaker honoraria from Astellas and Novartis; consulting fee from Astellas, AstraZeneca and Janssen; research funding from Bayer outside the submitted work. The remaining authors declare that they have no conflict of interest.

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Nakai, Y., Kanaki, T., Yamamoto, A. et al. Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents. J Bone Miner Metab 39, 295–301 (2021). https://doi.org/10.1007/s00774-020-01151-9

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  • DOI: https://doi.org/10.1007/s00774-020-01151-9

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