SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women

Osteoporosis is a major public health problem, mainly quantified by low BMD. Eleven polymorphisms were investigated in this study; TNFalpha-857 (rs1799724), TGFbeta1-509 (rs1800469), osteocalcin (rs1800247), TNFalpha-308 (rs1800629), PTH BstB I (rs6254), PTH Dra II (rs6256), IL-1ra (VNTR), HSP70 hom (rs2227956), HSP 70-2 (rs1061581), CTR (rs1801197), and BMP-4 (rs17563). The relationship between the combined polymorphisms in different genomic regions and BMD variation was investigated. Among the female subjects, the proportion of subjects with low BMD in low BMI group (< or = 18.50) was significantly higher than that of the middle (18.51-22.99) and high (> or = 23.00) BMI groups (P < 0.05). In post-menopausal women, there was a significant association between low BMD and genotypes ranging from 2 to approximately 7 SNPs. For two combined SNPs, the portion of subjects with low BMD was significantly higher in those with CC-AA genotypes in rs1799724-rs1800629, compared to those with non-CC-AA genotypes in post-menopausal women and the combination of all women. Similarly, part of the combined SNPs with rs1799724-rs1800629-rs6254-rs6256-IL-1ra-rs2227956-rs1801197 was significantly associated with reduced BMD. After controlling for age and BMI, post-menopausal women with certain specific SNP combination had a 3.54- to 4.68-fold increased risk for low BMD, comparing to other SNP combinations. In conclusion, our data suggest that several gene polymorphisms may be cooperatively involved in the development of osteoporosis.     

CYP19A1 polymorphisms are associated with bone mineral density in Chinese men

Aromatase-dependent biosynthesis of estrogen plays an important role in maintenance of the male skeleton, and Cytochrome p450 aromatase is the key enzyme to catalyze the conversion of androgen precursors to estrogens. We investigated the association of polymorphisms in the CYP19A1 gene and bone mineral density in a Chinese cohort. 2392 extreme low femoral neck BMD cases or extreme high femoral neck BMD controls were selected from a population-based cohort and genotyped for eight SNPs in the CYP19A1 gene. Significant associations for rs17703883, rs12594287 and rs16964201 SNPs with BMD were found in men only. Men with TC/CC genotypes in the rs17703883 SNP had a 1.5 times higher risk of having extreme low femoral neck BMD (P = 0.003, empirical P value = 0.05), and decreased BMDs at total body (P = 0.004, empirical P value = 0.07) and total hip (P = 0.003, empirical P value = 0.05). Men carrying AA/AG genotypes in the rs12594287 SNP had a 30% reduced risk of having extreme low femoral neck BMD (P = 0.007, empirical P value = 0.12), and increased BMDs at total body (P = 0.0009, empirical P value = 0.018) and total hip (P = 0.001, empirical P value = 0.02). Men carrying TT/TC genotypes in the rs16964201 SNP had a 40% reduced risk of having extreme low femoral neck BMD (P = 0.005, empirical P value = 0.087), and increased BMDs at total body (P = 0.0001, empirical P value = 0.002) and total hip (P = 0.0006, empirical P value = 0.012). Haplotype analysis showed that the G-C-T-A-T haplotype was significantly related to higher BMD. Our finding suggests that genetic variations in the CYP19A1 gene are significantly associated with BMD at different skeletal sites in adult men, but not in women.     

Common genetic variants are associated with accelerated bone mineral density loss after hematopoietic cell transplantation

Background

Bone mineral density (BMD) loss commonly occurs after hematopoietic cell transplantation (HCT). Hypothesizing that genetic variants may influence post-HCT BMD loss, we conducted a prospective study to examine the associations of single nucleotide polymorphisms (SNP) in bone metabolism pathways and acute BMD loss after HCT.

