Li Mei, Jiao Jie, Meng Xu-wu, Xing Xiao-ping, Xia Wei-bo, Zhou Xue-ying, Liu Huai-cheng, Jiang Yan, Wang Ou, Hu Ying-ying, Zhan Zhi-Wei
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2005 Feb 2;85(5):335-8.
OBJECTIVE: To investigate the effects of teriparatide (hPTH1-34, PTH) and alendronate (Alen) on bone turnover rate and bone mineral density (BMD) of ovariectomized (OVX) osteoporotic rats. METHODS: 70 female 6-month-old Wistar rats were randomly divided into 7 groups: (1) baseline group: killed immediately as baseline controls; (2) sham operation group: injected subcutaneously with normal saline (NS) as normal controls; (3) OVXb group: underwent ovarietomy (OVX) and killed 6 weeks after OVX as pre-therapeutic controls; (4) OVXe group: injected with NS subcutaneously and then sacrificed 14 weeks after OVX as controls by the end of treatment; (5) PTH group: PTH 40 microg.kg(-1).d(-1) was administered; (6) Alen group: Alen 100 microg.kg(-1).d(-1) was administered; (7) A + P group: PTH 40 microg.kg(-1).d(-1) and Alen 100microg.kg(-1).d(-1) were administered. In groups 4 approximately 7, different medicines were injected subcutaneously QD 5 times per week from the 6th week to the 14th week after OVX and then the rats were killed and their right femurs, lumbar vertebrae, and samples of blood and urine were collected. Absorptometry was used to measure the BMD of the right femur and lumbar vertebrae. The serum calcium, phosphate, creatinine, alanine transaminase, and alkaline phosphatase (ALP) activity were measured by automatic biochemical analysis. The bone resorption marker urine deoxypyridinoline/creatinine (UDpd/Cr) level was measured by enzyme-linked immuosorbent assay. RESULTS: Six weeks after OVX the ALP and UDpd/Cr levels in the OVXb group were 101 U/L +/- 59 U/L and (118 +/- 32) x 10(-6) respectively, both significantly higher than those of the baseline group (58 U/L +/- 10 U/L and (48 +/- 34) x 10(-6) respectively, both P < 0.01) and the BMD results of the OVXb group were all significantly lower than those in the baseline group (all P < 0.01), which indicated that an OVX osteoporotic rat model was established successfully. The ALP and UDpd/Cr levels of the Alen group were 61 U/L +/- 28 U/L and (17 +/- 39) x 10(-6), significantly lower than those of the PTH group 120 U/L +/- 36 U/L and (111 +/- 26) x 10(-6) respectively, both P < 0.01) and the UDpd/Cr levels of the A + P group were between those of the Alen group and those of the PTH group. The BMD levels of the femur and lumbar vertebrae of the PTH, Alen, and A + P groups were all significantly higher than those of the control groups (all P < 0.01), and were similar to or higher than those of the sham operation group without significant differences between the PTH and Alen groups. The BMD level of the lumber vertebrae of the A + P group were significantly higher than those in the PTH group (all P < 0.05), and the femoral BMD results of the A + P group were significantly higher than those in the PTH and Alen groups (all P < 0.01). CONCLUSION: PTH and Alen are all effective on osteoporosis. In particular, the combination of PTH and Alen is more effective on increasing the BMD level.
目的：探讨特立帕肽（hPTH1-34，PTH）和阿仑膦酸盐（Alen）对去卵巢（OVX）骨质疏松大鼠骨转换率和骨密度（BMD）的影响。 方法：将70只6月龄雌性Wistar大鼠随机分为7组：（1）基线组：立即处死作为基线对照；（2）假手术组：皮下注射生理盐水（NS）作为正常对照；（3）OVXb组：行卵巢切除术（OVX），OVX后6周处死作为治疗前对照；（4）OVXe组：皮下注射NS，OVX后14周处死作为治疗结束时对照；（5）PTH组：给予PTH 40μg·kg⁻¹·d⁻¹；（6）Alen组：给予Alen 100μg·kg⁻¹·d⁻¹；（7）A + P组：给予PTH 40μg·kg⁻¹·d⁻¹和Alen 100μg·kg⁻¹·d⁻¹。在第4组至第7组中，从OVX后第6周开始至第14周，每周皮下注射不同药物5次，然后处死大鼠，收集其右股骨、腰椎以及血液和尿液样本。采用骨密度仪测量右股骨和腰椎的骨密度。通过自动生化分析仪检测血清钙、磷、肌酐、丙氨酸转氨酶和碱性磷酸酶（ALP）活性。采用酶联免疫吸附测定法测量骨吸收标志物尿脱氧吡啶啉/肌酐（UDpd/Cr）水平。 结果：OVX后6周，OVXb组的ALP和UDpd/Cr水平分别为101 U/L±59 U/L和（118±32）×10⁻⁶，均显著高于基线组（分别为58 U/L±10 U/L和（48±34）×10⁻⁶，均P<0.01），且OVXb组的骨密度结果均显著低于基线组（均P<0.01），这表明成功建立了OVX骨质疏松大鼠模型。Alen组的ALP和UDpd/Cr水平分别为61 U/L±28 U/L和（17±39）×10⁻⁶，显著低于PTH组（分别为120 U/L±36 U/L和（111±26）×10⁻⁶，均P<0.01），且A + P组的UDpd/Cr水平介于Alen组和PTH组之间。PTH组、Alen组和A + P组的股骨和腰椎骨密度水平均显著高于对照组（均P<0.01），且与假手术组相似或高于假手术组，PTH组和Alen组之间无显著差异。A + P组腰椎的骨密度水平显著高于PTH组（均P<0.05），A + P组股骨的骨密度结果显著高于PTH组和Alen组（均P<0.01）。 结论：PTH和Alen对骨质疏松均有效。特别是，PTH与Alen联合使用在提高骨密度水平方面更有效。
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