Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study.
Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study.
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髋关节，下调和股骨轴骨折的风险在Alendronate的长期和长期使用者中：全国性队列和嵌套的病例对照研究。
DOI：
10.1136/bmj.i3365
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发表时间：
2016-06-28
期刊：
影响因子：
--
通讯作者：
Eastell R
中科院分区：
文献类型：
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作者：
Abrahamsen B;Eiken P;Prieto-Alhambra D;Eastell R
目的 确定骨质疏松症患者长期（≥10 年）使用阿仑膦酸钠的骨骼安全性和有效性。设计基于开放登记的队列研究，其中包含两项嵌套病例对照研究。设置对丹麦人口的全国性研究。参与者 61 990 名在治疗开始时年龄为 50-94 岁的男性和女性，他们之前没有服用过阿仑膦酸钠，1996-2007 年。干预措施 使用阿仑膦酸钠治疗。主要结果指标是股骨粗隆下或股骨干 (ST/FS) 或髋部发生骨折。队列中的非骨折对照按性别、出生年份和开始阿仑膦酸钠治疗的年份与骨折病例进行匹配。拟合条件逻辑回归模型来计算在调整和不调整合并症和并发症的情况下的比值比。敏感性分析调查了其他骨质疏松药物的后续治疗。结果 1428 名参与者出现 ST/FS（发病率 3.4/1000 人年，95% 置信区间 3.2 至 3.6），6784 名参与者出现髋部骨折（16.2/1000 人年，15.8 至 16.6）。与阿仑膦酸钠治疗依从性高（药物持有率（MPR，依从性指标）>80%）相比，依从性差（MPR <50%；比值比 0.88、0.77 至 0.99；P=0.05）的 ST/FS 风险较低。多变量调整减弱了这种关联（调整后的优势比为 0.88、0.77 至 1.01；P=0.08）。与过去使用者相比，长期使用者（≥10个剂量年；0.70，0.44至1.11；P=0.13）或当前使用者的风险并不较高（0.91，0.79至1.06；P=0.22）。同样，MPR>80%与髋部骨折风险降低相关（0.73，0.68至0.78；P<0.001），长期累积使用5-10个剂量年（0.74，0.67至0.83；P<0.001）或≥10个剂量年（0.74，0.56至0.97；P=0.03）也是如此。结论 这些发现支持阿仑膦酸钠治疗在骨折结局方面的获益与风险之间存在可接受的平衡，即使连续使用 10 多年也是如此。
Objectives To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis. Design Open register based cohort study containing two nested case control studies. Setting Nationwide study of population of Denmark. Participants 61 990 men and women aged 50-94 at the start of treatment, who had not previously taken alendronate, 1996-2007. Interventions Treatment with alendronate. Main outcome measures Incident fracture of the subtrochanteric femur or femoral shaft (ST/FS) or the hip. Non-fracture controls from the cohort were matched to fracture cases by sex, year of birth, and year of initiation of alendronate treatment. Conditional logistic regression models were fitted to calculate odds ratios with and without adjustment for comorbidity and comedications. Sensitivity analyses investigated subsequent treatment with other drugs for osteoporosis. Results 1428 participants sustained a ST/FS (incidence rate 3.4/1000 person years, 95% confidence interval 3.2 to 3.6), and 6784 sustained a hip fracture (16.2/1000 person years, 15.8 to 16.6). The risk of ST/FS was lower with high adherence to treatment with alendronate (medication possession ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR <50%; odds ratio 0.88, 0.77 to 0.99; P=0.05). Multivariable adjustment attenuated this association (adjusted odds ratio 0.88, 0.77 to 1.01; P=0.08). The risk was no higher in long term users (≥10 dose years; 0.70, 0.44 to 1.11; P=0.13) or in current compared with past users (0.91, 0.79 to 1.06; P=0.22). Similarly, MPR >80% was associated with a decreased risk of hip fracture (0.73, 0.68 to 0.78; P<0.001) as was longer term cumulative use for 5-10 dose years (0.74, 0.67 to 0.83; P<0.001) or ≥10 dose years (0.74, 0.56 to 0.97; P=0.03). Conclusions These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use.