摘要
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。
AIM To investigate the effects of recombinant human parathyroid hormone（1 -34）（rhPTH （1-34）） on the serum matrix metalloproteinase 1（MMP-1） and tissue inhibitor of metalloproteinase 1（TIMP- 1） in postmenopausal women with osteoporosis,and evaluate the mechanism of it on regulating the anabolic response of the skeleton.METHODS Ninety postmenopausal women were divided into osteoporosis group and normal group.Patients in the osteoporosis group were treated with subcutaneous rhPTH（1-34） 20μg plus oral elemental calcium 600 mg and vitamin D_3 200 IU,and patients in the normal group did not receive any medications.The bone mineral density（BMD） of the lumbar spine,the serum levels of calcium（Ca）, phosphate（P）,MMP-1,TIMP-1,endogenous intact PTH（iPTH）,bone-specific alkaline phosphatase （BSAP） and the level of urine cross linked N-telopeptide of typeⅠcollagen（NTX） were measured.The associations between the parameters were also analyzed.RESULTS It showed that serum Ca and the BMD of the normal group were higher than the osteoporosis group（P0.01）,but the levels of serum iPTH,BSAP,MMP- 1 and urine NTX were lower than the osteoporosis group（P0.05）.After the treatment of rhPTH（1-34）, the BMD and the levels of serum Ca,P,MMP-1,BSAP and urine NTX were increased,on the contrary,the iPTH were decreased（P0.05） in the osteoporosis group.In all elderly women,serum TIMP-1 negatively correlated with BMD（r = -0.376,P = 0.014）,the correction remained after adjusting for age and body mass index（BMI）,the serum MMP-1 had no associations with other parameters.CONCLUSION The intermittent injections of rhPTH（1-34） are able to stimulate bone formation and improve the ability of osteoblasts.The increase of serum MMP-1 maybe plays a positive effect on anabolic effect of PTH.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2011年第1期20-23,共4页
Chinese Journal of New Drugs and Clinical Remedies
