Genetic and environmental influences on bone mineral density in pre- and post-menopausal women

Genetic factors influencing acquisition of peak bone mass account for a substantial proportion of the variation in bone mineral density (BMD), although the extent to which genes also contribute to variation in bone loss is debatable. Few prospective studies of related individuals have been carried out to address this issue. To gain insights into the nature of the genetic factors contributing to variation in BMD, we studied 570 women from large Amish families. We evaluated and compared the genetic contributions to BMD in pre- and post-menopausal women, with the rationale that genetic variation in pre-menopausal women is due primarily to genetic determinants of peak bone mass, while genetic variation in post-menopausal women is due to the combined genetic effects of peak bone mass and bone loss. Bone mineral density was measured at one point in time at the hip and spine by dual energy X-ray absorptiometry (DXA). We used variance decomposition procedures to partition variation in BMD into genetic and environmental effects common to both groups and to pre- and post-menopausal women separately. Total variation in BMD was higher in post- compared to pre-menopausal women. Genes accounted for 58–88% of the total variation in BMD in pre-menopausal women compared to 37–54% of the total variation in post-menopausal women. In absolute terms, however, the genetic variance was approximately similar between the two groups because the environmental variance was 3 1/2- to 4-fold larger in the post-menopausal group. The genetic correlation in total hip BMD was 0.81 between pre- and post-menopausal women and differed significantly from one, consistent with the presence of at least some non-overlapping genetic effects in the two groups for BMD at this site. Overall, these analyses suggest that many, but not all, of the genetic factors influencing variation in BMD are common to both pre- and post-menopausal women.     

Duration of television viewing and bone mineral density in Chinese women

Studies on the relationship between television (TV) viewing and bone mineral density (BMD) in adults are limited. The purpose of this study was to examine whether longer duration of TV viewing increased the risk of lower BMD in Chinese women. A total of 626 female adults were voluntarily recruited into the study. Anthropometric measurements were obtained using standard procedures. Body composition including total body and regional BMD was estimated using dual-energy X-ray absorptiometry. The duration of TV viewing was categorized into 4 groups: <1 h, 1 to <2 h, 2 to <3 h, and ≥3 h. Multiple linear regression models were applied to analyze the associations between duration of TV viewing and total and regional BMD in all subjects and in subjects stratified by age of 45 years, respectively. After adjusting for age, BMI, alcohol use, smoking, education, income, urbanicity, leisure time physical activity, occupational physical activity, and menopause, the significant trend of pelvic BMD across categories of TV viewing was observed in all subjects (p < 0.05). Further analysis revealed that women aged <45 years, the 1 to <2 h group, the 2 to <3 h group, and the ≥3 h group were significantly associated with lower total body and regional BMD compared to women aged <45 years in the <1 h group. We concluded that the duration of TV viewing was negatively associated with BMD in Chinese women, especially in those aged 18–44 years. It might be sensible to reduce TV viewing time to prevent bone loss in young women.     

Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study

Osteoporosis is a major cause of disability in the United States. Numerous factors contribute to the decline in bone mineral density (BMD) that characterizes this disease, and the importance of heredity is now widely appreciated. We evaluated the joint contributions of genes and environmental factors on variation in BMD in 895 participants of the San Antonio Family Osteoporosis Study (SAFOS). Participants of the SAFOS ranged in age from 18 to 96 years and were members of 34 large families of Mexican American ancestry. BMD was measured at the spine, hip, and forearm by dual-energy X-ray absorptiometry. Information about medical history, lifestyle habits, dietary intake, and physical activity patterns was obtained by questionnaire. Age and body mass index were strongly associated with BMD at nearly every site; these and other measured risk factors accounted in aggregate for up to 46% of the total variation in BMD. In general, the environmental risk factors accounted for proportionately more of the total variation in BMD in men than in women. Genes accounted for 65-80% of the residual variation in spine and hip BMD, and 25-55% of the residual variability in forearm BMD. Although residual heritabilities were generally comparable between men and women across all ages combined, heritabilities at all sites tended to be higher in premenopausal women than in men younger than 50 years of age. Identifying the individual genes involved will shed insights into the processes that govern bone remodeling and may suggest strategies for the prevention of osteoporosis.     

