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Predictive biomarkers of ossification progression and bone metabolism dynamics in patients with cervical ossification of the posterior longitudinal ligament

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Abstract

Purpose

This study aimed to establish biomarkers to predict the progression of ossification by examining ossification volume and bone metabolism dynamics in patients with ossification of the posterior longitudinal ligament (OPLL).

Methods

We assessed OPLL progression using computed tomography-based three-dimensional (3D) image analysis and examined bone metabolism dynamics in 107 patients with OPLL (men, 72; women, 35; mean age, 63.6 years). The volume of OPLL was calculated twice during the follow-up period, and OPLL progression was evaluated by the annual rate of ossification increase. Bone metabolism dynamics were assessed by routine blood tests and analysis of various serum biomarkers (including 25-hydroxyvitamin D, intact parathyroid hormone, fibroblast growth factor 23, intact N-terminal propeptide of type 1, tartrate-resistant acid phosphatase isoform 5b, sclerostin, and Dickkopf-1) and bone mineral density (BMD). Patients were classified into the progression (P) or non-progression (NP) group according to the annual rate of increase in previous 3D image analyses, and associated factors between these groups were compared.

Results

The P and NP groups consisted of 29 patients (23 men and 6 women) and 78 patients (49 men and 29 women), respectively. Univariate analysis revealed significant differences in terms of age, body mass index, serum phosphorus, serum sclerostin, and BMD. In multivariate analysis, age, serum phosphorus, and serum sclerostin were identified as independent factors associated with OPLL progression.

Conclusion

Younger age, hypophosphatemia, and high serum sclerostin are risk factors for OPLL progression. Serum phosphorus and sclerostin could serve as important biomarkers for predicting ossification progression.

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Data availability

The study data and details of materials used may be made available upon reasonable request by sending an e-mail to the first author.

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Acknowledgements

We greatly thank Nami Kira and Masanori Hirayama for their assistance in data collection.

Funding

This work was supported by JSPS KAKENHI Grant Number (JP18K16612) and by Health and Labor Science Research grants (201610008B).

Author information

Authors and Affiliations

  1. Spine Center, Department of Orthopedic Surgery, Niigata Central Hospital, 1-18 Shinkocho, Chuo-Ku, Niigata, 950-8556, Japan

    Keiichi Katsumi, Akiyoshi Yamazaki, Tatsuki Mizouchi, Masayuki Sato & Hiroyuki Sekimoto

  2. Department of Orthopedic Surgery, Niigata University Medical and Dental General Hospital, 1-757 Asahimachidori, Chuo-Ku, Niigata, 951-8510, Japan

    Keiichi Katsumi, Kei Watanabe, Masayuki Ohashi & Hiroyuki Kawashima

  3. Department of Orthopedic Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma City, Niigata, 949-7302, Japan

    Toru Hirano

  4. Department of Orthopedic Surgery, Niigata Minami Hospital, 2007-6, Toyano, Chuo-Ku, Niigata, 950-8601, Japan

    Tomohiro Izumi

  5. Department of Orthopedic Surgery, Niigata Prefectural Shibata Hospital, 1-2-8, Honcho, Shibata, Niigata, 957-8588, Japan

    Yohei Shibuya

Authors
  1. Keiichi Katsumi
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  2. Kei Watanabe
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  3. Akiyoshi Yamazaki
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  11. Hiroyuki Kawashima
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Contributions

KK, WK, TH, and TI designed the study; KK, KW, TH, MO, TM, MS, HS, and YS collected the data; KK, KW, AY, TH, and MO analyzed and interpreted the data; KK, KW, AY, and TH wrote the initial draft of the manuscript; KK, and MT performed the statistical analyses. KK, KW, AY, TH, MO, TM, MS, HS, TI, YS, and HK participated in revising the manuscript. KW, AY, TH, and HK supervised the study. KK, KW, and HK acquired the funding. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Keiichi Katsumi.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

Written informed consent was obtained from each study participant before enrollment at each institution. The study protocol was approved by the ethics committee at each participating institution, i.e., Niigata Central Hospital: et2020-03, Niigata University Medical and Dental General Hospital: 2015–2525, and Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital: 30–010.

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Katsumi, K., Watanabe, K., Yamazaki, A. et al. Predictive biomarkers of ossification progression and bone metabolism dynamics in patients with cervical ossification of the posterior longitudinal ligament. Eur Spine J 32, 1282–1290 (2023). https://doi.org/10.1007/s00586-023-07565-z

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  • DOI: https://doi.org/10.1007/s00586-023-07565-z

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