Relationship between rheumatoid arthritis and osteoporosis.

类风湿性关节炎患者有广泛性骨质疏松症的报道。然而，尚不确定这是由于疾病本身还是由于类固醇治疗或缺乏运动等相关因素。我们分析糖皮质激素对8周龄大鼠胫骨骨髓消融后骨再生的影响。甲泼尼龙琥珀酸钠（MPSS）以100mg /kg/天的剂量肌肉注射，连续3天。消融后第1、3、5、7、10、12、14天胫骨行抗酒石酸酸性磷酸酶（TRAP）染色、免疫组化、原位杂交、透射电镜（TEM），测定新生骨体积和破骨细胞数量。MPSS处理组第7天新生骨体积明显减少，第10天仍有未成熟骨存在。该骨的体积明显高于对照组。但各组间破骨细胞数量、成骨细胞分化标志物mrna表达、碱性磷酸酶和组织蛋白酶K免疫组化检测均无差异。TEM结果显示，成骨细胞的形态没有差异，而与对照组相比，mpss治疗组的破骨细胞有较少的褶皱边界。这些结果表明，MPSS治疗既不影响成骨细胞的分化，也不影响成骨细胞的形态，也不改变破骨细胞的数量和组织蛋白酶K水平。然而，大剂量MPSS抑制大鼠胫骨骨髓消融后骨再生过程中的骨形成和骨吸收，抑制破骨细胞皱边形成。这些数据将有助于开发骨再生疗法的骨疾病，由于高剂量类固醇给药。

Generalized osteoporosis has been reported in patients with rheumatoid arthritis. However, it is uncertain whether this is due to the disease itself or to related factors such as steroid treatment or inactivity. We analyzed the effect of glucocorticoid on bone regeneration after bone marrow ablation in tibiae of eight-week-old rats. Methylprednisolone sodium succinate (MPSS) was injected intramuscularly at a dose of 100 mg/kg/day for 3 days. Tibiae on days 1, 3, 5, 7, 10, 12 and 14 after ablation were subjected to tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry, in situ hybridization, and transmission electron microscopy (TEM), and measurement of the volume of newly-formed bone and the osteoclast number. MPSS significantly decreased the newly-formed bone volume on day 7, and immature bone still remained on day 10 in the MPSS-treated group. The volume of this bone was significantly higher than that in the control group. However, there were no differences between the groups in the osteoclast number, the expression of mRNAs for osteoblast differentiation markers, and alkaline phosphatase and cathepsin K judged by immunohistochemistry. TEM findings showed no difference in the form of osteoblasts, whereas osteoclasts in the MPSS-treated group had less developed ruffled borders, compared to those in the control group. These results suggest that MPSS treatment affects neither the differentiation nor the shape of osteoblasts, and does not change the osteoclast number or the cathepsin K level. However, high dose MPSS inhibits both bone formation and resorption during bone regeneration after rat tibial bone marrow ablation, and inhibits ruffled border formation in osteoclasts. These data will be useful to develop bone regenerative therapies for bone diseases due to high dose steroid administration.