Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study

Summary  Peak bone mass is an important determinant of bone mass in later life, but the age of peak bone mass is still unclear. We found that bone size and density increase and bone turnover decreases until age 25. It may be possible to influence bone accrual into the third decade. Introduction  Peak bone mass is a major determinant of bone mass in later life. Bone growth and maturation is site-specific, and the age of peak bone mass is still unclear. It is important to know the age to which bone accrual continues so strategies to maximise bone mass can be targeted appropriately. This study aims to ascertain the age of lumbar spine peak bone mass. Methods  We measured lumbar spine BMC, estimated volume and BMAD by DXA and biochemical markers of bone turnover in 116 healthy males and females ages 11 to 40, followed up at an interval of five to nine years. Results  The majority of peak bone mass was attained by the mid-twenties. Increases in BMC in adolescents and young adults were mostly due to increases in bone size. Bone turnover markers decreased through adolescence and the third decade and the decreasing rate of change in bone turnover corresponded with the decreasing rate of change in lumbar spine measurements. Conclusions  Skeletal maturation and bone mineral accrual at the lumbar spine continues into the third decade.     

新疆维吾尔族人群雄激素受体基因CAG重复多态性与良性前列腺增生的关系

目的　初步探讨雄激素受体 (AR)基因CAG重复多态性与良性前列腺增生 (BPH)的关系。　方法　收集 80例维吾尔族BPH患者和 4 0例健康者外周血标本 ,应用PCR和直接测序法行AR基因CAG重复长度测定。分析评价CAG重复长度与BPH的关系。　结果　BPH组CAG重复次数范围 13～ 30 ,平均 2 2 .78。对照组CAG重复次数范围 14～ 2 9,平均 2 2 .38。两组比较差异无显著性意义 (P >0 .0 5 )。CAG重复长度 <2 2和≥ 2 2比较 ,其OR值为 1.0 6 (95 %CI 0 .4 6～ 2 .4 8,P >0 .0 5 )。CAG重复长度与BPH患者年龄 (γ =- 0 .0 6 ,P >0 .0 5 )、国际前列腺症状评分 (IPSS) (γ =0 .11,P >0 .0 5 )无相关性 ,而与前列腺的体积相关 (γ =- 0 .2 6 ,P <0 .0 5 )。在BPH患者 ,前列腺体积随着CAG重复次数的增加而减小 ,差异有显著性意义 (趋势检验P <0 .0 5 ) ,CAG重复长度≤ 2 0与≥ 2 5相比 ,前列腺体积差异有显著性意义 (P =0 .0 5 )。　结论　AR基因CAG重复长度与BPH腺体的增长有关。     

Association of estrogen receptor α gene polymorphisms with bone mineral density in Chinese women: a meta-analysis

Introduction and hypothesis A large number studies have examined the association between estrogen receptor alpha (ESR-α) gene polymorphisms and bone mineral density (BMD) in the Chinese population. We conducted a meta-analysis to assess their pooled effects. Methods We searched for all published articles indexed in MEDLINE, the Chinese Biomedical Database, and the Chinese Journal Full-text Database from January 1994 to April 2006. Any cross-sectional study that tested the association between ESR-α PvuII or XbaI genotypes and BMD at the femoral neck or spine in Chinese women was included in the review. Data were extracted independently by two reviewers using a standardized data extraction form. Sixteen eligible studies involving 4,297 Chinese women were identified. Results The overall frequencies of X and P alleles were 28% and 40%, respectively. The PvuII polymorphism was statistically significantly associated with BMD at the femoral neck (P = 0.038 for PP = Pp = pp) but not at the lumbar spine in all women. The BMD difference for the contrasts of PP versus Pp/pp genotypes was −0.0105 (95%CI, −0.0202 ∼ −0.0008) g/cm² (P = 0.036). The XbaI polymorphism was not associated with BMD at the femoral neck or lumbar spine. Conclusion The PvuII polymorphism had a very weak association with femoral neck BMD whereas XbaI polymorphism was unlikely to be a predictor of femoral neck or spine BMD in Chinese women.     

