同型半胱氨酸水平与骨质疏松性骨折风险

Homocysteine levels and the risk of osteoporotic fracture.

作者信息

van Meurs Joyce B J, Dhonukshe-Rutten Rosalie A M, Pluijm Saskia M F, van der Klift Marjolein, de Jonge Robert, Lindemans Jan, de Groot Lisette C P G M, Hofman Albert, Witteman Jacqueline C M, van Leeuwen Johannes P T M, Breteler Monique M B, Lips Paul, Pols Huibert A P, Uitterlinden André G

机构信息

Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

出版信息

N Engl J Med. 2004 May 13;350(20):2033-41. doi: 10.1056/NEJMoa032546.

DOI:10.1056/NEJMoa032546

PMID:15141041

Abstract

BACKGROUND

Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures.

METHODS

We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture, with adjustment for age, sex, body-mass index, and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels.

RESULTS

During 11,253 person-years of follow-up, osteoporotic fractures occurred in 191 subjects. The overall multivariable-adjusted relative risk of fracture was 1.4 (95 percent confidence interval, 1.2 to 1.6) for each increase of 1 SD in the natural-log-transformed homocysteine level. The risk was similar in all three cohorts studied, and it was also similar in men and women. A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture (95 percent confidence interval, 1.4 to 2.6). The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture.

CONCLUSIONS

An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.

摘要

背景

血浆同型半胱氨酸水平极高是同型胱氨酸尿症的特征，这是一种罕见的常染色体隐性疾病，伴有全身性骨质疏松症的早期发作。因此，我们推测轻度升高的同型半胱氨酸水平可能与年龄相关的骨质疏松性骨折有关。

方法

我们研究了2406名年龄在55岁及以上的受试者循环同型半胱氨酸水平与骨质疏松性骨折发生风险之间的关联，这些受试者参与了两项独立的前瞻性、基于人群的研究。在鹿特丹研究中，有两个独立队列：队列1中有562名受试者，平均随访期为8.1年；队列2中有553名受试者，平均随访期为5.7年。在阿姆斯特丹纵向衰老研究中，有一个由1291名受试者组成的单一队列，平均随访期为2.7年。采用多变量Cox比例风险回归模型分析骨折风险，并对年龄、性别、体重指数以及其他可能与骨折风险或同型半胱氨酸水平升高相关的特征进行调整。

结果

在11253人年的随访期间，191名受试者发生了骨质疏松性骨折。自然对数转换后的同型半胱氨酸水平每增加1个标准差，骨折的总体多变量调整相对风险为1.4（95%置信区间，1.2至1.6）。在所有三项研究队列中风险相似，在男性和女性中也相似。同型半胱氨酸水平处于最高年龄特异性四分位数与骨折风险增加1.9倍相关（95%置信区间，1.4至2.6）。同型半胱氨酸水平与骨折风险之间的关联似乎独立于骨矿物质密度和其他潜在的骨折风险因素。