Change in bone mineral density and its determinants in pre- and perimenopausal Chinese women: the Hong Kong perimenopausal women osteoporosis study

Summary  This 30-month study investigating bone change and its determinants in 438 perimenopausal Chinese women revealed that the fastest bone loss occurred in women undergoing menopausal transition but maintenance of body weight and physical fitness were beneficial for bone health. Soy protein intake also seemed to exert a protective effect. Introduction  This 30-month follow-up study aims to investigate change in bone mineral density and its determinants in Hong Kong Chinese perimenopausal women. Methods  Four hundred and thirty-eight women aged 45 to 55 years were recruited through random telephone dialing and primary care clinic. Bone mass, body composition, lifestyle measurements were obtained at baseline and at 9-, 18- and 30-month follow-ups. Univariate and stepwise multiple regression analyses were performed with the regression coefficients of BMD/C (derived from baseline and follow-up measurements) as the outcome variables. Menopausal status was classified as pre- or postmenopausal or transitional. Results  Menopausal status was the strongest determinant of bone changes. An annual bone loss of about 0.5% was observed among premenopausal, 2% to 2.5% among transitional, and about 1.5% in postmenopausal women. Multiple regression analyses, revealed that a positive regression slope of body weight was protective for follow-up bone loss at all sites. Number of pregnancy, soy protein intake and walking were protective for total body BMC. Higher baseline LM was also protective for neck of femur BMD. Conclusion  Maintenance of body weight and physical fitness were observed to have a protective effect on for bone loss in Chinese perimenopausal women.     

Genetic and environmental determinants of peak bone mass in young men and women.

Peak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER) a, and collagen type Ialpha1 (COLIA1) genes in relation to other factors such as birth weight, lifestyle diet, and exercise in a population-based cohort of 216 women and 244 men in their early 20s. Stepwise multiple regression analysis showed that body weight was the strongest predictor of bone mineral density (BMD) in women, accounting for 16.4% of the variance in spine BMD and 8.4% of the variance in femoral neck BMD. Other significant predictors were VDR genotype (3.8%) and carbohydrate intake (1.6%) at the spine and vitamin D intake (3.4%) and ER genotype (3.4%) at the femoral neck. Physical activity was the strongest predictor of BMD in men, accounting for 6.7% of the variance at the spine and 5.1% at the hip. Other significant predictors were body weight (5%) and ER PvuII genotype (2.8%) at the spine and weight (3.4%) and alcohol intake (2%) at the femoral neck. Birth weight was not a significant predictor of BMD at either site but COLIA1 genotype significantly predicted birth weight in women, accounting for 4.3% of the variance. We conclude that peak bone mass is regulated by an overlapping but distinct set of environmental and genetic influences that differ in men and women. However, much of the variance in BMD was unexplained by the variables studied here, which suggests that either most of the genes that regulate BMD remain to be discovered or major environmental influences on BMD exist that have not yet been identified.     

中日女性超声骨密度测定对比研究

目的 比较中日女性间的骨密度差异,探讨中国女性骨质疏松诊断标准。方法 采用定量超声衰减技术（BUA）测定114例健康女性,采取骨强度值与同类群日本女性相对比分析。结果 与同类群日本女性相比,中国女性骨密度值总体较低,但在统计学上无明显差异。结论 中国女性的骨质疏松诊断标准可参照日本女性标准建立。     

