Sgadari A, Lapane K L, Mor V, Landi F, Bernabei R, Gambassi G
Istituto di Medicina Interna e Geriatria, Università Cattolica del Sacro Cuore, Rome, Italy.
J Clin Psychopharmacol. 2000 Apr;20(2):234-9. doi: 10.1097/00004714-200004000-00017.
Benzodiazepine use is a well-identified risk factor for falls and the resulting femur fractures in elderly adults. Benzodiazepines not requiring hepatic biotransformation may be safer than agents undergoing oxidation because oxidative activity has been shown to decline with age. The association between the use of either oxidative or nonoxidative benzodiazepines and the risk of femur fracture among elderly adults living in nursing homes was studied. A nested case-control study was conducted using the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database; the records of 9,752 patients hospitalized for incident femur fracture during the period 1992 to 1996 were extracted, matching by age, gender, state, and index date to the records of 38,564 control patients. Conditional logistic regression models were conducted to estimate the odds ratios (ORs) for femur fracture with adjustment for potential confounders. The adjusted OR for the overall use of benzodiazepines was 1.10 (95% confidence interval [CI], 0.98-1.20); the risk seemed of only slightly greater magnitude for exposure to nonoxidative agents (1.18; 95% CI, 1.03-1.36) than to oxidative benzodiazepines (1.08; 95% CI, 0.95-1.23). Among the latter, the effect was mainly accounted for by the use of agents with a long elimination half-life. A dose relationship was observed exclusively among users of long half-life oxidative benzodiazepines. The risk associated with the use of nonoxidative benzodiazepines showed no relationship to the age of the patients. In contrast, patients aged 85 years or older receiving oxidative benzodiazepines at high dosages or as needed had a two- to three-fold increased risk of femur fracture than did patients in the younger age group. Among older individuals, the use of benzodiazepines slightly increased the risk of femur fracture, mainly irrespective of the metabolic fate of the drug. Our results suggest that the use of nonoxidative benzodiazepines does not carry a lower risk for femur fracture than does the use of oxidative benzodiazepines. However, the latter agents may be associated with a somewhat higher risk of side effects among the oldest old, especially at higher dosages.
使用苯二氮䓬类药物是老年人跌倒及由此导致股骨骨折的一个已明确的风险因素。不需要肝脏生物转化的苯二氮䓬类药物可能比经氧化代谢的药物更安全，因为氧化活性已显示会随年龄下降。本研究探讨了使用氧化型或非氧化型苯二氮䓬类药物与养老院老年人股骨骨折风险之间的关联。利用老年药物使用流行病学系统评估（SAGE）数据库进行了一项巢式病例对照研究；提取了1992年至1996年期间因首次发生股骨骨折而住院的9752例患者的记录，并按年龄、性别、州和索引日期与38564例对照患者的记录进行匹配。采用条件逻辑回归模型来估计股骨骨折的比值比（OR），并对潜在混杂因素进行调整。苯二氮䓬类药物总体使用的调整后OR为1.10（95%置信区间[CI]，0.98 - 1.20）；暴露于非氧化型药物（1.18；95% CI，1.03 - 1.36）的风险似乎仅略高于氧化型苯二氮䓬类药物（1.08；95% CI，0.95 - 1.23）。在后者中，这种影响主要由使用消除半衰期长的药物所致。仅在使用长半衰期氧化型苯二氮䓬类药物的人群中观察到剂量关系。使用非氧化型苯二氮䓬类药物相关的风险与患者年龄无关。相比之下，85岁及以上高剂量或按需使用氧化型苯二氮䓬类药物的患者股骨骨折风险比年轻年龄组患者增加了两到三倍。在老年人中，使用苯二氮䓬类药物会略微增加股骨骨折风险，主要与药物的代谢转归无关。我们的结果表明，使用非氧化型苯二氮䓬类药物导致股骨骨折的风险并不低于使用氧化型苯二氮䓬类药物。然而，在高龄老人中，尤其是高剂量使用时，后者可能会伴有略高的副作用风险。
