甲状旁腺素片段与阿仑膦酸钠对骨质疏松大鼠骨转换和骨密度的影响

目的　观察人甲状旁腺素氨基端 1- 34片段 (hPTH1 -34,简称PTH)与阿仑膦酸钠(Alen)对去卵巢骨质疏松大鼠骨转换和骨密度 (BMD)的影响。方法　70只 6月龄Wistar大鼠被随机分为 7组: (1)基线组;余 6组行去卵巢(OVX)或假手术(Sham); (2) (OVX6)周处死组; (3)假手术对照组; (4)OVX14周处死组; (5)PTH组:OVX后再给予 40μg·kg 1·d 1; (6)Alen组:OVX后再给予 100μg·kg 1·d 1; (7)A+P组:OVX后再给予Alen100μg·kg 1·d 1和PTH40μg·kg 1·d 1, (3)~(7)组均于OVX6周后开始皮下注射不同药物, 5d/周,疗程 8周。采用双能X线骨密度仪测量腰椎和股骨BMD,测量血碱性磷酸酶 (ALP)、钙、磷、肌酐水平,采用酶联免疫吸附法测量尿脱氧吡啶啉 /肌酐比值(UDpd/Cr)。结果　大鼠去卵巢后 6周组,ALP及UDpd/Cr明显高于基线组 (ALP: 101U/L±59U/L, 58U/L±10U/LP<0 01),腰椎BMD明显低于基线组 (P<0 01)。ALP及UDpd/Cr水平在Alen组明显降低(ALP: 61U/L±28U/L),PTH组显著升高(120U/L±36U/L),A+P组介于Alen和PTH组之间。PTH、Alen及A+P组腰椎和股骨BMD显著高于骨质疏松对照组 (分别P<0. 01或P<0. 001),达到或超过假手术组。PTH和Alen组各部位BMD无明显差别。A+P组腰椎BMD高于PTH组(P<0. 05),股骨BMD明显高于PTH及Alen组(均

Effects of teriparatide and alendronate on bone mineral density of osteoporotic rats

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.