广西南宁地区汉壮族人群骨密度及骨质疏松患病率研究

目的 评估广西南宁地区汉壮族健康人群骨量和骨质疏松(OP)的发病情况。方法 l084名健康人群采用双能x线骨密度仪检测腰椎正位、髋部、前臂的骨密度(BMD)值。按民族、年龄、性别进行分组，以10岁作为1个年龄段。结果 骨峰值年龄分布：男女汉壮族各部位骨峰值年龄在30-39岁，60岁后OP患病率(WHO)汉族男性23．36％，壮族男性25．00％，汉族女性31．69％，壮族女性44．44％，汉壮族男女各年龄段和总体OP患病率差异无显性。结论 广西南宁地区汉壮族男女健康人群峰值骨密度水平及骨质疏松检出率差异无显性。     

Prevalent fractures are related to cortical bone geometry in young healthy men at age of peak bone mass

Low areal bone mass is a risk factor for fractures in men. Limited data are available on fractures and bone geometry in men, and the relation with sex steroids is incompletely understood. We investigated prevalent fractures in relation to peak bone mass, bone geometry, and sex steroids in healthy young men. Healthy male siblings (n = 677) at the age of peak bone mass (25 to 45 years) were recruited in a cross‐sectional population‐based study. Trabecular and cortical bone parameters of the radius and cortical bone parameters of the tibia were assessed using peripheral quantitative computed tomography (pQCT). Areal bone mineral density (aBMD) was determined using dual‐energy X‐ray absorptiometry (DXA). Sex steroids were determined using immunoassays, and fracture prevalence was assessed using questionnaires. Fractures in young men were associated with a longer limb length, shorter trunk, lower trabecular BMD, smaller cortical bone area, and smaller cortical thickness (p < .005) but not with bone‐size‐adjusted volumetic BMD (vBMD). With decreasing cortical thickness [odds ratio (OR) 1.4/SD, p ≤ .001] and decreasing cortical area (OR 1.5/SD, p ≤ .001), fracture odds ratios increased. No association between sex steroid concentrations and prevalent fractures was observed. Childhood fractures (≤15 years) were associated with a thinner bone cortex (?5%, p ≤ .005) and smaller periosteal size (?3%, p ≤ .005). Fractures occurring later than 15 years of age were associated with a thinner bone cortex (?3%, p ≤ .05) and larger endosteal circumference (+3%, p ≤ .05) without differences in periosteal bone size. In conclusion, prevalent fractures in healthy young men are associated with unfavorable bone geometry and not with cortical vBMD when adjusting for bone size. Moreover, the data suggest different mechanisms of childhood fractures and fractures during adult life. © 2010 American Society for Bone and Mineral Research     

Longitudinal measurement of regional and whole body bone mass in young healthy adults

The so-called peak bone mass (PBM) represents the highest amount of bony tissue achieved during life at a given site of the skeleton. It has been suggested that PBM might be achieved as late as the fourth decade, but recent data have indicated that PBM is already achieved by the end of sexual maturation, namely at the end of the second decade. The solving of this apparent controversy is of interest for a better understanding of bone homeostasis and for defining the cohort of normal subjects to be evaluated in order to establish a PBM reference range — necessary for the diagnosis of osteoporosis and evaluation of the fracture risk. To study bone mass evolution in young healthy adults and to determine whether such a cohort can be used to establish PBM reference values, we measured bone mineral density (BMD) in sixty 20- to 35-year-old young healthy adults by dual-energy X-ray absorptiometry at the levels of the lumbar spine (in both anteroposterior and lateral views), femoral neck, trochanter region, total hip and of Ward's triangle, as well as whole-body BMD and bone mineral content (BMC) in cross-sectional and longitudinal studies. In the cross-sectional analysis, none of the bone mass variables was dependent on age using linear regression analysis. The longitudinal study indicated that the mean changes in lumbar spine, proximal femur and whole body BMD or BMC determined after a 1-year interval were not statistically different from zero in either females or males aged 20–35 years. In conclusion, the present results confirm that at the levels of lumbar spine and proximal femur, two sites particularly at risk of osteoporotic fractures, PBM can be achieved before the third and fourth decades in both male and female normal subjects.     

