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

## TL;DR

This study shows that high doses of simvastatin, alone or with alendronate, may impair wound healing by reducing cell migration and key angiogenesis markers.

## Contribution

The study reveals new insights into how co-medication with bisphosphonates and statins affects wound healing in oral tissues.

## Key findings

- High simvastatin concentrations reduced cell migration and proliferation in osteoblasts and fibroblasts.
- Simvastatin and alendronate together decreased secreted levels of angiogenesis-related cytokines like VEGF and IL-8.
- Cell viability was largely unaffected despite impaired migration and cytokine secretion.

## Abstract

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.

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.

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.

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.