Abstract：
BACKGROUND: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF).
OBJECTIVE: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined.
METHODS: Population-based case-cohort study.
METHODS: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images.
METHODS: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021).
METHODS: Bisphosphonate use was collected from 1995-2015.
METHODS: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10.
RESULTS: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure.
CONCLUSIONS: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.
OBJECTIVE: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined.
METHODS: Population-based case-cohort study.
METHODS: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images.
METHODS: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021).
METHODS: Bisphosphonate use was collected from 1995-2015.
METHODS: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10.
RESULTS: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure.
CONCLUSIONS: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.
摘要：
背景：长期双膦酸盐（BP）治疗骨质疏松症可预防髋部和其他骨折，但可导致非典型股骨骨折（AFF）。
目的：建立BP使用模式与AFF和髋部骨折风险之间的关系。还检查了AFF的其他潜在风险因素。
方法：基于人群的病例队列研究。
方法：丹麦国家医疗保健系统保持药物使用的纵向记录，医疗保健利用，和X射线图像。
方法：在所有190万≥50岁的丹麦成年人中，对2010-2015年之间的股骨转子下或股骨干骨折（n=4,973）进行了鉴定，并与随机样本进行了比较（n=37,021）。
方法：收集了1995-2015年的双膦酸盐使用情况。
方法：由盲法研究放射科医师审查骨折X线片（n=4,769），以使用既定标准鉴定AFF（n=181）。通过ICD-10鉴定了随机样本中的传统髋部骨折（n=691）。
结果：与<1年的BP使用相比，使用5-7年与AFF增加7倍相关[调整后的HR=7.29(CI:3.07,17.30)];停药后AFF的风险迅速下降。一个AFF需要的5年伤害人数为1,424，而预防一个髋部骨折需要的5年治疗人数为56。糖皮质激素和质子泵抑制剂的使用与AFF风险增加独立相关。有AFF的人中有31％没有BP暴露。
结论：AFF的风险随着使用BP的持续时间而增加，但在≥50岁的成年人中，BP治疗的有益效果明显超过这种增加的风险。近三分之一的AFF患者没有BP暴露。
目的：建立BP使用模式与AFF和髋部骨折风险之间的关系。还检查了AFF的其他潜在风险因素。
方法：基于人群的病例队列研究。
方法：丹麦国家医疗保健系统保持药物使用的纵向记录，医疗保健利用，和X射线图像。
方法：在所有190万≥50岁的丹麦成年人中，对2010-2015年之间的股骨转子下或股骨干骨折（n=4,973）进行了鉴定，并与随机样本进行了比较（n=37,021）。
方法：收集了1995-2015年的双膦酸盐使用情况。
方法：由盲法研究放射科医师审查骨折X线片（n=4,769），以使用既定标准鉴定AFF（n=181）。通过ICD-10鉴定了随机样本中的传统髋部骨折（n=691）。
结果：与<1年的BP使用相比，使用5-7年与AFF增加7倍相关[调整后的HR=7.29(CI:3.07,17.30)];停药后AFF的风险迅速下降。一个AFF需要的5年伤害人数为1,424，而预防一个髋部骨折需要的5年治疗人数为56。糖皮质激素和质子泵抑制剂的使用与AFF风险增加独立相关。有AFF的人中有31％没有BP暴露。
结论：AFF的风险随着使用BP的持续时间而增加，但在≥50岁的成年人中，BP治疗的有益效果明显超过这种增加的风险。近三分之一的AFF患者没有BP暴露。
