Michaëlsson Karl, Lithell Hans, Vessby Bengt, Melhus Håkan
Department of Surgical Sciences, Section of Orthopedics, University Hospital, Uppsala, Sweden.
N Engl J Med. 2003 Jan 23;348(4):287-94. doi: 10.1056/NEJMoa021171.
Although studies in animals and epidemiologic studies have indicated that a high vitamin A intake is associated with increased bone fragility, no biologic marker of vitamin A status has thus far been used to assess the risk of fractures in humans.
We enrolled 2322 men, 49 to 51 years of age, in a population-based, longitudinal cohort study. Serum retinol and beta carotene were analyzed in samples obtained at enrollment. Fractures were documented in 266 men during 30 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to the serum retinol level.
The risk of fracture was highest among men with the highest levels of serum retinol. Multivariate analysis of the risk of fracture in the highest quintile for serum retinol (>75.62 microg per deciliter [2.64 micromol per liter]) as compared with the middle quintile (62.16 to 67.60 microg per deciliter [2.17 to 2.36 micromol per liter]) showed that the rate ratio was 1.64 (95 percent confidence interval, 1.12 to 2.41) for any fracture and 2.47 (95 percent confidence interval, 1.15 to 5.28) for hip fracture. The risk of fracture was further increased within the highest quintile for serum retinol. Men with retinol levels in the 99th percentile (>103.12 microg per deciliter [3.60 micromol per liter]) had an overall risk of fracture that exceeded the risk among men with lower levels by a factor of seven (P<0.001). The level of serum beta carotene was not associated with the risk of fracture.
Our findings, which are consistent with the results of studies in animals, as well as in vitro and epidemiologic dietary studies, suggest that current levels of vitamin A supplementation and food fortification in many Western countries may need to be reassessed.
尽管动物研究和流行病学研究表明，高维生素A摄入量与骨脆性增加有关，但迄今为止，尚未使用维生素A状态的生物标志物来评估人类骨折风险。
我们纳入了2322名年龄在49至51岁之间的男性，进行一项基于人群的纵向队列研究。在入组时采集的样本中分析血清视黄醇和β-胡萝卜素。在30年的随访期间，记录了266名男性的骨折情况。采用Cox回归分析根据血清视黄醇水平确定骨折风险。
血清视黄醇水平最高的男性骨折风险最高。与血清视黄醇水平处于中间五分位数（62.16至67.60微克/分升[2.17至2.36微摩尔/升]）的男性相比，对血清视黄醇水平处于最高五分位数（>75.62微克/分升[2.64微摩尔/升]）的男性骨折风险进行多变量分析显示，任何骨折的发生率比值为1.64（95%置信区间为1.12至2.41），髋部骨折的发生率比值为2.47（95%置信区间为1.15至5.28）。在血清视黄醇水平最高的五分位数内，骨折风险进一步增加。视黄醇水平处于第99百分位数（>103.12微克/分升[3.60微摩尔/升]）的男性总体骨折风险比水平较低的男性高出7倍（P<0.001）。血清β-胡萝卜素水平与骨折风险无关。
我们的研究结果与动物研究以及体外和流行病学饮食研究的结果一致，表明许多西方国家目前的维生素A补充和食品强化水平可能需要重新评估。