Vitamin D receptor gene polymorphism,bone mass,body size,and vitamin D receptor density

We determined vitamin D receptor (VDR) gene alleles (based on the BsmI restriction site polymorphism), duodenal mucosal receptor density, bone mass at spine and total body, and body size in 32 healthy premenopausal females. While we found no relationship between allele and receptor density in duodenal mucosa, bone mineral content (BMC) at both spine and total body was significantly associated with VDR gene alleles. BMC was highest for the bb allele, lowest for BB, and intermediate for Bb. A similar association was noted between allele and body size variables, particularly weight. When BMC was adjusted for body weight, the association with VDR polymorphism disappeared. The VDR gene polymorphism may be affecting bone mass not through classical nutritional mechanisms (e.g., intestinal calcium absorption), but through an influence on body size.     

Association between two types of vitamin d receptor gene polymorphism and bone status in premenopausal Japanese women

Polymorphisms in the vitamin D receptor (VDR) gene using ultrasound (US) bone mass and bone metabolic markers were investigated as potential genetic markers for osteoporosis in 126 premenopausal Japanese women aged 27.2 +/- 10.1 (mean +/- SD) years. The relationship between their VDR gene polymorphisms and bone states was determined. VDR genotypes were based on the absence (B) or presence (b) of the Bsm I restriction site (B polymorphism), and ATG (the M allele) and ACG (the m allele) sequences at the translation initiation site (M polymorphism). Genotype frequencies were 73.8%, bb; 24.6%, Bb; 1.6%, BB; 15.1%, MM; 51.6%, Mm and 33.3%, mm. The stiffness index of calcaneal bone minerals measured by an US bone densitometer was significantly higher in the mm types (P <0.05 versus MM) than in the Mm types (P <0.01 versus MM) and MM types. There was no significant difference between in B polymorphisms. Furthermore, bone mass was correlated with serum bone type alkaline phosphatase (ALP) activity and urinary deoxypyridinoline concentration in M polymorphisms. Because the distribution of B polymorphisms in each M polymorphism genotype did not differ, M polymorphisms were affected independently from B polymorphisms to bone mass or bone metabolic markers. No significant difference was observed in nutritional intake and food consumption among genotypes. In the MM and Mm types, the bone mass was closely related to the frequency of milk intake during the periods of elementary and junior high school. In contrast, bone mass was not associated with nutritional intake or the frequency of past milk intake in B polymorphisms. Therefore, the M polymorphism of the VDR gene is a stronger genetic indicator of osteoporosis than the B polymorphism in premenopausal Japanese woman.     

The polymorphic androgen receptor gene CAG repeat,pituitary-testicular function and andropausal symptoms in ageing men

The activity of androgen receptor (AR) is modulated by a polymorphic CAG trinucleotide repeat in the AR gene. In the present study, we investigated hormonal changes among ageing men, and whether the number of AR CAG triplets is related to the appearance of these changes, as well as symptoms and diseases associated with ageing. A total of 213 41-70-year-old men donated blood for hormone analyses (LH, testosterone, oestradiol and SHBG) and answered questions concerning diseases and symptoms associated with ageing and/or androgen deficiency. Of these men, 172 donated blood for the measurement of the CAG repeat length of AR. The CAG repeat region of the AR gene was amplified by polymerase chain reaction (PCR) and the products were sized on polyacrylamide gels. The repeat number was analysed as a dichotomized variable divided according to cut-off limits of the lowest (< or =20 repeats) and the highest quartile (> or =23 repeats), and as a continuous variable. The proportion of men with serum LH in the uppermost quartile (>6.0 IU/L) with normal serum testosterone (>9.8 nmol/L, above the lowest 10%) increased significantly with age (p = 0.01). There were fewer men with this hormonal condition among those with CAG repeat number in the uppermost quartile (> or =23 repeats) (p = 0.03). These men also reported less decreased potency (p < 0.05). The repeat number was positively correlated with depression, as expressed by the wish to be dead (r = 0.45; p < 0.0001), depressed mood (r = 0.23; p = 0.003), anxiety (r = 0.15; p < 0.05), deterioration of general well-being (r = 0.22; p = 0.004), as well as decreased beard growth (r = 0.49; p < 0.0001). A hormonal condition where serum testosterone is normal but LH increased is a frequent finding in male ageing. Only certain types of age-related changes in ageing men were associated with the length of the AR gene CAG repeat, suggesting that this parameter may play a role in setting different thresholds for the array of androgen actions in the male.     