A referent bone mineral density database for Chinese American women

Introduction While osteoporosis is common among women of Chinese descent, a readily available bone mineral density (BMD) referent database for Chinese American women does not exist. Fracture risk among this population is currently assessed using a Caucasian reference as well as diagnostic criteria for osteoporosis developed for postmenopausal Caucasian women. Many studies indicate that there are important racial differences in skeletal health and fracture risk, an observation that makes the application of Caucasian data to all groups problematical. This study was undertaken to establish a BMD referent database in Chinese American women and to compare it with a Caucasian female database. It is expected that a race-specific database will be useful in the assessment of bone health for Chinese American women. Methods Healthy Chinese American women (n=359), ages 20–90, were recruited. Along with dual-energy X-ray absorptiometry (DXA) of the total hip and lumbar spine, demographic, medical, familial, nutritional, and behavioral data were obtained. The mean and standard deviation for BMD at each site was calculated for each 10-year age group and compared to mean BMD values for Caucasian women supplied as found in the Hologic DXA instrument. Osteoporosis diagnosis rates for this cohort, calculated with the Caucasian and newly established Chinese American BMD referent values, were compared with each other. Results Compared with Caucasian women, Chinese American women have significantly lower BMD at the lumbar spine, total hip, and femoral neck across a wide spectrum of age groups. As a consequence, more than one-half of Chinese American women ≥50 years of age, who would be characterized as osteoporotic using a Caucasian referent, would not be diagnosed as such if a Chinese American referent were utilized. Conclusion Chinese American reference BMD values are significantly lower than those for Caucasian women. Future studies relating Chinese American BMD values to fracture risk are necessary in order to determine if ethnic database-derived T-scores would be more predictive of fracture risk and to develop meaningful diagnostic criteria for this population.     

Estrogen receptor gene polymorphism and bone mineral density in postmenopausal Chinese women

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) for the estrogen receptor gene (ERG) and its relation to bone mineral density (BMD) were examined in 454 postmenopausal Chinese women, aged 55-79 years. The RFLPs were represented as P or p (PvuII) and X or x (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. There was no significant difference in BMD between the PP, Pp, and pp genotypes. However, women of the XX genotype had significantly higher BMD at the spine than women of the Xx or xx genotype. The magnitude of the difference in BMD was 80% of a standard deviation (SD) for BMD in elderly women and 40% of a SD in postmenopausal women. There was no statistically significant interaction between the PvuII genotype and the XbaI genotype in determining BMD. We conclude that postmenopausal Chinese women who were homozygous for the XX genotype had slightly higher BMD than the others. However, the difference in BMD was small and was unlikely to have any clinical significance. The ERG is not a major determinant of BMD in Chinese women in Hong Kong.     

Peak bone mineral density in Vietnamese women

Summary

This cross-sectional study showed that peak bone mineral density in Vietnamese women is comparable to that in Caucasian women; however, the prevalence of osteoporosis in post-menopausal Vietnamese women was slightly higher than in Caucasian women. The age of achieving peak bone mass in Vietnamese women was between 26 and 30 years.

Introduction

While peak bone mass and its determinants have been well-documented in Caucasian populations, little has been studied in Asian populations. The present study was designed to estimate the peak bone mineral density (BMD), age of its attainment, and to examine the prevalence of osteoporosis in Vietnamese women aged 50+.

Methods

The study was designed as a cross-sectional study with 328 women aged between 10 and 65 years (average age: 41) who were randomly selected from two districts around Hanoi city according to a stratified sampling scheme. BMD at the lumbar spine, femoral neck and total hip was measured by a DXA instrument (GE Lunar Prodigy, WI, USA). BMD was modeled as a cubic function of age, from which peak BMD and age at peak BMD were estimated. Bootstrap method was utilized to estimate the 95% confidence interval of peak BMD and age at peak BMD. From the peak BMD, T-score was calculated for each woman, and using the World Health Organization criteria, any woman with femoral neck BMD T-score ≤ -2.5 was classified as having osteoporosis.

Results

Peak BMD was estimated at 1.16 g/cm² (standard deviation [SD]: 0.13 g/cm²) at the lumbar spine, 1.02 g/cm² (SD 0.12) at the total hip, and 0.94 g/cm² (SD 0.11) at the femoral neck. In the cubic polynomial model, the age at peak BMD was estimated to range between 27 and 29 years. The prevalence of osteoporosis among those aged between 50 and 65 years was 23%. This prevalence was higher than in Chinese, Japanese, Korean and Caucasian populations.

