阿仑膦酸钠治疗原发性骨质疏松症的长期疗效及安全性分析

The efficacy and safety of long-term use of alendronate in primary osteoporosis

目的回顾性分析口服阿仑膦酸钠治疗原发性骨质疏松症的长期临床疗效及安全性,探讨药物假期开展的必要性。方法从2010年1月至2016年12月在中国人民解放军南部战区总医院就诊的原发性骨质疏松症患者中筛选出接受阿仑膦酸(70 mg/周)治疗至少3年的患者53例作为研究对象,所有患者均给予维生素D和钙片作为基础治疗。采集所有患者基线及1、2、3、4、5、6年腰椎L1~4、股骨颈和全髋关节骨密度(bone mineral density,BMD),血清I型原胶原N-端前肽(procollagen type1 N-peptide,P1NP),β-I型胶原羧基端肽(β-胶原降解产物)(β-isomerized carboxy-telopeptide of type I collagen,β-CTX)等资料,将药物治疗后与基线水平进行比较。结果纳入研究的患者平均年龄(75.85±10.67)岁,平均用药年限为(4.83±1.54)年,最长可达7年。腰椎BMD第5年增长12.579%,并且与基线相比差异有统计学意义(P<0.05);股骨颈BMD在第3年增长3.516%,第6年为-4.791%;全髋关节BMD在第3年增长最多为6.676%,第6年为-1.157%。P1NP、β-CTX等骨转换标志物水平随着用药年限的增加,下降的幅度减小,甚至有上升的趋势,第0.25、0.5、1、2、3年的P1NP与基线相比差异均有统计学意义(P<0.05)。4人用药期间出现脆性骨折,脆性骨折发生率为7.54%,1人存在骨折愈合延迟。结论阿仑膦酸钠治疗原发性骨质疏松症的疗效在连续用药3~5年时间内是稳步上升或较为稳定,但在用药3~5年后会有明显下降趋势,并有可能增加罕见不良反应的发生率,可见对长期使用阿仑膦酸的患者开展药物假期具有必要性。

Objective A retrospective study on the effectiveness and safety of alendronate( ALN) treatment in primary osteoporosis was carried out to explore the necessity of a drug holiday for long-term use of ALN.Methods Medical records of fifty-three primary osteoporosis patients receiving ALN treatment( 70 mg,once a week,at least 3 years) from Jan 2010 to Dec 2016 were retrospectively analyzed.Simultaneously,all of them were given vitamin D and calcium as a basic treatment.The bone densitometry of lumbar spine L1-4,femoral neck and total hip and bone turnover markers such as P1NP and β-CTX level were measured at baseline and after 1,2,3,4,5 and 6 years of treatment,respectively.Results The average age of patients was( 75.85±10.67) years,the average duration of medication was( 4.83±1.54) years,and the longest duration reached 7 years.After 5 years of treatment,the BMD of lumbar spine L1-4 had the biggest rise compared with the baseline level(+12.579%),and the difference was statistically significant( P<0.05).After 3 years of treatment,the BMD of femoral neck and total hip had the biggest rise compared with the baseline level(+3.516%) and(+6.676%),respectively,but both of them declined in the sixth year(-4.791%) and(-1.157%),respectively.As the time of ALN use increased,the decrease in the levels of bone turnover markers such as P1 NP and β-CTX slowed down,or even had a trend of increase.The levels of P1NP at 0.25,0.5,1,2 and 3 years were all significantly different from the baseline level( P < 0.05).Four patients had fragility fractures during the treatment,and the incidence of brittle fracture was 7.54%.One person had delayed fracture healing.Conclusion The effectiveness of ALN in the treatment of POP was steadily increasing or stable for 3 to 5 years of continuous medication,but it decreased significantly after 3 to 5 years of treatment.The incidence of rare adverse reactions would increase after long term use of ALN.Therefore,it is necessary to carry out a drug holiday in patients with long-term use of alendronate.