Kinjo Mitsuyo, Setoguchi Soko, Schneeweiss Sebastian, Solomon Daniel H
Department of Internal Medicine, Teine Keijinkai Hospital, Sapporo, Japan.
Am J Med. 2005 Dec;118(12):1414. doi: 10.1016/j.amjmed.2005.07.033.
Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample.
We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index.
In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs--benzodiazepines or antidepressants--were not associated with significantly reduced bone mineral density.
In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.
根据世界卫生组织的定义，骨矿物质密度降低可诊断为骨质疏松症，且是未来骨折的重要预测指标。使用多种类型的中枢神经系统活性药物，包括苯二氮䓬类药物、抗惊厥药、抗抑郁药和阿片类药物，均与骨折风险增加有关。然而，尚不清楚这种风险增加是与骨矿物质密度的影响有关，还是与其他因素有关，如跌倒风险增加。我们试图在美国一个具有代表性的基于人群的样本中研究骨矿物质密度与苯二氮䓬类药物、抗惊厥药、抗抑郁药和阿片类药物使用之间的关系。
我们分析了第三次全国健康与营养检查调查（NHANES III，1988 - 1994年）中17岁及以上成年人的数据。通过双能X线吸收法测量了7114名男性和7532名女性参与者的总股骨骨矿物质密度。使用多变量线性回归模型来量化中枢神经系统药物暴露与总股骨骨矿物质密度之间的关系。模型对包括年龄、性别和体重指数在内的相关协变量进行了控制。
在多变量线性回归模型中，在调整了几个潜在混杂因素后，与未使用者（0.95 g/cm²；95%置信区间[CI]：0.95至0.95）相比，服用抗惊厥药（0.92 g/cm²；95% CI：0.89至0.94）和阿片类药物（0.92 g/cm²；95% CI：0.88至0.95）的受试者骨矿物质密度显著降低。其他中枢神经系统活性药物——苯二氮䓬类药物或抗抑郁药——与骨矿物质密度显著降低无关。
在对NHANES III的横断面分析中，抗惊厥药和阿片类药物（而非苯二氮䓬类药物或抗抑郁药）与骨矿物质密度显著降低有关。这些发现对骨折预防策略具有启示意义。
