Montazerolghaem M, Rasmusson A, Melhus H, Engqvist H, Karlsson Ott M
Department of Engineering Sciences, Division of Applied Materials Science, Uppsala University, 751 21, Uppsala, Sweden.
Department of Medical Sciences, Section of Clinical Pharmacology, Uppsala University, 751 85, Uppsala, Sweden.
J Mater Sci Mater Med. 2016 May;27(5):83. doi: 10.1007/s10856-016-5692-7. Epub 2016 Mar 11.
Simvastatin, a cholesterol lowering drug, has been shown to have positive effects on fracture healing and bone regeneration based on its dual effect; bone anabolic and anti-resorptive. In this study the focus has been on the anti-resorptive effect of the drug and its impact on the degradation of acidic calcium phosphate cement. The drug was added to the pre-mixed acidic cement in three different doses (0.1, 0.25 and 0.5 mg/g cement) and the release was measured. Furthermore the effect of the loaded cements on osteoclast differentiation and resorption was evaluated by TRAP activity, number of multinucleated cells, gene expression and calcium ion concentration in vitro using murine bone marrow macrophages. The simvastatin did not affect the cell proliferation while it clearly inhibited osteoclastic differentiation at all three doses as shown by TRAP staining, TRAP activity and gene expression. Consistent with these results, simvastatin also impaired resorption of cements by osteoclasts as indicated by reduced calcium ion concentrations. In conclusion, our findings suggest that simvastatin-doped pre-mixed acidic calcium phosphate cement inhibits the osteoclastic mediated resorption of the cement thus slowing down the degradation rate. In addition with simvastatin's bone anabolic effect it makes the cement-drug combination a promising bone graft material, especially useful for sites with compromised bone formation.
辛伐他汀是一种降胆固醇药物，基于其骨合成代谢和抗吸收的双重作用，已被证明对骨折愈合和骨再生具有积极影响。在本研究中，重点是该药物的抗吸收作用及其对酸性磷酸钙骨水泥降解的影响。将该药物以三种不同剂量（0.1、0.25和0.5毫克/克骨水泥）添加到预混合的酸性骨水泥中，并测量其释放情况。此外，使用小鼠骨髓巨噬细胞，通过抗酒石酸酸性磷酸酶（TRAP）活性、多核细胞数量、基因表达和钙离子浓度，在体外评估负载骨水泥对破骨细胞分化和吸收的影响。辛伐他汀不影响细胞增殖，但如TRAP染色、TRAP活性和基因表达所示，在所有三种剂量下均明显抑制破骨细胞分化。与这些结果一致，辛伐他汀还通过降低钙离子浓度表明，损害破骨细胞对骨水泥的吸收。总之，我们的研究结果表明，掺杂辛伐他汀的预混合酸性磷酸钙骨水泥可抑制破骨细胞介导的骨水泥吸收，从而减缓降解速度。此外，由于辛伐他汀的骨合成代谢作用，使骨水泥-药物组合成为一种有前景的骨移植材料，尤其适用于骨形成受损的部位。
