Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna, Vienna, Austria.
Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Vienna, Austria.
Ann Rheum Dis. 2019 Dec;78(12):1706-1711. doi: 10.1136/annrheumdis-2019-215714. Epub 2019 Sep 26.
Whether HMG-CoA-reductase inhibition, the main mechanism of statins, plays a role in the pathogenesis of osteoporosis, is not entirely known so far. Consequently, this study was set out to investigate the relationship of different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis.
Medical claims data of all Austrians from 2006 to 2007 was used to identify all patients treated with statins to compute their daily defined dose averages of six different types of statins. We applied multiple logistic regression to analyse the dose-dependent risks of being diagnosed with osteoporosis for each statin individually.
In the general study population, statin treatment was associated with an overrepresentation of diagnosed osteoporosis compared with controls (OR: 3.62, 95% CI 3.55 to 3.69, p<0.01). There was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis. Osteoporosis was underrepresented in low-dose statin treatment (0-10 mg per day), including lovastatin (OR: 0.39, CI 0.18 to 0.84, p<0.05), pravastatin (OR: 0.68, 95% CI 0.52 to 0.89, p<0.01), simvastatin (OR: 0.70, 95% CI 0.56 to 0.86, p<0.01) and rosuvastatin (OR: 0.69, 95% CI 0.55 to 0.87, p<0.01). However, the exceeding of the 40 mg threshold for simvastatin (OR: 1.64, 95% CI 1.31 to 2.07, p<0.01), and the exceeding of a 20 mg threshold for atorvastatin (OR: 1.78, 95% CI 1.41 to 2.23, p<0.01) and for rosuvastatin (OR: 2.04, 95% CI 1.31 to 3.18, p<0.01) was related to an overrepresentation of osteoporosis.
Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose and overrepresented in high-dose statin treatment, demonstrating the importance of future studies' taking dose-dependency into account when investigating the relationship between statins and osteoporosis.
目前尚不完全清楚羟甲基戊二酰辅酶 A 还原酶抑制剂（他汀类药物的主要作用机制）是否在骨质疏松症的发病机制中发挥作用。因此，本研究旨在调查不同种类和剂量的他汀类药物与骨质疏松症之间的关系，并假设胆固醇合成的抑制可能会影响性激素，从而影响骨质疏松症的诊断。
使用 2006 年至 2007 年所有奥地利人的医疗索赔数据，确定所有接受他汀类药物治疗的患者，计算他们使用六种不同类型他汀类药物的平均日剂量。我们应用多变量逻辑回归分析每种他汀类药物剂量依赖性骨质疏松症诊断风险。
在一般研究人群中，与对照组相比，他汀类药物治疗与骨质疏松症的诊断存在显著相关性（OR：3.62，95%CI 3.55 至 3.69，p<0.01）。他汀类药物剂量与 OR 值之间存在高度非平凡的依赖性。在低剂量他汀类药物治疗（每天 0-10mg）中，骨质疏松症的代表性不足，包括洛伐他汀（OR：0.39，CI 0.18 至 0.84，p<0.05）、普伐他汀（OR：0.68，95%CI 0.52 至 0.89，p<0.01）、辛伐他汀（OR：0.70，95%CI 0.56 至 0.86，p<0.01）和罗苏伐他汀（OR：0.69，95%CI 0.55 至 0.87，p<0.01）。然而，当辛伐他汀的剂量超过 40mg 时（OR：1.64，95%CI 1.31 至 2.07，p<0.01），以及阿托伐他汀（OR：1.78，95%CI 1.41 至 2.23，p<0.01）和罗苏伐他汀（OR：2.04，95%CI 1.31 至 3.18，p<0.01）的剂量超过 20mg 时，骨质疏松症的诊断率也会升高。
我们的结果表明，他汀类药物治疗患者的骨质疏松症诊断与剂量有关。因此，低剂量他汀类药物治疗骨质疏松症的代表性不足，而高剂量他汀类药物治疗骨质疏松症的代表性过高，这表明未来研究在研究他汀类药物与骨质疏松症之间的关系时，应考虑剂量依赖性。
