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Targeting a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts
Tormod B Krüger1, Unni Syversen2,3,4, Bente B Herlofson1
1Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Objective:
Bisphosphonates like alendronate mainly exert their effects on osteoclasts. However, osteoblasts are also affected, but exposed to a much lower concentration in vivo than the osteoclasts. Given that the effects are dose-dependent, the intention of the study was to identify a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts.
Materials And Methods:
Primary human osteoblasts were incubated with alendronate (5, 20 and 100 µM) for 1, 3, 7 and 14 days. Proliferation and viability were assessed, and the effects on cellular growth and function were evaluated by multianalyte profiling of selected proteins in cell culture media using the Luminex 200TM.
Results:
The viability was not affected by any of the dosages. Exposure to 5 µM alendronate had a neutral effect on osteoblast proliferation, and on secretion of osteogenic and inflammatory markers, while enhancing synthesis of a marker of angiogenesis. 20 µM alendronate induced a decline in proliferation and affected angiogenic and osteogenic biomarkers adversely. 100 µM alendronate reduced proliferation dramatically, and this dosage was excluded from further experiments.
Conclusion:
A concentration of 5 µM alendronate exerted effects on human osteoblasts that may translate to those observed in vivo and could therefore be relevant for in vitro studies.
