Serum biomarkers for bisphosphonate-related osteonecrosis of the jaw: a prospective clinical study

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Summary: In this prospective study, serum levels of 12 possible biomarkers were compared between osteonecrosis of the jaw (ONJ) and control groups, before and after dentoalveolar surgery. The results suggest that patients with abnormal serum levels of specific biomarkers should be monitored closely for the prevention and early diagnosis of ONJ. Introduction: Bisphosphonate-related osteonecrosis of the jaw (ONJ) is an adverse effect of long-term bisphosphonate therapy. This study aimed to identify bone biomarkers for ONJ risk assessment and diagnosis. Methods: This prospective study included patients with histories of bisphosphonate therapy without current ONJ who were in need of dentoalveolar surgery of the jaw area. Serum levels of 12 possible bone markers, selected based on their involvement in ONJ pathogenesis, were compared between ONJ and control groups before dentoalveolar surgery (T0), at 8 postoperative weeks (T1), and at 4 months after diagnosis(T2). Results: Seventy-six patients who met the inclusion criteria were included in the study; 33 were assigned to the ONJ group, and 43 patients without ONJ signs or symptoms after dentoalveolar surgery were assigned to the control group. In the ONJ group, at both T0 and T1, the mean tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) levels were significantly lower and the mean Dickkopf-related protein 1 (DKK1) levels were significantly higher than the corresponding values for the control group. Linear mixed model analysis revealed significant group effects over time for serum TRACP 5b and DKK1 after adjusting for demographic, pharmacological, and diagnostic variables. Lower serum levels of TRACP 5b under a specified cut-off value (≤ 2.899 U/L) at T0 indicated a 20.40-fold increased risk of ONJ development. Conclusion: Patients with abnormally low serum levels of TRACP 5b and high serum levels of DKK1 should be monitored closely before and after dentoalveolar surgery for the prevention and early diagnosis of ONJ.

Original languageEnglish
Pages (from-to)367-377
Number of pages11
JournalOsteoporosis International
Issue number2
StatePublished - Feb 2022

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1A2C4001842).

Publisher Copyright:
© 2021, International Osteoporosis Foundation and National Osteoporosis Foundation.


  • Biomarker
  • Bisphosphonate
  • Dickkopf-related protein 1
  • Osteonecrosis of the jaw
  • Tartrate-resistant acid phosphatase isoform 5b


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