Previous studies of the direct actions of bisphosphonates on bone have mainly been limited to their effects on bone-resorbing osteoclasts and little is known about the direct effects of bisphosphonates on osteoblasts. Here we report the direct effects of alendronate on the proliferation and osteogenic differentiation of the MG-63 osteoblast-like cell line. Cell proliferation was determined with the MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay, osteogenic differentiation was evaluated with an alkaline phosphatase bioassay and by analysis of gene expression by reverse transcription-polymerase chain reaction, and the extent of calcium deposition was measured using Alizarin Red S staining. Alendronate significantly increased cell numbers over control values, with the greatest effect at 10−8 M. Alkaline phosphatase activity and gene expression of bone morphogenetic protein 2, type I collagen and osteocalcin were increased after alendronate treatment. Alendronate also stimulated calcium deposition. We conclude that alendronate, apart from inhibiting osteoclastic bone resorption, is also a promoter of osteoblast proliferation and maturation.
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