Relationship between rheumatoid arthritis and osteoporosis.

类风湿性关节炎患者中已有泛发性骨质疏松的报道。然而，目前还不确定这是由于疾病本身还是相关因素，如类固醇治疗或缺乏活动。我们分析了糖皮质激素对8周龄大鼠胫骨骨髓消融后骨再生的影响。甲基强的松龙琥珀酸钠(MPSS)100 mg/(kg·d)肌肉注射，连续3d。分别于术后第1、3、5、7、10、12、14天取胫骨进行抗酒石酸酸性磷酸酶(TRAP)染色、免疫组织化学、原位杂交和透射电子显微镜观察，并测量新生骨体积和破骨细胞数。MPSS组第7天新生骨体积明显减少，第10天仍有未成熟骨存在。骨体积明显大于对照组。但在破骨细胞数量、成骨细胞分化标志物的mRNAs表达、免疫组织化学判断碱性磷酸酶和组织蛋白酶K方面，两组间差异无统计学意义。透射电子显微镜观察结果显示，成骨细胞的形态没有差异，而MPSS处理组的破骨细胞与对照组相比，有较少的皱纹。这些结果表明，MPSS处理不影响成骨细胞的分化和形态，也不改变破骨细胞的数量和组织蛋白酶K的水平。然而，高剂量的MPSS抑制了大鼠胫骨骨髓切除后骨再生过程中的骨形成和骨吸收，并抑制了破骨细胞褶皱边缘的形成。这些数据将有助于开发骨再生疗法，以治疗因大剂量使用类固醇而引起的骨病。

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.