Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells

Introduction: Alendronate (ALN) prevents bone loss in postmenopausal patients through the regulation of osteoclastic activity. However, it has also proven to be effective in older adults where the pathophysiological mechanism is the predominance of adipogenesis over osteoblastogenesis. The aim of this study is to determine the in vitro effect of ALN on both osteoblastogenesis and adipogenesis. Materials and Methods: Human mesenchymal stem cells (MSCs) were plated at a density of 5 x 10(5) cells/well in 100-cm(2) dishes containing MSC growth media. After confluence, cells were committed to differentiate adding either adipogenic or osteogenic media with and without 1,25(OH)(2)D-3 (10(-8) M) and supplemented with ALN at increasing concentrations (10(-9) to 10(-7) M). Untreated differentiating MSCs were used as control. Alkaline phosphatase (ALP), oil red 0, and Alizarin red staining were performed at timed intervals (weeks I and 2). Additionally, levels of expression of both osteogenesis and adipogenesis transcription factors were measured in protein extracts. Finally, the effect of ALN on PPAR gamma 2 nuclear activation complex was assessed. Results: We found that ALN has a significant and dose-dependent effect on osteoblastogenesis. This effect was not modified by the presence of 1,25(OH)(2)D-3 in the medium. Furthermore, adipogenic differentiation of MSCs was affected by addition of both ALN and 1,25(OH)(2)D-3 to the media as confirmed by phenotype changes and lower number of lipid droplets. Finally, expression of adipogenic transcription factors and PPAR gamma 2 activation were reduced in adipose differentiating MSCs treated with either ALN or ALN + 1125(OH)(2)D-3. Conclusions: This study shows a potential anabolic effect of ALN in vitro through the stimulation of osteogenic differentiation of MSCs. Additionally, a previously unknown inhibitory effect of ALN on bone marrow adipogenesis was also found.