Calcified Tissue International

, Volume 101, Issue 6, pp 553–563 | Cite as

Does Oxidative Stress Play a Role in Altered Characteristics of Diabetic Bone? A Systematic Review

  • Miljana Bacevic
  • Bozidar Brkovic
  • Adelin Albert
  • Eric Rompen
  • Regis P. Radermecker
  • France LambertEmail author


Diabetes mellitus (DM) has been associated with increased bone fracture rates, impaired bone regeneration, delayed bone healing, and depressed osteogenesis. However, the plausible pathogenic mechanisms remain incompletely understood. The aim of the present systematic review was to investigate whether oxidative stress (OS) plays a role in altered characteristics of diabetic bone under in vivo conditions. An electronic search of the MEDLINE (via PubMed) and Embase databases was performed. In vivo animal studies involving DM and providing information regarding assessment of OS markers combined with analyses of bone histology/histomorphometry parameters were selected. A descriptive analysis of selected articles was performed. Ten studies were included in the present review. Both bone formation and bone resorption parameters were significantly decreased in the diabetic groups of animals compared to the healthy groups. This finding was consistent regardless of different animal/bone models employed or different evaluation periods. A statistically significant increase in systemic and/or local OS status was also emphasised in the diabetic groups in comparison to the healthy ones. Markers of OS were associated with histological and/or histomorphometric parameters, including decreased trabecular bone and osteoid volumes, suppressed bone formation, defective bone mineralisation, and reduced osteoclastic activity, in diabetic animals. Additionally, insulin and antioxidative treatment proved to be efficient in reversing the deleterious effects of high glucose and associated OS. The present findings support the hypotheses that OS in the diabetic condition contributes at least partially to defective bone features, and that antioxidative supplementation can be a valuable adjunctive strategy in treating diabetic bone disease, accelerating bone healing, and improving osteointegration.


Oxidative stress Diabetes mellitus Bone features Antioxidants Review 



The authors are grateful to Prof. Réne Rizzoli, Prof. Olivier Bruyère, and Dr. Véronique Rabenda for their insightful comments and helpful suggestions for improvement of the manuscript.

Author Contributions

MB, BB, and FL designed the study. FL is the guarantor. MB, BB, and FL performed the literature search and collected the data. MB, BB, AA, ER, RR, and FL analysed and interpreted the data. AA is responsible for statistical analysis of the data. MB and FL drafted this manuscript. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and ensure that any questions relating to the accuracy and integrity of the study are investigated and properly resolved.

Compliance with Ethical Standards

Conflicts of interest

Miljana Bacevic, Bozidar Brkovic, Adelin Albert, Eric Rompen, Regis P. Radermecker, and France Lambert declare that they have no conflicts of interest. No external funding was available for this study, except for the internal support of the authors’ institution.

Supplementary material

223_2017_327_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb) Appendix I Reason(s) for exclusion
223_2017_327_MOESM2_ESM.docx (19 kb)
Supplementary material 2 (DOCX 19 kb) Appendix II The selected studies
223_2017_327_MOESM3_ESM.docx (19 kb)
Supplementary material 3 (DOCX 19 kb) Appendix III The algorithm used for electronic search in PubMed


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Miljana Bacevic
    • 1
    • 2
  • Bozidar Brkovic
    • 2
  • Adelin Albert
    • 3
  • Eric Rompen
    • 4
  • Regis P. Radermecker
    • 5
  • France Lambert
    • 4
    • 1
    • 6
    Email author
  1. 1.Dental Biomaterials Research Unit (d-BRU), Faculty of MedicineUniversity of LiegeLiègeBelgium
  2. 2.Clinic of Oral Surgery, School of Dental MedicineUniversity of BelgradeBelgradeSerbia
  3. 3.Department of BiostatisticsUniversity Hospital of LiegeLiègeBelgium
  4. 4.Department of Periodontology and Oral Surgery, Faculty of MedicineUniversity of LiegeLiègeBelgium
  5. 5.Department of Diabetes, Nutrition and Metabolic DisordersUniversity Hospital of LiegeLiègeBelgium
  6. 6.Service de Médecine DentaireLiègeBelgium

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