Is TIMP-1 a biomarker for periodontal disease? A systematic review and meta-analysis

Puk de Brouwer, Floris J. Bikker, Henk S. Brand, Wendy E. Kaman*

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


Objective: One of the most important families of proteases associated with periodontal disease is the family of the matrix metalloproteinases (MMPs). Their activity is regulated by tissue inhibitors of metalloproteinases (TIMPs), and an imbalance between MMP activity and regulation by TIMPs has been associated with the progression of periodontal disease. This strong interaction between TIMPs and MMPs might be an indication that TIMPs can be used as a biomarker to monitor periodontal disease progression in oral fluids. In particular, TIMP-1 is a frequently studied biomarker for periodontal diseases. Therefore, the aim of this systematic review was to evaluate the scientific literature regarding TIMP-1 concentrations in oral fluids of patients suffering from periodontitis or gingivitis in comparison to healthy individuals. Material and Methods: PubMed/ MedLine and Web of Science databases were searched electronically. Studies that met the inclusion criteria were systematically evaluated and assessed for eligibility and risk of bias. Meta-analysis was performed through the random effects model to assess the association between periodontitis/gingivitis and TIMP-1 concentration in stimulated saliva, unstimulated saliva, and gingival crevicular fluid (GCF). Results: The search strategy provided a total of 322 studies of which 10 studies met all inclusion criteria. Two studies investigated TIMP-1 concentrations in GCF, three studies in unstimulated saliva, and five studies investigated TIMP-1 concentrations in stimulated saliva. Three studies revealed that TIMP-1 levels in oral fluids were significantly decreased in periodontal disease. Meta-analysis revealed that there is no statistically significant difference between TIMP-1 concentration in oral fluids of periodontitis/gingivitis patients in comparison to healthy individuals. Conclusions: This systematic review with meta-analysis shows that periodontal diseases are not associated with a statistically significant change in TIMP-1 concentration in oral fluids.

Original languageEnglish
Pages (from-to)235-245
Number of pages11
JournalJournal of Periodontal Research
Issue number2
Early online date1 Dec 2021
Publication statusPublished - Apr 2022

Bibliographical note

Funding Information:
No external funding, apart from the support of the authors’ institution, was available for this study.

Publisher Copyright:
© 2021 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.


  • biomarker
  • gingivitis
  • periodontitis
  • TIMP-1
  • tissue inhibitor of metalloproteases


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