The Osteoporosis Clinic, Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital THG, Tage Hansens Gade 2, 8000 Aarhus C, Denmark.
Calcif Tissue Int. 2012 Jan;90(1):22-9. doi: 10.1007/s00223-011-9549-2. Epub 2011 Nov 26.
We studied the association between bisphosphonate use and risk of acute myocardial infarction (AMI) or atherosclerosis of the coronary vessels using a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) comprised the exposed group and three age- and gender-matched controls from the general population (n = 310,683), the unexposed group. The main outcomes were occurrence of AMI or atherosclerosis of the coronary vessels. An excess risk of AMI was seen in users of alendronate compared to the unexposed. However, an inverse dose-response relationship was seen, with an increased risk in those with low adherence (≤0.66 DDD, HR = 1.50, 95% CI 1.24-1.82) and a nonsignificantly decreased risk in those who were adherent to the drug (≥1 DDD, HR = 0.80, 95% CI 0.59-1.09; P for trend <0.01). For etidronate and raloxifene, no excess risk was present and no dose-response relationship was seen. For atherosclerosis of the coronary vessels, a similar trend as for AMI was seen for alendronate but a protective effect was present at high doses (≥1 DDD, HR = 0.58, 95% CI 0.49-0.70). For etidronate, an increased risk of atherosclerosis was seen at all doses, with no dose-response relationship. For raloxifene, no excess of atherosclerosis was observed. At high doses of alendronate a decreased risk of atherosclerosis of the coronary vessels was seemingly present, whereas at low doses an increased risk was present. The finding may be spurious due to the "healthy user" effect, but a causal relationship cannot be excluded.
我们使用丹麦全国性回顾性队列研究，研究了双膦酸盐的使用与急性心肌梗死（AMI）或冠状动脉粥样硬化的风险之间的关系。1996 年至 2006 年期间所有使用双膦酸盐和其他骨质疏松症药物的患者（n=103562）构成暴露组，来自普通人群的 310683 名年龄和性别匹配的患者（n=310683）为未暴露组。主要结局为 AMI 或冠状动脉粥样硬化的发生。与未暴露组相比，阿仑膦酸盐使用者发生 AMI 的风险增加。然而，存在着一种剂量-反应关系，低依从性（≤0.66 DDD，HR=1.50，95%CI 1.24-1.82）的患者风险增加，而依从性好的患者（≥1 DDD，HR=0.80，95%CI 0.59-1.09；P 趋势<0.01）风险降低不显著。对于依替膦酸和雷洛昔芬，没有发现风险增加，也没有剂量-反应关系。对于冠状动脉粥样硬化，阿仑膦酸盐的趋势与 AMI 相似，但高剂量（≥1 DDD，HR=0.58，95%CI 0.49-0.70）存在保护作用。对于依替膦酸，所有剂量下的冠状动脉粥样硬化风险均增加，没有剂量-反应关系。对于雷洛昔芬，没有观察到冠状动脉粥样硬化的增加。高剂量的阿仑膦酸盐似乎降低了冠状动脉粥样硬化的风险，而低剂量则增加了风险。由于“健康使用者”效应，这一发现可能是虚假的，但不能排除因果关系。