老年男性维生素D受体基因多态性与骨密度关系的研究

目的研究维生素D受体(vitamin D receptor,VDR)基因多态性在老年男性中的分布, 并进一步研究其与骨密度的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR- RFLP)方法,分析145例老年男性的VDR基因型,同时用双能X线吸收法测定腰椎及髋部骨密度。结果 VDR基因型分别为BB,0．014;Bb,0．117;bb,0．869。骨质疏松组与非骨质疏松组之间VDR基因型分布频率的差异无显著性(P>0．05)。比较各基因型组的骨密度,bb组及 Bb组只有在股骨颈处显示出BMD均低于BB组,差异有显著性(P<0．05),其它部位,三个基因型组的BMD均差异无显著性(P>0．05)。结论老年男性VDR基因型分布频率与某些西方国家人群分布不同,其VDR基因型与骨密度无明显相关性。VDR基因可能不是我们所研究群体 BMD的主要遗传基因。     

Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls

We assessed the main and interaction effects of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. A total of 228 premenarche Chinese girls (9-11.5 years old) were recruited for a 2-year follow-up study. Bone mineral density (BMD) at the total body, lumbar spine (L1-L4), and total left hip were measured by dual-energy X-ray absorptiometry at baseline and follow-up. The -174G/C and -634C/G polymorphism of IL-6 gene, and PvuII and XbaI polymorphisms of the estrogen receptor (ER)-alpha gene, were determined. The -634C/G polymorphism of the IL-6 gene and PvuII polymorphism of ER-alpha gene were significantly associated with bone mass accrual after adjusting the potential confounding factors. Girls with pp genotype of ER-alpha gene had greater percentage accrual in BMD of total body (P = 0.010) and femoral intertrochanter (P = 0.038) than their PP and Pp counterparts. Girls with CC genotype of IL-6 -634G/C gene had higher percentage accrual in BMD of total body (P = 0.032) and femoral trochanter (P = 0.048) than their CG + GG counterparts. Significant interaction effects of IL-6 -634C/G polymorphism and ER-alpha PvuII polymorphism were observed on percentage change in BMD of total left hip (P = 0.009) and femoral intertrochanter (P = 0.007). The genotype CC (IL-6 -634C/G) x pp (ER-alpha PvuII) was associated with greater BMD accrual than other genotype combination in Chinese adolescent girls. We found that the IL-6 -634C/G and ER-alpha PvuII polymorphism were significantly associated with BMD accrual and that they have an interactional effect on BMD accrual in Chinese adolescent girls.     

Relation of height and weight to the regional variations in bone mass among Japanese-American men and women

We examined the magnitude of regional variations in bone mass among elderly, Japanese-American men and women. All subjects had bone measurements at the calcaneus, and at the distal and proximal radius sites. A subset of the women had, in addition, spine bone mass measurements. To provide a common measurement scale, the bone measurements were converted to age- and sex-specificZ-scores. TheZ-scores between pairs of bone sites were then subtracted to yield the differences in bone mass between bone sites (expressed inZ-score units). For most individuals the differences were less than 1.0Z-score; however, 12%–20% of the differences were at least 1Z-score apart. The most similar sites were the distal and proximal radius: different regions within the same bone. Among the other bone pairs, the calcaneus and spine were the most similar to one another. The magnitudes of the differences in bone mass were associated with height and weight. Heavier subjects, for instance, had greater calcaneus than radius bone mass measurements, and greater spine than radius measurements. The spine and calcaneus are more weight-bearing than the radius sites. Associations were observed up to 0.25Z-score per 10 kg difference in weight. Height was associated with bone mass differences in an opposite direction to weight. Taller subjects had greater bone mass at the radius sites than expected from their calcaneus or spine bone measurements (0.1 to 0.2Z-score difference per 5 cm difference in height). Bone width partly explained the associations with height; that is, adjusting the radius widths reduced the associations with height. Overall, our results indicate that small to moderate differences between bone sites were common among our study population, and that the magnitudes of the differences were associated with height and weight.     

Racial difference in the correlates of bone mineral content/density and age at peak among reproductive-aged women

Summary  Racial/ethnic differences were observed in age at peak bone density and their correlates, with whites peaking at least 5 years earlier at the femoral neck than black and Hispanic women. Race-specific standards generated in this study could be useful when interpreting bone densitometry data in young women. Introduction  The influence of race/ethnicity on bone measurements has not been widely examined. This study identifies age and amount of bone accumulated at peak density and their correlates by race/ethnicity. Methods  Bone mineral content (BMC) and bone mineral density (BMD) of the spine and femoral neck were measured by dual X-ray absorptiometry in 708 white, black, and Hispanic reproductive-aged women. Race-specific nonlinear models were used to describe the relationship between age and bone measurements, after adjusting for body weight and height. Log-transformed bone measurements were used to determine predictors based on multiple linear regression. Results  Predictors, which were race and site specific, included age, age at menarche, body weight, height, months of depot medroxyprogesterone acetate use, weight-bearing exercise, and alcohol use. Women of all races gained BMC and BMD at the spine up to 30–33 years of age. BMC and BMD of the femoral neck peaked among white women earlier (≤16 years) than among blacks (BMC 22 years; BMD 21 years) and Hispanics (BMC 29 years; BMD 20 years). Conclusion  Age at peak bone mass and its correlates differ by race/ethnicity. Race-specific standards generated in this study could be useful when interpreting bone densitometry data in young women. This work was supported by the National Institute of Child Health and Human Development grants R01HD39883 and K24HD043659 awarded to ABB and General Clinical Research Centers (GCRC) program, National Center for Research Resources, NIH, M01RR000073.     

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Summary The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1. Methods The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029). Conclusions ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.     

Association of vitamin D and estrogen receptor gene polymorphism with the effects of longterm hormone replacement therapy on bone mineral density

We longitudinally studied whether vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphisms in Japanese women influenced the effect of longterm hormone replacement therapy (HRT) on bone mineral density (BMD) in the lumbar spine. The 81 subjects were aged 40 to 64 years (mean ± SEM, 49.5 ± 0.6 years), and had received sequential or continuous HRT regimens, including 0.625mg of conjugated equine estrogen and 2.5 to 5mg of medroxy-progesterone acetate, for at least 3 years. Genomic DNA was extracted from blood cells, and analyzed for restriction fragment length polymorphism, using the restriction endonucleases Taq I, Apa I, and Fok I for VDR, and Pvu II and Xba I for ER. At 1 year, subjects with a Taq I genotype of TT (i.e., site absent) showed a significantly greater increase in BMD with treatment (BMD) than subjects with the Tt genotype (2.6 ± 0.5% vs –0.8 ± 1.4%; P = 0.016). A small difference between genotypes remained at 2 years (3.8 ± 0.6% vs 0.8 ± 1.6%; P = 0.069), but no significant difference between genotypes was seen at 3 years. In multiple regression analyses, BMD at 1 year was significantly affected by VDR-Taq I, Apa I, and ER-Pvu II genotypes and by age at treatment initiation, although at 3 years or more, BMD was significantly affected only by age. These results indicate that Taq I VDR gene polymorphism predicted the effect on lumbar BMD for the first year of HRT in Japanese women, and that the differences in BMD versus the polymorphism disappeared if the treatment was continued for over 2 years.     

雌激素受体基因多态性与骨密度及骨代谢关系的研究

目的研究中国健康绝经后妇女的雌激素受体estrogenreceptorER基因多态性与骨密度bonemineraldensityBMD、骨代谢的关系。方法选取246名中国健康绝经后妇女,年龄44～78岁,平均61岁。运用双能X线骨吸收法分别对其腰椎L1～4和股骨股骨颈N、Ward区W、大转子T的BMD进行测量,并用生物化学的方法测其血清中钙Ca、磷P、碱性磷酸酶ALP、甲状旁腺激素PTH和降钙素CT的含量,用分子生物学的方法分析内切酶PvuⅡ、XbaⅠ限制性片段长度多态性restrictionfragmentlengthpolymorphism,RFLP,观查ER基因多态性与BMD及骨代谢的关系。RFLP用PpPvuⅡ和Xx(XbaⅠ)来表示。结果PPxx基因型BMD明显低于其它基因型。结论ER基因RFLP与绝经后妇女BMD有关,此即为中国妇女绝经后骨质疏松症发病的原因。     

甲状旁腺素和维生素D受体基因多态对糖尿病患者骨密度的影响

目的探讨甲状旁腺素(PTH)基因多态性与中国北方汉族人糖尿病患者骨密度的关系,联合分析维生素D受体(VDR)基因和PTH基因多态性与骨密度的相关性。方法选自青岛市内分泌糖尿病医院1998年1月~2002年1月住院的糖尿病患者,运用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测了1型糖尿病(T1DM)组54例,2型糖尿病(T2DM)组104例,健康对照(CON)组102例,260例中国北方汉族人PTH基因多态性;采用双能X线吸收法骨密度仪(DEXA)测量骨密度。结果校正年龄和BMI后,1型糖尿病组腰椎、股骨颈骨密度低于对照组(P0.05);2型糖尿病组与对照组相比,骨密度差异无显著性(P0.05);甲状旁腺素(BSTB1位点)基因型和等位基因分布频率在1型糖尿病组、2型糖尿病组与对照组间差异无显著性(P0.05);在对照组及2型糖尿病组,BB基因型者腰椎(L2-4)和股骨颈部位骨密度显著高于Bb/bb基因型(P0.05);在1型糖尿病组,BB基因型仅腰椎L2-4部位骨密度高于Bb/bb基因型(P0.05);联合VDR基因多态(Apa I酶切位点)分析结果表明,Bbaa基因型在腰椎和股骨颈骨密度低于其他基因型(P0.05)。结论糖尿病患者PTH基因多态性(BSTB1位点)可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR基因多态(Apa I酶切位点)有助于识别糖尿病患者发生骨质疏松的高危人群。     

The association between vitamin D receptor gene polymorphisms and bone mineral density at the spine,hip and whole-body in premenopausal women

The genetic influence on bone mineral density (BMD) is thought to be mediated in part by alleles at the vitamin D receptor (VDR) locus. In order to assess the effect of VDR on BMD in premenopausal women, we studied 470 healthy white subjects, aged 44–50 years, participating in the Women's Healthy Lifestyle Project. Each participant was genotyped for theBsmI polymorphism at the VDR gene locus. BMD at the lumbar spine, hip and whole-body, and the whole-body soft tissue composition, were measured cross-sectionally using a Hologic QDR 2000 densitometer. The presence of a polymorphic restriction site at the VDR gene locus was specified asb, whereas absence of this site wasB. The frequency distribution of the VDR genotype was:bb, 20.6%;Bb, 39.1%; andBB, 40.2%. Spinal BMD (mean±SD) was significantly lower in women with VDR genotypeBB (1.038±0.11 g/cm²) as compared with those with genotypebb (1.069±0.12 g/cm²,p<0.05). Trochanter BMD was 2.7% lower in those with genotypeBB versusbb (0.685±0.10 g/cm² vs 0.708±0.09 g/cm²). A similar trend was shown at each subregion of the hip, but not at the whole-body. In premenopausal women, allelic status at the VDR locus contributed to variations in spinal and trochanteric BMDs, but the absolute difference in BMDs was small, amounting to 0.26 and 0.23 standard deviations, respectively. It is concluded that in this population of healthy premenopausal women there was a significant association between polymorphisms at the VDR gene locus and both spinal and trochanteric BMDs, yet no association was demonstrated for the whole-body BMD.     

