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Article

Imbalance of Serum Bone-Metabolism-Related Factors Associated with Osteonecrosis of the Jaw

by
Kazuyuki Yusa
1,*,†,
Yuji Takeda
2,†,
Nobuyuki Sasahara
1,
Tomoharu Hemmi
1,
Shigeo Ishikawa
1 and
Tsuneo Konta
3
1
Department of Dentistry, Oral and Maxillofacial-Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
2
Department of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
3
Department of Public Health and Hygiene, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2025, 13(10), 2410; https://doi.org/10.3390/biomedicines13102410
Submission received: 2 September 2025 / Revised: 28 September 2025 / Accepted: 30 September 2025 / Published: 1 October 2025
(This article belongs to the Special Issue Biomedicine in Dental and Oral Rehabilitation)
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Abstract

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of bone-modifying agents. The aim of this study was to elucidate the pathogenesis of MRONJ through a comprehensive comparison of bone-metabolism-related factors in sera from patients with MRONJ and healthy controls. Methods: This study was a retrospective cross-sectional biobank analysis in which 31 patients in a non-MRONJ group and 10 patients in an MRONJ group were screened. Serum levels of 13 proteins (i.e., hormones, growth factors, and cytokines) related to bone metabolism were measured by simultaneous multi-parameter analysis using bead-based immunoassays. Results: The MRONJ group displayed suppressed bone metabolism with a background of chronic inflammation. In addition, a significant decrease in the expression of alkaline phosphatase liver/bone/kidney (p < 0.05, effect size of 0.46 (95% CI: 0.08 to 0.73)) and a significant increase (p < 0.05, effect size was −0.42 (95%CI: −0.72 to 0.01)) in the expression of tumor necrosis factor α were observed in the MRONJ group. Conclusions: These results may contribute to a better understanding of the etiology, pathophysiology, and progression of MRONJ.
Keywords: medication-related osteonecrosis of the jaw (MRONJ); diagnosis; bone metabolism; inflammation; bone-modifying agents (BMAs); bisphosphonates (BPs); denosumab (Dmab) medication-related osteonecrosis of the jaw (MRONJ); diagnosis; bone metabolism; inflammation; bone-modifying agents (BMAs); bisphosphonates (BPs); denosumab (Dmab)

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MDPI and ACS Style

Yusa, K.; Takeda, Y.; Sasahara, N.; Hemmi, T.; Ishikawa, S.; Konta, T. Imbalance of Serum Bone-Metabolism-Related Factors Associated with Osteonecrosis of the Jaw. Biomedicines 2025, 13, 2410. https://doi.org/10.3390/biomedicines13102410

AMA Style

Yusa K, Takeda Y, Sasahara N, Hemmi T, Ishikawa S, Konta T. Imbalance of Serum Bone-Metabolism-Related Factors Associated with Osteonecrosis of the Jaw. Biomedicines. 2025; 13(10):2410. https://doi.org/10.3390/biomedicines13102410

Chicago/Turabian Style

Yusa, Kazuyuki, Yuji Takeda, Nobuyuki Sasahara, Tomoharu Hemmi, Shigeo Ishikawa, and Tsuneo Konta. 2025. "Imbalance of Serum Bone-Metabolism-Related Factors Associated with Osteonecrosis of the Jaw" Biomedicines 13, no. 10: 2410. https://doi.org/10.3390/biomedicines13102410

APA Style

Yusa, K., Takeda, Y., Sasahara, N., Hemmi, T., Ishikawa, S., & Konta, T. (2025). Imbalance of Serum Bone-Metabolism-Related Factors Associated with Osteonecrosis of the Jaw. Biomedicines, 13(10), 2410. https://doi.org/10.3390/biomedicines13102410

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