Methods and Findings

We genotyped 122 SNPs in 45 genes in bone metabolism pathways among 121 autologous and allogeneic HCT patients. BMD changes from pre-HCT to day +100 post-HCT were analyzed in relation to these SNPs in linear regression models. After controlling for clinical risk factors, we identified 16 SNPs associated with spinal or femoral BMD loss following HCT, three of which have been previously implicated in genome-wide association studies of bone phenotypes, including rs2075555 in COL1A1, rs9594738 in RANKL, and rs4870044 in ESR1. When multiple SNPs were considered simultaneously, they explained 5–35% of the variance in post-HCT BMD loss. There was a significant trend between the number of risk alleles and the magnitude of BMD loss, with patients carrying the most risk alleles having the greatest loss.

Conclusion

Our data provide the first evidence that common genetic variants play an important role in BMD loss among HCT patients similar to age-related BMD loss in the general population. This infers that the mechanism for post-HCT bone loss is a normal aging process that is accelerated during HCT. A limitation of our study comes from its small patient population; hence future larger studies are warranted to validate our findings.     

Adiponectin is associated with bone mineral density in perimenopausal women.

The aim of the current investigation was to investigate any potential effect of fasting plasma adiponectin concentration on bone tissue, and to find possible relationships of fasting plasma adiponectin level with different body composition, insulin sensitivity and physical performance parameters in a group of healthy perimenopausal women. Twenty-one premenopausal and 17 early postmenopausal women participated in this study. The women were matched for body mass index (BMI) and level of mean daily energy expenditure. Women had similar adiponectin (8.4 +/- 3.9 vs. 9.9 +/- 5.4 microg/ml) and leptin values (12.0 +/- 7.7 vs. 14.0 +/- 8.2 ng/ml) before and after menopause. Significant relationships were observed between plasma adiponectin and bone mineral content, total bone mineral density (BMD) and lumbar spine BMD values (r > - 0.36; p < 0.05). Furthermore, adiponectin had a significant negative association with total BMD (beta = - 1.228; p = 0.004) and lumbar spine BMD (beta = - 0.312; p = 0.005) independent of the influence that other measured body compositional, hormonal or physical performance factors may exert on BMD. Adiponectin was also significantly related to waist-to-hip ratio (WHR) (beta = - 2.300; p = 0.002) and fasting insulin resistance index (FIRI) (beta = - 0.006; p = 0.007) in separate regression models. No relationship was observed between leptin and measured bone, physical performance and insulin resistance values. Leptin significantly correlated to BMI (beta = 0.018; p = 0.034), lean body mass (beta = 0.025; p = 0.024) and fat mass (beta = 0.019; p = 0.001) in separate regression models. In conclusion, the results of present study show that circulating adiponectin appears to exert an independent effect on BMD in perimenopausal women and may represent a link between adipose tissue and bone mineral density.     

Low selenium levels are associated with decreased bone mineral densities

PurposeOsteoporosis has a high worldwide prevalence and detrimental consequences (e.g., increased fracture risk). The amount of bone mineral in bone tissue (i.e., bone mineral density [BMD]) is most widely used indicator of osteoporosis in clinical medicine. Selenium is an essential micronutrient for animals and humans. It is a cofactor for antioxidant enzyme reduction (e.g., glutathione peroxidase). It also enhances immune surveillance and modulates cell proliferation. Study findings on the associations between BMD and selenium levels are inadequate and contradictory. The purpose of this study was to examine the associations between hair selenium levels and lumbar spine and femur BMD values.MethodsUsing a cross-sectional study design, we assessed the associations between hair selenium levels and BMD values in 1,167 Korean adults who underwent a health check-up. Each subject was assigned to one of two groups based on BMD (normal group [T-score ≥ -1.0] or low BMD group [T-score < -1.0]). The associations between hair selenium levels and the risk for low BMD were estimated using multivariate logistic regression models.ResultsStudy participants with lower hair selenium levels were older and had higher phosphorous, alkaline phosphatase, and osteocalcin levels. They also had lower BMDs, corrected serum calcium levels, uric acid levels, and creatinine clearance. Participants with low BMDs had significantly lower hair selenium levels (P < 0.001). After adjusting for osteoporosis-related risk factors, the risk of a low BMD was significantly greater for the lower hair selenium quartile groups (P = 0.045).ConclusionIn conclusion, this study found that lower hair selenium levels were associated with low BMD values, independent of the other osteoporosis risk factors examined. Further prospective studies are warranted to determine the role of selenium in the development of osteoporosis.     

