Decreased circulating dopamine β-hydroxylase is associated with medication-related osteonecrosis of the jaw and implicates sympathetic dysregulation
10 affiliations
- 1Department of Oral Histology and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 03080 Republic of Korea
- 2Department of Dental Sciences, School of Dentistry, Seoul National University, Seoul, 08826 Republic of Korea
- 3Institute for Data Innovation in Science, Seoul National University, Seoul, 08826 Republic of Korea
- 4Graduate School of Medical Sciences, Ewha Womans University, Seoul, 03760 Republic of Korea
- 5Department of Dentistry, Institute of Medical Science, Gyeongsang National University School of Medicine, Jinju, 52727 Republic of Korea
- 6Department of Anatomy, School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea
- 7Department of Oral and Maxillofacial Surgery, Yonsei University College of Dentistry, Seoul, 03722 Republic of Korea
- 8Dental Multiomics Center, Dental Research Institute, Seoul National University, Seoul, 08826 Republic of Korea
- 9Department of Oral and Maxillofacial Surgery, College of Medicine, Ewha Womans University, Seoul, 03760 Republic of Korea
- 10Ewha Dental AI & Bio Innovation Global Research Institute, Ewha Womans University, Seoul, Korea
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive therapy, yet no reliable circulating biomarker exists for risk stratification. Using an unbiased serum proteomics approach in a multicentre framework, we identified dopamine β-hydroxylase (DBH) as a differentially expressed protein with significantly lower levels in patients with MRONJ. This finding was validated in an independent clinical cohort and further supported in the UK Biobank population. Circulating DBH levels were positively associated with blood-pressure traits, consistent with its role as a surrogate marker of sympathetic nervous system activity, and suggesting that reduced DBH levels in MRONJ may reflect altered sympathetic regulation. In a mouse model, pharmacological sympathetic inhibition with propranolol exacerbated jaw osteonecrosis and further suppressed osteoclast activity in the presence of zoledronic acid. Osteoblast–osteoclast co-culture experiments demonstrated additive inhibitory effects on osteoclast differentiation under β-adrenergic blockade. Together, these findings support an association between reduced circulating DBH levels and MRONJ and suggest that sympathetic dysregulation may contribute to disease pathogenesis. Circulating DBH may serve as a candidate biomarker for risk assessment and disease monitoring in patients receiving antiresorptive therapy.
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BibTeX
@article{lee2026decreased,
title = {{Decreased circulating dopamine β-hydroxylase is associated with medication-related osteonecrosis of the jaw and implicates sympathetic dysregulation}},
author = {Kyeongho Lee and Hana Cho and June Yeon Kim and Hyun Hwang and Ji-Soo Song and Soyoung Yoon and Sunbin Jung and Young-Hoon Kang and Yun Hak Kim and Jun-Young Kim and Sung-Jin Kim and Hankum Park and Jin-Woo Kim},
journal = {Experimental \& Molecular Medicine},
year = {2026},
month = oct,
doi = {10.1038/s12276-026-01868-z},
url = {https://doi.org/10.1038/s12276-026-01868-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Decreased circulating dopamine β-hydroxylase is associated with medication-related osteonecrosis of the jaw and implicates sympathetic dysregulation
AU - Kyeongho Lee
AU - Hana Cho
AU - June Yeon Kim
AU - Hyun Hwang
AU - Ji-Soo Song
AU - Soyoung Yoon
AU - Sunbin Jung
AU - Young-Hoon Kang
AU - Yun Hak Kim
AU - Jun-Young Kim
AU - Sung-Jin Kim
AU - Hankum Park
AU - Jin-Woo Kim
PY - 2026
DA - 2026/10/14
JO - Experimental & Molecular Medicine
DO - 10.1038/s12276-026-01868-z
UR - https://doi.org/10.1038/s12276-026-01868-z
AB - Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive therapy, yet no reliable circulating biomarker exists for risk stratification. Using an unbiased serum proteomics approach in a multicentre framework, we identified dopamine β-hydroxylase (DBH) as a differentially expressed protein with significantly lower levels in patients with MRONJ. This finding was validated in an independent clinical cohort and further supported in the UK Biobank population. Circulating DBH levels were positively associated with blood-pressure traits, consistent with its role as a surrogate marker of sympathetic nervous system activity, and suggesting that reduced DBH levels in MRONJ may reflect altered sympathetic regulation. In a mouse model, pharmacological sympathetic inhibition with propranolol exacerbated jaw osteonecrosis and further suppressed osteoclast activity in the presence of zoledronic acid. Osteoblast–osteoclast co-culture experiments demonstrated additive inhibitory effects on osteoclast differentiation under β-adrenergic blockade. Together, these findings support an association between reduced circulating DBH levels and MRONJ and suggest that sympathetic dysregulation may contribute to disease pathogenesis. Circulating DBH may serve as a candidate biomarker for risk assessment and disease monitoring in patients receiving antiresorptive therapy.
SN - 1226-3613
SN - 2092-6413
ER -