Low-dose Risedronate Sodium Protects Bone Cells after Abrupt Oestrogen Withdrawal

Abstract

To investigate the effects of low-dose risedronate sodium on the in vitro cellular profile of osteoblasts, adipocytes, osteocytes and osteoclasts in a rat model of abrupt oestrogen deficiency. Oestrogen deficiency was induced by ovariectomy in 24 female rats. The rats were treated with low-dose (0.24 μg/kg) or high-dose (2.4 μg/kg) risedronate sodium for 4 days presurgery, continuing every 3 days until 15 days postsurgery. Osteogenic and adipogenic differentiation were determined in cultured bone marrow cells by alkaline phosphatase and Oil Red O staining, respectively, and by osteogenic and adipogenic gene expression. Osteoclast formation was measured in bone marrow cells stimulated with macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand, and stained with tartrate-resistant acid phosphatase. Osteocyte apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assay and B-cell lymphoma-2 (Bcl-2) immunohistochemistry. Low-dose risedronate sodium enhanced osteoblast differentiation, suppressed adipocyte differentiation and osteoclast formation, and reduced osteocyte apoptosis through regulation of Bcl-2 and Bcl-2-associated X protein. Low-dose risedronate sodium may have clinical benefit in protecting against bone loss after abrupt oestrogen deficiency.