Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates.
Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates.
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DOI：
10.1056/nejmoa1916525
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发表时间：
2020-08-20
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双膦酸盐可有效减少髋部骨折和骨质疏松性骨折。然而，对非典型股骨骨折的担忧导致双膦酸盐的使用大幅减少，髋部骨折的发生率可能正在增加。关于非典型股骨骨折与双膦酸盐和其他危险因素之间的关系仍存在重要的不确定性。我们研究了50岁或50岁以上接受双膦酸盐治疗的妇女，她们在凯撒永久医疗机构南加州医疗保健系统登记；这些女性从2007年1月1日到2017年11月30日被跟踪调查。主要结局为非典型股骨骨折。有关风险因素的数据，包括双膦酸盐的使用，是从电子健康记录中获得的。骨折用x线片确定。采用多变量Cox模型。对使用双膦酸盐1 - 10年的风险-收益曲线进行建模，以比较相关的非典型骨折和其他预防的骨折。在196129名女性中，发生了277例非典型股骨骨折。多变量调整后，非典型骨折的风险随着双膦酸盐使用时间的延长而增加：与少于3个月的患者相比，3年至5年的风险比从8.86（95%可信区间[CI]， 2.79至28.20）增加到8年或更长时间的43.51 （95% CI， 13.70至138.15）。其他危险因素包括种族（亚洲人与白人的危险比为4.84；95% CI为3.57至6.56）、身高、体重和糖皮质激素的使用。停用双膦酸盐与非典型骨折风险的快速降低有关。在使用双膦酸盐的1 - 10年间，骨质疏松症和髋部骨折风险的降低远远超过了白人非典型骨折风险的增加，但在亚洲人中则较少。3年后，白人预防了149例髋部骨折，2例发生了双磷酸盐相关的非典型骨折，而亚洲人分别为91例和8例。非典型股骨骨折的风险随着双膦酸盐使用时间的延长而增加，在双膦酸盐停药后迅速降低。亚洲人的患病风险高于白人。与双膦酸盐治疗髋部和其他骨折的风险降低相比，非典型股骨骨折的绝对风险仍然非常低。（由Kaiser Permanente等机构资助。）
Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors. We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk–benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented. Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians. The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.)