【摘要】 目的研究口服阿仑膦酸钠维D₃或单次肌肉注射维生素D₂预处理对首次静脉注射唑来膦酸治疗骨质疏松症发生急性时相反应的影响。方法选取绝经后骨质疏松症患者97例,随机纳入口服阿仑膦酸钠维D₃处理组（阿仑组,33例）、单次肌肉注射维生素D₂组（VD₂组,31例）、无预处理组（对照组,33例）,比较分析3组的临床资料、基线指标及静脉注射唑来膦酸前后血常规、生化指标及72 h内急性时相反应发生率。采用多元Logistic回归分析探讨发热与血常规、生化指标、骨转换指标的相关性。结果 3组患者年龄、体重及基线血常规、生化指标均无明显差异（均P>0.05）。单因素方差分析（One-way ANOVA）对比三组患者静脉注射唑来膦酸前后血常规及生化指标,VD₂组及阿仑组中性粒细胞/淋巴细胞比值（neutrohpil to lymphocyte ratio,NRL）均小于对照组,差异均有统计学意义（P<0.05）。静脉输注唑来膦酸后72 h内对照组、VD₂组、阿仑组急性时相反应发生率分别为:发热（81.8%,74.2%,41.9%）、乏力（45.5%,9.7%,12.9%）、头痛（60.6%,19.4%,6.5%）、头晕（21.2%,9.7%,0%）、骨痛（69.7%,45.2%,16.1%）、关节痛（54.5%,6.5%,12.9%）、肌肉痛（63.6%,38.7%,22.6%）及恶心（15.2%,3.2%,0%）,差异均有统计学意义（均P<0.05）,VD₂组及阿仑组上述症状发生率均较对照组低。经Pearson相关性分析发现发热与用药前总I型前胶原氨基端延长肽（total procollagen type 1 amino-terminal propeptide,t P1NP）及I型胶原羧基端肽β特殊序列（β-isomerized C-terminal telopeptide of type I collagen,β-CTX）呈显著正相关（相关系数分别为0.28和0.29,P均<0.05）,与25羟维生素D [25-OH vitamin D,25 （OH） D]呈显著负相关（相关系数为-0.36,P<0.05）。多元Logistic回归分析表明用药前血清25 （OH） D低水平为用药后发生发热的危险因素[OR=0.86 （95%CI:0.72～0.90）,P=0.04]。结论阿仑膦酸钠维D₃及维生素D₂预处理均可有效缓解首次静脉注射唑来膦酸出现的急性时相反应,用药前血清25 （OH） D低水平可作为静脉注射唑来膦酸后发热的危险因素。更多还原

【Abstract】 Objective To investigate the efficacy of alleviation of acute phase reaction（APR） after zoledronic acid infusion pretreated with oral bisphosphonates or vitamin D₂ intramuscular injection compare with control in osteoporosis patients.Methods A total of 97 osteoporosis postmenopausal women undergoing their first zoledronic acid（ZOL） infusion were involved.They received randomly with oral bisphosphonates 4 weeks（33 patients）,vitamin D₂ intramuscular injection single dose（31 patients）,and blank control（33 patients） before the ZOL infusion.We compared the differences among the three groups for APR in 72 hours,blood routine,blood biochemical markers.The multi-factors logistic regression analysis was used to identify the potential influencing factors for fever.Results It had no significant difference of general characteristics,blood routine,and blood biochemical indicators before ZOL infusion among the three groups.One-way ANOVA showed that neutrohpil to lymphocyte ratio（NRL） of two groups pretreated with oral bisphosphonates or vitamin D₂ intramuscular injection were lower than control group after ZOL infusion（P < 0.05）.The APR incidence of the three group（control,oral bisphosphonates,vitamin D₂ intramuscular injection） were as below:fever（81.8%, 74.2%, 41.9%）,fatigue（45.5%, 9.7%, 12.9%）,headache（60.6%, 19.4%, 6.5%）,dizzy（21.2%, 9.7%, 0%）,bone pain（69.7%, 45.2%, 16.1%）,joint pain（54.5%, 6.5%, 12.9%）,muscleache（63.6%,38.7%,22.6%）,and nausea（15.2%,3.2%,0%）.The difference among the three group was statistically significant（all P < 0.05）.Pearson correlation analysis revealed that fever was significantly positively correlated with total procollagen type 1 amino-terminal propeptide（t P1 NP） and β-isomerized C-terminal telopeptide of type Ⅰ collagen（β-CTX） level before ZOL infusion（correlation coefficients: 0.28 and 0.29,P< 0.05）,and was significantly negatively correlated with 25-OH vitamin D [25（OH）D] level before ZOL infusion（correlation coefficient:-0.36,P< 0.05）.Multi-factors Logistic regression analysis showed that the OR of 25（OH） D level was 0.86（95% CI: 0.72-0.90,P< 0.05）,implying lower levels of 25（OH） D was a risk factor of fever.Conclusions Both of oral bisphosphonates and vitamin D₂ intramuscular injection pretreated groups have the efficacy of alleviation of APR after ZOL infusion.Lower levels of 25（OH） D is a risk factor of fever after ZOL infusion.更多还原