补充维生素D预防骨折——随机对照试验汇总分析

背景：对于脊椎以外的骨折而言，补充口服维生素D的预防作用和用量仍无定论。 目的：评估补充维生素D在预防老年髋骨骨折和非脊椎骨折方面的效果。 数据来源：使用MEDLINE、Cochrance对照试验记录（1960～2005年）以及EMBASE（1991-2005年），对英文和非英文文章进行系统回顾。通过与临床专家接触，通过检索美国社会骨和骨矿研究协会提供的参考文献和摘要（1995～2004年）．进一步寻找更多的研究。检索词包括随机对照试验（randomized controlled trial，RCT）、临床对照试验、随机分配、双盲法、维生素D3、维生素D2；25-羟基维生素D、骨折、人类、老年、摔倒和骨密度。 研究选取：纳入的研究仅限于口服补充维生素D（维生素D3、维生素D2、补钙或不补钙）与补钙或安慰剂比较的双盲RCTs。试验于检查髋部骨折或非脊椎骨折的老年人（年龄≥60岁）中进行。数据提取：两位作者根据预先规定独立提取相关数据，其中包括研究质量指标。 数据综合：所有的汇总分析均以随机效应模型为基础。5项有关髋部骨折的RCTs（n=9294）和7项有关非脊椎骨折危险的RCTs（n=9820）符合我们的纳入标准。所有试验均使用了维生素D3。对髋部和非脊椎骨折预防研究的异质性亦进行观察，用低剂量（400IU／d）和高剂量（700～800IU／d）分别合并RCTs后异质性消失。与补钙或安慰剂相比，每天服700～800IU的维生素D可使髋部骨折的相对危险（relative risk，aa）下降26％（3项RCTs共计5572人；RR，0．74；95％可信区间[confidence interval，CI]，0．61～0．88），使非脊椎骨折的相对危险下降23％（5项RCTs共计6098人；RR，0．77；95％CI，0．68～0．87）。每天服400IU的维生素D（2项RCTs共计3722人；髋部骨折RR，1．15；95％CI，0．88～1．50；非脊椎骨折RR，1．03；95％CI，0．86—1．24）未见明显获益。 结论：口服补充维生素D（700～800IU／d）可以降低尚能活动的老人或慈善机构收容的老年人发生髋部骨折和脊椎以外骨折的危险，每天口服400IU维生素D并不足以预防骨折。     

Adiposity and sex hormones in girls.

Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone-binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 microg/dL compared with 78.8 microg/dL for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P(trend) = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P(trend) < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research.     

Prospective study of relative weight, height, and risk of breast cancer

We examined relative weight and height in relation to subsequent breast cancer risk among 115,534 women 30 to 55 years of age and free from cancer in 1976. By 1984, six hundred fifty-eight premenopausal and 420 postmenopausal breast cancers were documented during 734,716 person-years. Among premenopausal women, risk of breast cancer decreased significantly with increasing relative weight (relative risk for the highest category was 0.6). A similar inverse association was seen for recalled relative weight at 18 years of age. Postmenopausal breast cancer was not associated with relative weight, either recent or at age 18. Height was not associated with breast cancer risk among premenopausal women and only weakly related among postmenopausal women. These data suggest that obesity among premenopausal and early postmenopausal women does not increase breast cancer risk substantially.     

Reproducibility and validity of self-reported menopausal status in a prospective cohort study

The reproducibility and validity of self-reported menopausal status were evaluated among the 121,700 female US registered nurses aged 30-55 years in 1976 who are participants in the Nurses' Health Study, a prospective cohort study of diseases in women. When questioned in 1978, 6,591 of the women who were premenopausal in 1976 reported that their menses had ceased and provided their age at menopause. Two years later, in 1980, 98.8 per cent of the 6,591 women again reported that they were postmenopausal and again gave the reasons for menopause (natural or surgical). Among those women who reported surgical menopause during the 1976-1978 follow-up interval, age at menopause was reported to within one year on both the 1978 and 1980 questionnaires by 95 per cent of women. Among those reporting natural menopause during the 1976-1978 period, 82 per cent of women reported their age at menopause to within one year on the two follow-up questionnaires. A random sample of 255 women reporting surgical menopause between 1982 and 1984 was identified and medical records were obtained for 200. For all but two women, there was complete agreement between self-report and medical record for details of hysterectomy and extent of ovarian surgery. The reproducibility of self-reported age at menopause was assessed among 31,405 women who were menopausal in 1976. Reported age at menopause on consecutive questionnaires showed increasing within-person variance with increasing duration since menopause.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk of symptomatic gallstones in women with severe obesity.

Although obesity is a well-recognized risk factor for gallstones, the excess risks associated with higher levels of obesity and recent weight change are poorly quantified. We evaluated these issues in the Nurses' Health Study. Among 90,302 women aged 34-59 y at baseline followed from 1980 to 1988, 2122 cases of newly diagnosed symptomatic gallstones occurred during 607,104 person-years of follow-up. From 1980 to 1986, 488 cases of newly diagnosed unremoved gallstones were documented. We observed a striking monotonic increase in gallstone disease risk with obesity; women with a body mass index (BMI) greater than 45 kg/m2 had a sevenfold excess risk compared with those whose BMI was less than 24 kg/m2. Women with a BMI greater than 30 kg/m2 had a yearly gallstone incidence of greater than 1% and those with a BMI greater than or equal to 45 kg/m2 had a rate of approximately 2%/y. Recent weight loss was associated with a modestly increased risk after adjustment for BMI before weight loss. Current smoking was an independent risk factor; women smoking greater than or equal to 35 cigarettes/d had a relative risk of 1.5 (95% CI 1.2-1.9).     

Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women

We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years since last [corrected] use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk.