Comparison of quantitative ultrasound of the phalanges with conventional bone densitometry in healthy postmenopausal women

The objective of this study was to evaluate the utility of the quantitative ultrasound (QUS) technique for the identification of subjects with spine fracture or low bone mineral density (BMD) previously determined by dual energy X-ray absorptiometry (DEXA). QUS of the phalanges in 1,350 postmenopausal women (60–83 years old) was compared with DEXA measurements of four skeletal sites (lumbar spine, total hip, femoral neck, and distal radius) of the same subjects. The contribution of body mass index (BMI) was also assessed. Amplitude dependent speed of sound (AD-SoS), ultrasound bone profile index (UBPI), and BMD of all anatomical regions, except for the spine, decreased significantly with increasing age quartiles. QUS parameters correlated weakly but significantly with BMD ( r =0.21–0.31, p <0.01). After adjustment for BMI, the association between QUS parameters and BMD remained unchanged. UBPI was found to be independent of BMI. All techniques and all sites were able to significantly discriminate fractured from non-fractured subjects by receiver operating characteristic (ROC) analysis (area under the curve [AUC]0.60, p <0.0001). AD-SoS and UBPI showed similar fracture discrimination ability of spine, distal radius and total body BMD in terms of odds ratios, but BMD of the total hip and femoral neck showed the best performance in discriminating fractured from non-fractured subjects. In conclusion, QUS assessment of the phalanges correlates moderately with BMD of all skeletal sites and is able to effectively discriminate fractured from non-fractured subjects.The authors wrote this article on behalf of the PERF study group     

Association between bone loss and promoter polymorphism in the <Emphasis Type="Italic">IL-6</Emphasis> gene in elderly Japanese women with hip fracture

 Recently, a G/C polymorphism was found at position −573 of the interleukin-6 (IL-6) gene promoter. We investigated how this genetic polymorphism relates to IL-6 production and osteoporosis in elderly Japanese women. Genomic DNA was extracted from an aliquot of monocytes in the bone marrow; the monocytes were simultaneously used to form osteoclast-like multinucleated cells (MNCs) and to produce IL-6. Of the 47 subjects with fractures, 96% had a C allele at position −573 of the IL-6 gene. Only 2 subjects possessed homozygotes of G at that position. We investigated IL-6 levels, MNC formation in bone marrow culture, and femoral neck bone mineral density (BMD) in the subjects with the GC and CC genotypes. There were no significant differences between these genotypes as regards IL-6 levels, MNC formation, and femoral neck BMD. However, in the CC genotype, there was a negative relationship between femoral neck BMD and IL-6 levels, and between femoral neck BMD and MNC formation, whereas in the GC genotype and combined (GC + CC) genotypes, femoral neck BMD tended to be related to IL-6 levels and MNC formation. Moreover, the stromal cells in the CC genotype showed higher IL-1α-stimulated IL-6 production than did the stromal cells in the GC genotype. Our findings suggest that important information might be obtained not only by continued comparison of different genotypes but also by comparative study within each particular genotype. Received: April 30, 2002 / Accepted: January 23, 2003 RID="*" ID="*" Offprint requests to: Y. Koshihara     

Leisure physical activity is associated with quantitative ultrasound measurements independently of bone mineral density in postmenopausal women

The purpose of this study was to assess the magnitude of the relationship between leisure physical activity and bone status as measured either by an Achilles^TM ultrasound bone densitometer (QUS) or dual-energy X-ray absorptiometry (DXA) in postmenopausal women. We studied 1162 French Canadian postmenopausal women, aged 33–84 years (mean age 58 years), for QUS parameters [broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI)] measured at the right calcaneus, and bone mineral density (BMD) measured at the lumbar spine and femoral neck. Multivariate regression analyses revealed that leisure physical activity level was an independent predictor of the heel QUS parameters and of femoral neck BMD. No such association was observed for BMD of the lumbar spine. Heel QUS parameters (BUA, SOS, SI) and femoral neck BMD adjusted for interfering covariables showed a statistically significant difference between sedentary (less than three sessions/month) and active women (three or more sessions/week) (P 0.001). Furthermore, after adjusting each heel QUS parameters for the mean lumbar spine BMD value, the association observed between leisure physical activity and QUS remained significant. These results suggest that regular leisure physical activity could influence QUS parameters, independently of BMD, and that quantitative ultrasound could be a suitable outcome measure in exercise studies in postmenopausal women.     

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.     

Assessment of the bone status of Nigerian women by ultrasound and biochemical markers

Ultrasound analysis of the calcaneus and serum markers of bone turnover were used to examine the bone status of healthy Nigerian women who reside in an area of the world where dietary calcium intake is generally low and estrogen replacement therapy is not widely available. A total of 218 women (108 premenopausal and 110 postmenopausal) between the ages of 16 and 95 years were enrolled in the study. Broadband ultrasound attenuation (BUA) and speed of sound velocity (SOS) were measured and used to calculate the stiffness index (SI) of the calcaneus. In this cross-sectional study, the Nigerian women exhibited a marked age-dependent decline in SI that was defined by the regression equation SI=105.9–6.62E-3×Age². SI was significantly correlated with age (r=−0.41,P<0.001) and with serum NTx concentrations (r=−0.26,P<0.001), but not with serum levels of bone specific alkaline phosphatase (BSAP). Years since menopause was also significantly correlated with SI (r=0.40,P<0.001). A significant increase in serum NTx concentration occurred at least a decade before a significant decline in SI was evident. In the total study group, 24% of the women had T-scores indicative of osteopenia and 9% had T-scores indicative of osteoporosis, based on US reference data. Although the reported current incidence of fracture is low in women in sub-Saharan West Africa, these data show that after menopause Nigerian women have a decline in bone quality and increase in bone turnover similar to North American Caucasian women.     

Bone density of the calcaneus and fractures in 75- and 80-year-old men and women

bone mineral density of the calcaneus in relation to fractures was studied both retrospectively and prospectively among the 75- and 80-year-old men and women resident in the city of Jyväskylä, Finland, in 1989 and 1990, respectively. The bone measurements were performed at the calcaneus by¹²⁵I-photon absorption. Retrospective fracture (RF) history after age 50 was collected by questionnaire and interview, and reported fractures were checked from medical records. In the retrospective study, in the 75-year-olds a fracture was found in 22% (n=22) of men and in 45% (n=84) of women. The corresponding figures for the 80-year-olds were 16% (n=9) and 35% (n=48). Over half of the fractures were of the wrist/hand or ankle/leg. Prospective fractures (PF) were recorded over periods of 29–34 months. Twenty of the 75-year-olds and 16 of the 80-year-olds sustained a fracture during the follow-up period. In the 75-year-olds, the results showed that both RF and PF women, together with the RF men, had lower bone area density (BMD_a) and volume density (BMD_v) than the non-fracture (NF) subjects (p=0.001–0.011). In the 80-year-olds, significantly lower BMD_a was found in the RF women (p=0.008) and lower BMD_v in the PF women (p=0.024) compared with the NF subjects. During the follow-up period there were no fractures in either of the sex or age groups among those with BMD_a and BMD_v values greater than 1 SD above the mean. When using logistic regression analysis, BMD_v alone explained about 60% of overall fracture probability among the women studied.     

Serum insulin-like growth factor-I level is associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes mellitus

Summary Multivariate logistic regression analysis showed that serum IGF-I level was significantly lower in postmenopausal diabetic women with vertebral fractures than in those without fractures. Serum IGF-I level could be clinically useful for assessing the risk of vertebral fractures independent of BMD in postmenopausal women with type 2 diabetes. Introduction We investigated the relationships among serum IGF-I and C-peptide levels, BMD, and vertebral fractures in postmenopausal women with type 2 diabetes. Methods A total of 131 postmenopausal women with type 2 diabetes were consecutively recruited, and radiographic and biochemical characteristics were collected. Results Either IGF-I or C-peptide was not correlated with BMD at any site or bone metabolic markers, such as osteocalcin (OC) and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX). However, serum IGF-I level was significantly lower in subjects with vertebral fractures than in those without fractures (mean ± SD: 106.9 ± 50.0 vs. 142.8 ± 50.8 ng/ml, p = 0.0006). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum IGF-I adjusted for the parameters described above as independent variables, IGF-I was selected as an index affecting the presence of vertebral fractures [odds ratio = 0.436, 95% confidential interval 0.234–0.814 per SD increase, p = 0.0092]. This significance was almost the same after additional adjustment for lumbar BMD or C-peptide. Conclusions Serum IGF-I level could be clinically useful for assessing the risk of vertebral fractures independent of BMD in postmenopausal women with type 2 diabetes.     

绝经后妇女桡骨远端骨折术后桡骨短缩与骨密度的相关性研究

目的分析绝经后妇女的骨密度与桡骨远端骨折术后出现桡骨短缩的相关性。方法回顾性分析自2012-01—2014-06行手术治疗的252例绝经妇女桡骨远端骨折,术后均达到解剖复位或基本达到解剖复位,获得1年完整随访。将术后3个月桡骨短缩距离4 mm的患者纳入观察组,其余的按年龄、骨折类型及绝经时间进行1∶1个体匹配,纳入与观察组同样数量的病例进入对照组(术后3个月桡骨短缩距离4 mm)。术前、术后3个月及术后6个月用双能X线骨密度仪对2组健侧桡骨进行骨密度测量。结果观察组骨密度值:术前(0.69±0.14)g/cm2,术后3个月(0.67±0.12)g/cm~2,术后6个月(0.62±0.10)g/cm~2。对照组骨密度值:术前(0.79±0.15)g/cm~2,术后3个月(0.76±0.13)g/cm~2,术后6个月(0.71±0.10)g/cm~2。2组骨密度值随时间增加而降低,且观察组术前(F=7.588,P=0.008)、术后3个月(F=8.520,P=0.005)、术后6个月(F=11.203,P=0.001)骨密度值均低于对照组,差异有统计学意义(P0.05)。结论对于桡骨远端骨折患者术后出现桡骨短缩的原因,骨密度降低是一个不容忽略的重要因素,在术后应重视对低骨密度的患者采取相应措施。     

Low bone mass is associated with carotid atherosclerosis in postmenopausal women: The Japanese Population-based Osteoporosis (JPOS) Cohort Study

Summary  We analyzed 609 women belonging to the JPOS study in a 10-year follow-up survey, to examine the association of osteoporosis with atherosclerosis. Osteoporosis or prevalent vertebral fracture at baseline was associated with increased intima-media thickness of the carotid bifurcation in postmenopausal women, adjusted for age, BMI, and other variables at baseline. Introduction  Whether low bone mass predicts increased carotid atherosclerosis has not been fully investigated. Methods  In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women ≥50 years old in 2006 without a history of cardiovascular or connective tissue diseases at baseline. BMD and evaluation of vertebral fracture at baseline were used. The intima-media thickness of carotid bifurcation (BIF-IMT) was measured by B-mode ultrasonography in 2006. Results  Adjusted BIF-IMT values of subjects with spine T-score ≥-1, between-2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19 mm, 1.34 mm, 1.57 mm, respectively, in women with less than 10 years since menopause (YSM) (n = 159), 1.30 mm, 1.32 mm, 1.53 mm, in women with YSM ≥10 without a history of hypertension at baseline (n = 144) (both with p < 0.05 for linear trend). Those values among no versus prevalent vertebral fracture in women with YSM ≥10 were 1.40 mm, 1.66 mm with p < 0.05 (n = 202). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for women with YSM < 10) at baseline. Conclusion  Osteoporosis including prevalent vertebral fracture may be associated with carotid atherosclerosis in the first 10 years of postmenopausal women.     

Ultrasound of the phalanges is not related to a previous fracture. A comparison between ultrasound of the phalanges, calcaneus, and DXA of the spine and hip in 75-year-old women.

Recently, an ultrasound (US) device for measurement of amplitude-dependent speed of sound in four proximal phalanges of the hand (DBM Sonic 1200, IGEA, Carpi, Mo, Italy) has been introduced but has not been thoroughly investigated in populations at most risk for fragility fractures (i.e., elderly women). As part of the Malm? Osteoporosis Prospective Risk Assessment study (OPRA), we investigated 1044 randomly selected women, all 75 yr of age, with US of the phalanges and, for comparison, also with two more established methods for bone mass measurement: US of the calcaneus and dual-energy X-ray absorptiometry (DXA) of the hip and spine, both methods having an ability to predict fracture. A self-assessment questionnaire was used to obtain information on previous fracture and age at fracture event. We found a low correlation between US of the phalanges and US of the calcaneus speed of sound (SoS) (r = 0.11, p < 0.01), US of the calcaneus (stiffness) (r = 0.09, p < 0.05), DXA of the femoral neck (r = 0.09, p < 0.05), and DXA of the spine (r = 0.10, p < 0.01) and no significant correlation between US of the phalanges and US of the calcaneus broadband ultrasound attenuation (BUA) and DXA trochanter. Also, no differences in US of the phalanges were found when comparing women without any fracture with women with at least one fracture, whereas US of the calcaneus (SoS, BUA, and stiffness) and DXA of the femoral neck, trochanter, and spine were all lower in the women with a fracture history (p < 0.0001). In addition, the precision of the US of the phalanges method was evaluated and found to be lower in these elderly women, compared to the precision reported by others and the manufacturer. In summary, the present data indicate that US of the phalanges is not a usable tool for estimating fracture risk in an elderly female population.     

绝经后女性股骨近端骨密度与骨质疏松性骨折相关性研究

目的：研究绝经后女性股骨近端骨密度的变化规律与骨质疏松症、骨质疏松性骨折间的关系。方法采用法国Medlink公司Osteocore 3型双能X线骨密度仪,对本地区417例绝经后女性股骨颈、大转子、粗隆间、全髋进行骨密度测定。结果骨折组各年龄段、各部位的BMD均比非骨折组低（ P＜0．05）。随着年龄的增长,股骨近端骨量逐渐丢失,除了45～50组,其余各年龄段骨折组的患病率明显高于非骨折组（ P＜0．05）,骨密度值越低,骨折危险性越大。结论绝经后女性股骨近端骨密度与发生骨质疏松性骨折的风险呈明显负相关性,应该注意预防。     

Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos)

Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.The authors wrote this article on behalf of the Camos Research Group.     

阿伦磷酸钠对绝经后2型糖尿病合并骨质疏松症患者骨代谢的影响

目的 探讨阿伦膦酸钠对绝经后2型糖尿病合并骨质疏松症患者骨代谢及骨密度的影响。方法 选择2012年1月至2013年1月在本院接受治疗的绝经后2型糖尿病合并骨质疏松症患者51例,给予阿伦膦酸钠治疗6个月。采用美国Norland双光能X线骨密度检测仪对所有患者进行腰椎L2-L4和左侧股骨近端（包括Neck、Troch、Ward三角区)骨密度测量,并测定身高、体重、空腹血糖(FBG)、HbAlc、PTH、OC、CTX、25（OH）VD、BALP等。对比治疗前后骨密度及骨代谢标志物变化。结果 用阿伦膦酸钠治疗6个月使绝经后2型糖尿病合并骨质疏松症患者的FBG、2hPG 、HbA1c降低,治疗前与治疗后相比较,差异有统计学意义（P〈0.05）。血Ca、P浓度治疗前与治疗后相比较,差异无统计学意义(P＞0.05)。骨代谢标志物CTX治疗前与治疗后相比,差异有统计学意义（P〈0.05）。OC 、PTH、BALP、25OHVD治疗前与治疗后相比较,差异无统计学意义(P>0.05)。治疗前腰椎和股骨颈骨密度与治疗后相比较,差异有统计学意义（P〈0.05）。Torch 、Ward部位骨密度治疗前与治疗后相比较,差异没有统计学意义(P＞0.05)。结论 阿伦膦酸钠治疗绝经后2型糖尿病合并骨质疏松症疗效明显,短时间内可改善骨代谢指标和提高腰椎骨密度。     

Effects of the interaction between lean tissue mass and estrogen receptor alpha gene polymorphism on bone mineral density in middle-aged and elderly Japanese

Because both genetic and environmental factors influence bone mass, it is important to examine the effect of gene-environment interactions on bone mineral density (BMD) for the prevention of osteoporosis at an individual level. Estrogen receptor alpha (ER alpha) plays an important role in increasing BMD via mechanical strain and muscle mass is a reflection of the forces the muscle applies to the bone. The aim of this study is to investigate the effect of the interaction between lean tissue mass (LTM) and the ER alpha polymorphisms T-->C (PvuII) [dbSNP: rs2234693] and A-->G (XbaI) [dbSNP: rs9340799] on BMD in middle-aged and elderly individuals. Subjects were 2209 community-dwelling Japanese men and women, ages 40 to 79 years. ER alpha polymorphisms in the first intron, T-->C and A-->G were identified and lumbar spine and femoral neck BMD and LTM were measured by dual-energy X-ray absorptiometry. Both T-->C and A-->G polymorphisms were divided into two genotype groups (TT vs. TC/CC; AA vs. AG/GG). In postmenopausal women, the effect of LTM on femoral neck BMD was significantly larger for those with the TC/CC genotype than for those with the TT genotype for the T-->C polymorphism, and larger for those with the AG/GG genotype than for those with the AA genotype for the A-->G polymorphism. This gene-LTM interaction was observed at the femoral neck, but not at the lumbar spine. For men and premenopausal women, no gene-LTM interaction was found. In conclusion, there was an interaction between LTM and the ER alpha T-->C and A-->G polymorphisms with respect to their effect on femoral neck BMD in postmenopausal women and those with the TC/CC and AG/GG genotypes had larger effects of LTM than those with TT and AA genotypes.     

Radiocalcium absorption is reduced in postmenopausal women with vertebral and most types of peripheral fractures

Intestinal calcium absorption accounts for 60% of the variance in calcium balance and is therefore a potentially very important determinant of bone status. Whether measured by the balance technique or with radiocalcium, it is known to be significantly reduced in postmenopausal women with vertebral and hip fractures. By contrast, there is very little information about calcium absorption in other types of postmenopausal fracture. We now report a series of 549 untreated, Caucasian postmenopausal women in whom we recorded prevalent fractures, measured radiocalcium absorption, and obtained radiographs of the lateral thoracic and lumbar spine. Of these women, 172 had no prevalent fractures, showed normal spine radiographs, and served as controls; 72 had one or more peripheral fractures but normal spine radiographs; 147 had one or more wedged or crushed vertebrae but no peripheral fractures; and 158 had a history of peripheral fracture and one or more fractured vertebrae. Age-adjusted radiocalcium absorption was significantly lower in the two groups with spinal fractures than in the controls (P<0.001) but not in the group with peripheral fractures only. It was also lower in the cases with more than two spinal fractures than in those with two or less (P<0.001). In respect of peripheral fractures, the greatest age-adjusted absorption deficit was found in fractures of the humerus (35%) followed by hip (32%), spine (21%), wrist (19%), and rib 17% (all significant but not significantly different from each other). Lesser deficits in tibia, ankle and foot fractures were not significant but type 2 errors could not be excluded. We conclude that impaired calcium absorption is particularly associated with those fractures for which osteoporosis is a significant risk factor.     