Conclusion

These data suggest that although the peak BMD in Vietnamese women is comparable to, the prevalence of osteoporosis is higher than, in some other Asian and Caucasian women. It seems that osteoporosis is an important public health burden in Vietnam.     

Parity and bone mineral density in middle-aged women

A retrospective study was carried out to determine the relationship between parity and bone mineral density (BMD) in middle-aged women. Eight hundred and twenty-five woman aged 41–76 years were recruited from four general practice registers in Cambridge. Subjects were unselected as to their health status. Each subject completed a detailed health questionnaire. Participation rate was 50%. The main outcome measure was BMD measured at the spine (L2–4,n=825) and hip (neck, intertrochanter and Ward's triangle;n=817) by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR-1000 densitometer. It was found that the unadjusted mean BMD was significantly higher at all sites among the parous women (p=0.031 to <0.00001), and remained significantly higher at the femoral neck (p=0.025), intertrochanter (p=0.001) and Ward's triangle (p=0.045) after adjusting for age and body mass index (BMI). Similar findings were seen after stratifying for potential confounding variables. There was a consistent upward trend of BMD with increasing parity at all sites. Parity remained a significant independent predictor of BMD at all sites after controlling for age, BMI, menopausal status, oral contraceptive and hormone replacement therapy use, smoking status and breast-feeding status in multiple linear regression analyses. There was, on average, a 1.0% increase in BMD per live birth. Our findings therefore suggest a positive relationship between parity and bone mass.     

Body composition and bone mineral density of Chinese women with vertebral fracture

This study was designed to compare the body composition and bone mineral density measurements (BMD) in Chinese women with vertebral fracture and normal controls. A total of 400 community dwelling Chinese women aged 70–79 years old were studied. Vertebral height ratios were calculated from lateral thoracic and lumbar spine X-rays and subjects were classified into definite cases (n = 122), doubtful cases (n = 138) and normal controls (n = 140). Bone mineral density and body composition measurements were made by dual X-ray densitometry. The height, fat mass, lean mass, and BMD at all sites were significantly lower in patients with definite fracture than normal controls. Nevertheless, BMD at the hip was more predictive of vertebral fracture than BMD at the spine, the odds ratio in the lowest quartile of hip BMD being 3.8 (95% C.I. = 1.3 to 10.9). Finally, the extent of spinal deformity was poorly predicted by a combination of the anthropometric and BMD measurements, as only 12% of the total variance in TD1 was accounted for.     

中国围绝经期妇女体脂含量与骨密度关系的初步研究

目的探讨肌肉、脂肪含量与围绝经期骨质疏松妇女骨密度之间的关系。方法利用双能X线骨密度测量仪(美国,Hologic DiscoveryA型)测量门诊围绝经期妇女(90例,年龄:45~52岁(47.3±8.2))骨密度与体脂含量;同时测量登记受试者的年龄、身高、体重。结果结果显示,21%受试者腰椎和股骨骨量降低,全身脂肪含量(20675.129±5080.44)g与腰椎骨密度(0.91±0.177)g/cm2(P>0.05,r=-0.17)和髋部骨密度(0.99±0.102)g/cm2(P>0.05,r=0.158)没有相关性,肌肉含量(39790.80±6551.54)g与腰椎骨密度没有相关性(P>0.05,r=0.078),但是与髋部骨密度高度正相关(P<0.05,r=0.216)。体重(63.01±9.39)kg和腰椎(P<0.05,r=0.217)和髋部(P<0.05,r=0.305)骨密度高度正相关;BMI指数(24.6751±3.45637)与腰椎(P<0.05,r=0.244)和髋部(P<0.01,r=0.339)骨密度高度正相关。结论研究结果表明BMI指数和肌肉含量与围绝经期妇女髋部骨密度高度相关。     

Applying ethnic-specific bone mineral density T-scores to Chinese women in the USA

Summary

Caucasian reference data are used to classify bone mineral density in US women of all races. However, use of Chinese American reference data yields lower osteoporosis prevalence in Chinese women. The reduction in osteoporosis labeling may be relevant for younger Chinese women at low fracture risk.