Effect of vitamin D receptor and estrogen receptor gene polymorphism on the relationship between dietary calcium and bone mineral density in Japanese women

In a longitudinal analysis of the results of bone mineral density (BMD) screenings conducted in local communities, we examined the effect of lifestyle improvements on BMD and investigated the influence of allelic variations of the vitamin D receptor (VDR) and estrogen receptor (ER) genes. The subjects were 484 women (age, 24–80 years) who underwent BMD screenings at least twice between 1994 and 2002. We conducted BMD measurements of the lumbar spine by dual-energy X-ray absorptiometry and performed a simple questionnaire survey of lifestyle factors. Women receiving pharmacotherapy, or those with bone fractures, were excluded, leaving 338 women eligible for the study. They were retrospectively divided into three groups: (i) premenopause, women who were at least 5 years preceding menopause; (ii) perimenopause, women who were within 5 years before or after menopause; and (iii) postmenopause, women who were at least 5 years past menopause. There was no correlation at all between improvements of lifestyle factors (i.e., calcium intake from dairy products and time spent walking) and fluctuations in lumbar-spine BMD after 1, 3, or 5 years in the pre-, peri-, and postmenopausal groups. For women in the postmenopausal group, the PP genotype for the ER gene correlated with a significantly higher initial BMD than those with the Pp and pp genotypes (P = 0.04). After 3 years, presence of the TT genotype of Taq I of VDR gene polymorphism exhibited positive correlations (r = 0.29, P = 0.03) with the improvements in calcium intake and in lumbar spine BMD for the perimenopausal group, whereas the Tt genotype showed negative correlations (r = –0.48, P = 0.04). After 1, 3, and 5 years, presence of the Tt genotype showed a tendency toward a negative correlation with the increases in calcium intake and in lumbar spine BMD for the pre- and perimenopausal groups, although almost of these were not significantly different. In this study, we could not prove a positive correlation between the improvement of lifestyle and the fluctuation of BMD within a 5-year timeframe, although the polymorphisms within the VDR gene may have some influence.     

A fifteen-year longitudinal study in young adults on the relation of physical activity and fitness with the development of the bone mass: The Amsterdam Growth And Health Longitudinal Study

Although positive effects of physical activity are often reported, there are still uncertainties about the type, intensity, duration, and frequency of these activities that are most effective for (re)modeling bone mass during youth. In the Amsterdam Growth and Health Longitudinal Study, daily physical activity and fitness were monitored from age 13 to 29 years in a group of 182 males and females. At a mean age of 28 years, bone mineral density (BMD) was measured at three sites with dual X-ray absorptiometry (DXA): in the lumbar region (lumbar BMD), the femoral neck (hip BMD), and the distal radius (wrist BMD). Physical activity (PA) was estimated from a cross-check activity interview taking in consideration all daily physical activities during the last 3 months; PA was scored in two different ways: (1) metabolic physical activity score (METPA) by weighting the intensity (multiples of basic metabolic rate [METs]) and duration (minutes per week); and (2) mechanic physical activity score (MECHPA) by weighting the peak strain (ground reaction forces as multiples of body mass) irrespective of frequency and duration of the physical activities. Physical fitness was measured with a neuromotor fitness test (composite of six strength, flexibility, and speed tests) and as cardiopulmonary fitness (maximal oxygen uptake). The physical activity and fitness scores were calculated over two age periods: during adolescence (13–16 years) and during adulthood (21–27 years). The standardized regression coefficients (corrected for gender, biological age, body composition, and calcium intake) show that weight, physical activity (both METPA and MECHPA), and neuromotor fitness during adolescence and in young adulthood are significantly and positively related with the lumbar BMD (β = 0.11–0.40) and hip BMD (β = 0.18–0.26), measured at the mean age of 28 years. This was not the case for cardiorespiratory fitness. No significant correlations at all are found with wrist BMD, a bone site that is less involved in physical activity and fitness. It can be concluded that daily physical activity during adolescence and in the young adult period is significantly related to the BMD at the lumbar spine and femoral neck at age 28 of males and females. Only neuromotor fitness and not cardiopulmonary fitness during adolescence and young adulthood is related to the BMD of males and females at age 28 years.