Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Osteoporos Int. 2011 Mar;22(3):993-1001. doi: 10.1007/s00198-010-1512-y. Epub 2010 Dec 17.
Prior studies have suggested an association between bisphosphonate use and subtrochanteric fractures. This cohort study showed an increased risk of subtrochanteric and femoral shaft fractures both before and after the start of drugs against osteoporosis including bisphosphonates. This may suggest an effect of the underlying disease rather than the drugs used.
The objective of this study is to determine the association between drugs against osteoporosis and the risk of femoral shaft and subtrochanteric fractures. No separation was made between atypical and typical fractures.
Nationwide cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as exposed group and three age- and gender-matched controls from the general population (n = 310,683). Adjustments were made for prior fracture, use of systemic hormone therapy, and use of systemic corticosteroids.
After initiation of therapy, an increased risk of subtrochanteric fractures was seen for alendronate (hazard ratio (HR) = 2.41, 95% confidence interval (CI) 1.78-3.27), etidronate (HR = 1.96, 95% CI 1.62-2.36), and clodronate (HR = 20.0, 95% CI 1.94-205), but not for raloxifene (HR = 1.06, 95% CI 0.34-3.32). However, an increased risk of subtrochanteric fractures was also present before the start of alendronate (OR = 2.36, 95% CI 2.05-2.72), etidronate (OR = 3.05, 95% CI 2.59-3.58), clodronate (OR = 10.8, 95% CI 1.14-103), raloxifene (OR = 1.90, 95% CI 1.07-3.40), and strontium ranelate (OR = 2.97, 95% CI 1.07-8.27). Similar trends were seen for femoral shaft fractures and overall fracture risk. After the start of etidronate, no dose-response relationship was present (p for trend, 0.54). For alendronate, a decreasing risk was present with increasing average daily dose (p for trend, <0.01).
Although an increased risk of femoral shaft and subtrochanteric fractures are seen with the use of several types of bisphosphonates, the increased risk before the start of the drugs may point at an effect of the underlying disease being treated. The increased risk may, thus, perhaps be due to confounding by indication.
本研究旨在确定骨质疏松症治疗药物与股骨干和转子下骨折风险之间的关联。未对非典型和典型骨折进行区分。
这是一项来自丹麦的全国性队列研究，纳入了 1996 年至 2006 年间使用双膦酸盐和其他骨质疏松症治疗药物的所有患者（n=103562）作为暴露组，以及来自普通人群的 3 名年龄和性别匹配的对照组（n=310683）。对既往骨折、全身激素治疗和全身皮质类固醇治疗的使用情况进行了调整。
在开始治疗后，阿仑膦酸钠（HR=2.41，95%CI 1.78-3.27）、依替膦酸钠（HR=1.96，95%CI 1.62-2.36）和氯屈膦酸钠（HR=20.0，95%CI 1.94-205）的转子下骨折风险增加，但雷洛昔芬（HR=1.06，95%CI 0.34-3.32）的风险未增加。然而，在开始使用阿仑膦酸钠之前（OR=2.36，95%CI 2.05-2.72）、依替膦酸钠（OR=3.05，95%CI 2.59-3.58）、氯屈膦酸钠（OR=10.8，95%CI 1.14-103）、雷洛昔芬（OR=1.90，95%CI 1.07-3.40）和雷奈酸锶（OR=2.97，95%CI 1.07-8.27），转子下骨折的风险也增加。股骨干骨折和总体骨折风险也存在类似的趋势。开始使用依替膦酸钠后，无剂量-反应关系（趋势检验的 p 值为 0.54）。对于阿仑膦酸钠，随着平均日剂量的增加，风险呈下降趋势（趋势检验的 p 值<0.01）。
尽管使用多种类型的双膦酸盐会增加股骨干和转子下骨折的风险，但在开始使用药物之前风险的增加可能表明正在治疗的基础疾病的影响。因此，增加的风险可能是由于混杂因素所致。