Introduction

Caucasian reference data are used for osteoporosis classification in US postmenopausal women regardless of race, including Asians who tend to have lower bone mineral density (BMD) than women of white race. This study examines BMD classification by ethnic T-scores for Chinese women.

Methods

Using BMD data in a Northern California healthcare population, Chinese women aged 50–79 years were compared to age-matched white women (1:5 ratio), with femoral neck (FN), total hip (TH), and lumbar spine (LS) T-scores calculated using Caucasian versus Chinese American reference data.

Results

Comparing 4039 Chinese and 20,195 white women (44.8 % age 50–59 years, 37.5 % age 60–69 years, 17.7 % age 70–79 years), Chinese women had lower BMD T-scores at the FN, TH, and LS (median T-score 0.29–0.72 units lower across age groups, p?<?0.001) using Caucasian reference data. Using Chinese American BMD reference data resulted in an average +0.47, +0.36, and +0.48 units higher FN, TH, and LS T-scores, respectively, reducing the prevalence of osteoporosis (T-score?≤??2.5) in Chinese women at the FN (16.7 to 6.6 %), TH (9.8 to 3.2 %), and LS (23.2 to 8.9 %); osteoporosis prevalence at any one of three sites fell from 29.6 to 12.6 % (22.4 to 8.1 % for age 50–64 years and 43.2 to 21.0 % for age 65–79 years).

Conclusion

Use of Chinese American BMD reference data yields higher (ethnic) T-scores by 0.4–0.5 units, with a large proportion of Chinese women reclassified from osteoporosis to osteopenia. The reduction in osteoporosis labeling with ethnic T-scores may be relevant for younger Chinese women at low fracture risk.

     

Determinants of bone mineral density in Chinese-American women

Summary Few data are available regarding bone mineral density (BMD) and its determinants among Chinese Americans. We identified determinants of BMD among 359 Chinese-American women in order to identify risk factors for low BMD in this burgeoning population. BMD in Chinese-American women is influenced by a number of factors, including immigration. Introduction Osteoporosis and low BMD are common among Chinese women, including Chinese Americans, who are a growing population at risk for osteoporosis in the US. Few data are available regarding BMD and its determinants among Chinese-American women. Methods In this study, we examined predictors of BMD in 359 ambulatory Chinese-American women, ages 20–90, using stepwise multiple regression analysis. Variables in the model included age, weight, height, menarche age, years since menopause, immigration age, years in US, percentage of life in US, number of pregnancies, oral contraceptive use, family history of osteoporosis, family history of hip fracture, daily calcium intake, exercise, time outdoors, alcohol consumption and tobacco use. Results Among premenopausal women, weight was the strongest predictor of BMD, accounting for 10.5% of the variance at the lumbar spine (LS), 15.2% at the total hip (TH) and 16.6% at the femoral neck (FN). Time outdoors was also a positive predictor of BMD (1.4% at LS, 2.8% at TH and 1.6% at FN), while family history of osteoporosis (1.4% at TH) and age (3.7% at FN) were negative predictors. Among postmenopausal women, greater BMD at the LS and TH was associated with greater weight and earlier immigration age. Weight accounted for 16.4% of the variance at the LS and 19.8% at the TH; immigration age accounted for 3.1% of the variance at the LS and 4.1% at the TH. At the FN, years since menopause and weight were predictors of BMD, accounting for 14.4% and 8.7% of the variance, respectively. While older age at immigration had a negative effect on BMD, years in and proportion of life in the United States were not significant predictors of BMD. Conclusions Bone mineral density in Chinese-American women is influenced by a number of biological and lifestyle factors, including immigration. The results of this study provide new insights into risk factors for low bone density as they relate to environmental determinants in the growing population of Chinese-American women.     

