唑来膦酸治疗原发性骨质疏松症用药后急性期发热反应的相关危险因素分析

Risk Factors for Acute Febrile Reaction after Zoledronic Acid Treatment for Primary Osteoporosis

目的:探讨唑来膦酸治疗原发性骨质疏松症出现急性期发热反应的特点及相关影响因素。方法:收集中国医科大学附属盛京医院2012年1月—2020年12月诊断为原发性骨质疏松症并给予唑来膦酸治疗的患者517例,其中男40例,女477例;Ⅰ型患者262例,Ⅱ型患者255例;轻、中度骨质疏松患者245例,重度骨质疏松患者272例;新发骨折患者230例,手术患者209例。对收集的2组资料进行比较,归纳分析发热的临床特点,并分别从性别、年龄、白细胞、中性粒细胞、淋巴细胞、中性粒细胞淋巴细胞比值(NLR)、骨质疏松类型、骨质疏松程度、有无骨折、有无手术、用药史等方面行单因素分析,研究其与发热反应的相关性,进一步行Logistic多因素回归分析,绘制ROC曲线,探讨发热不良反应的主要影响因素。结果:517例患者中175例(33.85%)出现急性期发热反应,多数发生在用药后36 h以内,以低中热(<39℃)为主,持续时间一般不超过60 h。单因素分析显示发热组与不发热组之间NLR、骨质疏松类型、程度、新发骨折、手术及唑来膦酸用药史的差异有统计学意义(P<0.05)。2组间性别、用药前白细胞、中性粒细胞、淋巴细胞差异无统计学意义(P>0.05)。Logistic多因素回归、ROC曲线分析进一步显示手术组发热率较高(P<0.01,ROC曲线下面积为0.65),骨折组发热率较高(P<0.05,ROC曲线下面积为0.60),Ⅰ型骨质疏松组发热率较高(P<0.01,ROC曲线下面积为0.44),既往有唑来膦酸用药史组发热率较低(P<0.01,ROC曲线下面积为0.34)。关节骨折手术组发热率(56.60%)明显高于脊柱骨折手术组发热率(38.54%)(P<0.05)。结论:唑来膦酸治疗原发性骨质疏松症时,急性发热反应率为33.85%,手术、骨折、Ⅰ型骨质疏松症和首次唑来膦酸治疗可能是独立的危险因素,手术患者(尤其是关节骨折手术)、新鲜骨折、Ⅰ型骨质疏松及首次唑来膦酸用药的患者急性发热反应风险更高。

Objective:To investigate the characteristics and risk factors of acute febrile reaction after zoledronic acid treatment for primary osteoporosis.Methods:A total of 517 patients diagnosed with primary osteoporosis and treated with zoledronic acid from January 2012 to December 2020 were recruited,including 40 males and 477 females,among whom 262 were with typeⅠosteoporosis and 255 were with typeⅡosteoposis,245 pa-t ients with mild-to-moderate osteoporosis,272 patients with severe osteoporosis,230 patients with fresh fracture,and 209 patients with operation.The two groups were compared,and the fever rate and clinical characteristics of fever were summarized and further analyzed in the aspects of gender,age,count of white blood cells,neutrophils,lymphocytes,neutrophil-lymphocyte ratio(NLR),type of osteoporosis,degree of osteoporosis,fracture,surgery intervention,medication history,etc.Multivariate Logistic regression analysis was conducted and ROC curve was drawn to explore the main risk factors for acute febrile reaction.Results:The 175 cases(33.85%)developed acute febrile reaction,most of which occurred within 36 hours after treatment,mainly low and moderate fever(<39℃),a nd the duration was generally no more than 60 hours.Univariate analysis showed significant differences in NLR,type and degree of osteoporosis,fresh fracture,surgery intervention,and zoledronic acid medication history between the fever and non-fever groups(P<0.05).There was no significant difference in gender,count of white blood cells,neutrophils and lymphocytes between the two groups(P>0.05).Logistic regression and ROC curve analysis showed that the surgery group had a higher fever rate(P<0.01,area under ROC curve was 0.65).The fracture group had a higher fever rate(P<0.05,area under ROC curve was 0.60).The group with typeⅠosteopo-r osis had a higher fever rate(P<0.01,area under ROC curve was 0.44).The group with medication history had a lower fever rate(P<0.01,area under ROC curve was 0.34).The fever rate of joint fracture group(56.60%)was significantly higher than spine fracture group(38.54%)(P<0.05).Conclusion:Surgery,fracture,typeⅠosteopo-r osis and first zoledronic acid medication might be independent risk factors of acute febrile reaction after medication.Patients who had surgery before medication(especially those with joint fracture surgery),fresh fracture,typeⅠosteoporosis and first zoledronic acid medication,had a higher risk of acute febrile reaction.