Association with replication between estrogen‐related receptor γ (ESRRγ) Polymorphisms and bone phenotypes in women of European ancestry

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen‐related receptor γ (ESRRγ) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRγ sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual‐energy X‐ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRγ in the determination of bone density in women. © 2010 American Society for Bone and Mineral Research     

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.     

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD

Osteoporosis is a common disease with a strong genetic component. Linkage studies have suggested linkage between BMD and loci on chromosome 1. The MTHFR gene is located on chromosome 1. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used for homocysteine methylation to methionine. The rare genotype (TT) of the C677T polymorphism has previously been demonstrated to be associated with increased plasma homocysteine levels in individuals with inadequate plasma folate levels. Recently, the TT genotype has been found to be associated with reduced bone mass. We therefore examined if the C677T polymorphism in the MTHFR gene is associated with changes in bone mass and risk of osteoporotic fractures in 388 osteoporotic patients and 336 normal individuals. The distributions of the genotypes CC, CT and TT in women with osteoporotic vertebral fractures and normal controls were 43.5%, 42.2% and 14.3% and 52.0%, 42.0% and 8.0%, respectively, ²=5.62, P=0.06. Since studies of the functionality of this polymorphism have revealed that only the TT genotype is associated with biochemical changes, we also compared the prevalence of the TT genotype versus the CT- and CC genotypes in patients and controls and found that the TT genotype is significantly more common in women with vertebral fractures (14.3%) compared with normal controls (8.0%), ²=4.31, P<0.05. Logistic regression analysis demonstrated that vertebral fractures were significantly associated with BMD (lumbar spine) and height but only marginally with the MTHFR genotype (P=0.06). Multiple linear regression analysis revealed that weight, age and the MTHFR polymorphism were predictors of lumbar spine BMD in women. However, age- and gender-corrected BMD of the lumbar spine and the hip was not significantly different between MTHFR genotypes. Furthermore, individuals with the TT genotype did not have BMD significantly lower than the combined group of individuals with the CT- or CC genotypes. In conclusion, we have demonstrated that the rare TT genotype of the C677T polymorphism in the MTHFR gene is associated with increased risk of osteoporotic fractures in women and a weak predictor of lumbar spine BMD.     

Objectively measured physical activity is associated with parameters of bone in 70-year-old men and women

As the world's population ages, the occurrence of osteoporosis-related fractures is projected to increase. Low areal bone mineral density (aBMD), a well-known risk factor for fractures, may be influenced by physical activity (PA). In this cross-sectional study, we aimed to investigate potential associations between objective measures of PA and bone properties, in a population-based cohort of 1228 70-year-old men and women. We measured volumetric BMD (vBMD, mg/cm³) together with cross-sectional area (CSA, mm²) by peripheral quantitative computed tomography at sites located 4% and 66% in the distal–proximal trajectory at the tibia and radius. We also measured aBMD (g/cm²) by dual energy X-ray absorptiometry at the femoral neck, lumbar spine (L1–L4) and radius. Participants wore triaxial accelerometers for 7 consecutive days to obtain objective estimates of PA. The intensity of the objective PA was divided into light (100–1951 counts/min [CPM]), moderate (1952–5724 cpm) and vigorous (≥ 5725 cpm). Maximal accelerations for the anterior–posterior (z), medio-lateral (x), and vertical (y) axes were also separately assessed. Associations were investigated using bivariate correlations and multiple linear regression, adjusted for height, weight and sex. Vigorous PA showed the strongest association with femoral neck aBMD (β = 0.09, p < 0.001), while both moderate and vigorous PAs were associated with cortical area and trabecular vBMD in the weight-bearing tibia (all p < 0.05). Peak vertical accelerations were associated significantly with cortical area (β = 0.09, p < 0.001) and trabecular vBMD (β = 0.09, p = 0.001) of the tibia, whereas peak anterior–posterior accelerations showed no correlation with these properties. No positive association was found between objectively measured PA and bone parameters of the radius. In conclusion, vertical accelerations and moderate to vigorous PA independently predict bone properties, especially in the weight-bearing tibia, in 70-year-old men and women.