围绝经期女性骨密度特点分析

目的总结并分析围绝经期女性腰椎1-4、股骨颈及髋关节部位的骨密度(bone mineral density,BMD)及其临床特点。方法收集2017年12月至2018年6月在我院住院部住院并进行双能X线吸收法骨密度检测的183例围绝经期女性,分别测定其腰椎1-4总体BMD、左侧股骨颈及左髋关节全部BMD,同时分析比较年龄、体质量指数(body mass index,BMI)与骨质疏松的关系。结果 183例患者中,检出骨质疏松39例(21. 3%),其中腰椎1-4、左股骨颈和左髋关节BMD各检出骨质疏松33例(18. 0%)、20例(10. 9%)、13例(7. 1%)。腰椎总体骨质情况与股骨颈、髋关节检查结果相符的各有129例(70. 5%)、119例(65. 0%),股骨颈总体骨质情况与髋关节检查结果相符的有137例(74. 9%)。在骨质疏松组、骨量减少组和骨量正常组,同一组病人腰椎1-4骨密度左髋关节骨密度左侧股骨颈骨密度,组间差异均有统计学意义。年龄、BMI与骨质疏松的发生均相关。骨质疏松与年龄呈正相关,与BMI、腰椎1-4总BMD、左股骨颈BMD、左髋关节BMD负相关,腰椎1-4 BMD与骨质疏松相关程度最高。结论腰椎整体骨密度呈现虚假升高趋势,腰椎1-4 BMD诊断骨质疏松的敏感性和特异性分别为84. 6%、100%,股骨颈分别为51. 3%、100%,髋关节分别为33. 3%、100%;年龄增长、BMI偏低会增加围绝经期妇女罹患骨质疏松的风险。     

Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density

Summary One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD. Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women. Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year. Results A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (±0.018), +0.58%, while it decreased −0.003 g/cm2 (±0.019), −0.36%, (p = 0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site. Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.     

High bone mineral density among perimenopausal women

Studies regarding high bone mineral density (HBMD) are few. In the population-based Kuopio Osteoporosis Risk Factor and Prevention Study, BMDs of women were measured from 1990–1991 and 1995–1997. The mean age of the 1,873 women studied was 53.5 years at baseline (range 48.0–59.6). In all, 248 women were excluded because of BMD measurement errors or artifacts: 41 from the HBMD group (20.6%) and 207 (12.4%) from the control group. The final study group consisted of 1,551 women, 168 in the HBMD group (baseline lumbar BMD >1.23 g/cm²; femoral BMD >1.01 g/cm², and 5-year follow-up lumbar BMD >1.21 g/cm²; femoral BMD >0.98 g/cm², respectively) and 1,383 in the control group. The predictors for HBMD in the multivariate regression analysis were as follows: hormone therapy (HT) during the follow-up from 0.5 to 2 years and for over 2 years (OR 2.06, CI: 1.11–3.81 and OR 2.16, CI 1.43–3.26) and being overweight (BMI from 25 kg/m² to 30 kg/m², and BMI >30 kg/m²) at baseline (OR 2.84, CI: 1.82–4.42; OR 5.94, CI: 3.47–10.16, respectively). High physical activity while 11–18 years of age was associated with HBMD (OR 1.69, CI: 1.17–2.45). Parity predicted HBMD so that after one to two births the OR was 2.66 (CI: 1.03–6.88) and 3.03 (CI: 1.16–7.90) after three or more births. Menopause was negatively associated with HBMD (OR 0.57, CI 0.38–0.85). There were more premenopausal women in the HBMD group (53.9 vs. 34.6%, P <0.001). The HBMD group showed fewer fractures. In conclusion, being overweight, parity, HT use, premenopause and high physical activity in adolescence seemed to be predictors for persistently high BMD in early postmenopausal women. We suggest that the fracture risk is low in these women, and thus they are neither primary candidates for BMD screening nor for osteoporosis medication.