Bisphosphonate and statin: adverse effects of co-medication on wound healing in in vitro models of periodontal tissues

Authors

  • Agnes Småland-Reksten Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway
  • Anne E. Agger Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway
  • Aina M. Lian Oral Research Laboratory, Faculty of Dentistry, University of Oslo, Oslo, Norway
  • Janne E. Reseland Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway
  • Tormod B. Krüger Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway

DOI:

https://doi.org/10.2340/aos.v85.45585

Keywords:

Bisphosphonate, alendronate, statin, simvastatin, osteonecrosis

Abstract

Objective: Bisphosphonates and statins may influence wound healing and are frequently prescribed to the same patient group. Bisphosphonates may induce osteonecrosis of the jaw; however, little information is available on the cellular mechanisms and biological effects of co-medication in oral tissues. The aim was to assess the effects of alendronate and simvastatin, both alone and combined, on osteoblasts and gingival fibroblasts in vitro.

Study design: Primary human gingival fibroblasts and primary human osteoblasts were incubated with alendronate (5 µM) and simvastatin (1, 5 or 10 µM), alone or combined, for up to 14 days. Cells were assessed for viability by measuring lactate dehydrogenase activity and caspase-3 concentration in the cell culture media. Migration and proliferation potential was assessed by scratch-wound assay. Secreted levels of cytokines/chemokines were measured using Luminex 200 multianalytic profiling.

Results: High concentrations of simvastatin, both alone and combined with alendronate, affected the proliferation/migration potential and reduced scratch closure. The same exposure induced near abolishment of secreted levels of cytokines affecting angiogenesis, such as VEGF, IL-6, IL-8, and MCP-1, however little effect was found on cell viability.

Conclusion: High concentrations of simvastatin, alone or combined with alendronate, may have a negative impact on angiogenetic markers and cell migration/proliferation, affecting wound healing and growth.

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Published

2026-03-18