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目的观察重组人甲状旁腺素(1-34)[rhPTH(1-34)]对绝经后骨质疏松患者血清基质金属蛋白酶1(MMP-1)及其组织抑制因子(TIMP-1)水平的影响,探讨其调节骨代谢的机制。方法绝经后女性90名分为骨质疏松组和正常组,骨质疏松组每日皮下注射rhPTH(1-34)20μg+钙剂600 mg+维生素D_3 200 IU,正常组不给予任何药物干预。检测腰椎骨密度(BMD),血钙、磷、MMP-1、TIMP-1、内源性全段甲状旁腺素(iPTH)、骨特异性碱性磷酸酶(BSAP)以及尿Ⅰ型胶原交联氨基末端肽(NTX)水平,并分析参数之间的相关关系。结果正常组BMD、血钙高于骨质疏松组(p<0.01),而iPTH、BSAP、MMP-1和尿NTX低于骨质疏松组(P<0.05)。rhPTH(1-34)治疗后,骨质疏松组患者腰椎BMD,血钙、磷、MMP-1、BSAP和尿NTX增高,而iPTH下降,与治疗前相比差异显著(P<0.05)。血TIMP-1与腰椎BMD成负相关(r=-0.376,P=0.014),校正年龄、体重指数后关系仍然存在;MMP-1与其他指标没有相关性。结论小剂量rhPTH(1-34)可促进绝经后骨质疏松患者血MMP-1水平增高,从而使成骨活性增强,这可能是其促进骨形成的机制之一。
Objective To observe the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)] on the serum levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase (TIMP-1) in postmenopausal osteoporosis patients Influence, explore its mechanism of regulating bone metabolism. Methods 90 postmenopausal women were divided into osteoporosis group and normal group. In the osteoporosis group, rhPTH (1-34) 20 μg and calcium 600 mg + vitamin D_3 200 IU were injected into the osteoporosis group daily without any drug intervention. The bone mineral density (BMD), serum calcium, phosphorus, MMP-1, TIMP-1, iPTH, BSAP and urinary type Ⅰ collagen The level of N-terminal peptide (NTX) was analyzed and the correlation between parameters was analyzed. Results The serum levels of BMD and serum calcium in normal group were significantly higher than those in osteoporosis group (p <0.01), while those in iPTH, BSAP, MMP-1 and NTX were lower than those in osteoporosis group (P <0.05). After treatment with rhPTH (1-34), BMD, serum calcium, phosphorus, MMP-1, BSAP and urinary NTX in osteoporosis group increased and iPTH decreased significantly compared with those before treatment (P <0.05). TIMP-1 was negatively correlated with BMD of lumbar spine (r = -0.376, P = 0.014). The relationship between serum TIMP-1 and BMD was still existed after correction for age and body mass index. There was no correlation between MMP-1 and other indexes. Conclusion Low dose of rhPTH (1-34) can promote the increase of serum MMP-1 level in postmenopausal osteoporosis patients, leading to the enhancement of osteogenic activity, which may be one of the mechanisms that promote osteogenesis.