Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells

Area of Science:

• Biomedical Science
• Cell Biology
• Pharmacology

Background:

• Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is a serious side effect linked to bisphosphonate therapy.
• The precise mechanisms underlying BP-ONJ pathogenesis remain unclear, with potential roles for both bone and soft tissue impairment.

Purpose of the Study:

• To investigate the in vitro effects of nitrogen-containing and non-nitrogen-containing bisphosphonates on human endothelial cells, fibroblasts, and osteogenic cells.
• To explore the potential correlation between bisphosphonate cellular impact and the incidence of BP-ONJ.

Main Methods:

• Utilized cell viability assays and scratch wound assays to assess the impact of bisphosphonates on human umbilical cord vein endothelial cells (HUVEC), fibroblasts, and osteogenic cells.
• Employed confocal laser scanning microscopy to visualize the morphological changes in vital-stained osteogenic cells.

Main Results:

• Pamidronate and zoledronate exhibited the most significant negative effects across all tested cell lines.
• Ibandronate and clodronate demonstrated less pronounced impacts, with clodronate showing minimal effects on HUVEC and fibroblasts.
• Morphological alterations were observed in osteogenic cells, particularly with potent bisphosphonates.

Conclusions:

• BP-ONJ may arise from multifactorial events involving impairments in multiple cell types.
• The differential impact of bisphosphonates on non-bone cells, especially potent ones, could contribute to the higher prevalence of BP-ONJ.
• Altered cellular responses may lead to compromised wound healing in BP-ONJ development.