Division of Orthopaedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Bone Miner Metab. 2012 Nov;30(6):609-18. doi: 10.1007/s00774-012-0369-x. Epub 2012 Jul 18.
The aim of the study was to determine the effect of alendronate on resorption of β-tricalcium phosphate (β-TCP) and bone formation in rats with adjuvant-induced arthritis (AIA). After preparation of a model of AIA in rats (day 0), alendronate or vehicle was injected intraperitoneally once daily five times in a week. Cylindrical β-TCP was implanted into the rat femoral condyle on day 7. Rats were killed on days 12, 15, and 21, and specimens and serum samples were collected. Specimens were analyzed by tartrate-resistant acid phosphate (TRAP) staining, immunohistochemistry of the ED1 protein, and in situ hybridization with digoxigenin-labeled α1 chain of type I procollagen (COL1A1). Mineralized bone sections were analyzed by Villanueva bone stain. The serum osteocalcin level was measured using an enzyme-linked immunosorbent assay kit. Alendronate decreased the number of TRAP-positive cells attached to β-TCP, the numbers of ED1-positive multinucleated giant cells, and resorption of β-TCP. In AIA rats treated with alendronate, COL1A1 mRNA-positive cells adhered to β-TCP were round or cuboid whereas the cells in untreated AIA rats were fibroblast-like cells. Alendronate increased calcification of newly formed bone whereas it did not restore the bone formation suppressed with inflammation. These results suggest that alendronate has the potential to conduct mature bone after implantation of β-TCP in AIA. Alendronate may help to reduce insufficiency of newly formed bone after implantation of β-TCP in diseases characterized by increased bone resorption such as rheumatoid arthritis.
本研究旨在探讨阿仑膦酸钠对佐剂性关节炎（AIA）大鼠β-磷酸三钙（β-TCP）吸收和骨形成的影响。在成功制备 AIA 大鼠模型（第 0 天）后，阿仑膦酸钠或载体通过腹腔注射的方式每周给药 5 次，每天 1 次。第 7 天，将圆柱形 β-TCP 植入大鼠股骨髁。第 12、15 和 21 天处死大鼠，收集标本和血清样本。通过抗酒石酸酸性磷酸酶（TRAP）染色、ED1 蛋白免疫组化和 DIG 标记的Ⅰ型前胶原α1 链（COL1A1）原位杂交分析标本。通过 Villanueva 骨染色分析矿化骨切片。采用酶联免疫吸附试验试剂盒测定血清骨钙素水平。阿仑膦酸钠减少了附着于 β-TCP 的 TRAP 阳性细胞、ED1 阳性多核巨细胞的数量和 β-TCP 的吸收。在用阿仑膦酸钠治疗的 AIA 大鼠中，附着于 β-TCP 的 COL1A1 mRNA 阳性细胞呈圆形或方形，而未用阿仑膦酸钠治疗的 AIA 大鼠中的细胞呈成纤维细胞样。阿仑膦酸钠增加了新形成骨的钙化，但未恢复炎症抑制的骨形成。这些结果表明，阿仑膦酸钠在 AIA 大鼠中植入β-TCP 后具有促进成熟骨形成的潜力。阿仑膦酸钠可能有助于减少类风湿关节炎等骨吸收增加疾病中β-TCP 植入后新形成骨的不足。