A genome-wide scan for loci linked to forearm bone mineral density

Osteoporosis is a chronic disorder characterized by low bone mass and fragility fractures. It affects more than 25 million men and women in the United States alone. Although several candidate genes, such as the vitamin-D-receptor gene or the estrogen-receptor gene, have been suggested in the pathogenesis of osteoporosis, the genetic dissection of this disorder remains a daunting task. To search systematically for chromosomal regions containing genes that regulate bone mineral density (BMD), we scanned the entire autosomal genome by using 367 polymorphic markers among 218 individuals (153 sibpairs) from 96 nuclear families collected from three townships of Anqing, China. In these 96 families, DNA samples from both parents were available for 82 (85.4%) families. By using age- and gender-adjusted forearm BMD measurements, a peak on chromosome 2 near D2S2141, D2S1400, and D2S405, a region previously linked to spinal BMD, showed evidence of linkage to both proximal and distal forearm BMD (multipoint LOD=2.15 and 2.14 for proximal and distal forearm BMD, respectively). One region on chromosome 13 (multipoint LOD=1.67) in the proximity of D13S788 and D13S800 showed evidence of linkage to distal forearm BMD only. Possible candidate genes included CALM2 (calmodulin 2) at 2p21.3-p21.1, a putative STK (serine/threonine kinase) at 2p23–24, POMC (pro-opiomelanocortin) at 2p23.3, and COL4A1 and COL4A2 (collagen IV alpha-1 and alpha-2 subunits) at 13q34. Because of the limited sample size, the suggestive evidence of linkage of this study should be considered as tentative and needs to be replicated in other larger populations. Received: 19 November 1998 / Accepted: 22 January 1999     

Alpine skiing is associated with higher femoral neck bone mineral density

Objective:

To evaluate the influence of elite-level alpine skiing on athletes’ skeleton.

Methods:

Thirteen professional alpine skiers (9 males and 4 females with mean age of 22.6 years) and their age- and height matched control subjects were measured with dual energy X-ray absorptiometry (total body, lumbar spine, proximal femur, forearm) and quantitative ultrasound (hand).

Results:

After adjusting for sex, age, weight and height, between-group differences were 15% (p=0.012) for the lumbar spine, 14% (p=0.022) for the femoral neck, 10% (p=0.051) for the total hip, and 11% (p=0.001) for the total body favoring the alpine skiers. However, after controlling for total body lean mass (~muscle mass), the group-differences lost their statistical significance, the borderline 10% difference (p=0.051) in femoral neck BMD excluded.

Conclusion:

Factors contributing to the alpine skiers’ higher BMD may not only include the greater muscle mass (~stronger muscles) of these athletes but also a large number of impacts and possibly other high-frequency features in external loading generated by the high-speed skiing performance.     

IgG glycan patterns are associated with type 2 diabetes in independent European populations

BackgroundType 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.MethodsIn the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.ResultsAfter correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.ConclusionsSeveral IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.General significanceThis work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.     

Genetic variants in the RELN gene are associated with otosclerosis in multiple European populations

Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is considered a complex disease caused by both genetic and environmental factors. In a previous study, we identified a region on chr7q22.1 located in the RELN gene that is associated with otosclerosis in Belgian–Dutch and French populations. Evidence for allelic heterogeneity was found in this chromosomal region in the form of two independent signals. To confirm this finding, we have completed a replication study that includes four additional populations from Europe (1,141 total samples). Several SNPs in this region replicated in these populations separately. While the power to detect significant association in each population is small, when all four populations are combined, six of seven SNPs replicate and show an effect in the same direction as in the previous populations. We also confirmed the presence of allelic heterogeneity in this region. These data further implicate RELN in the pathogenesis of otosclerosis. Functional research is warranted to determine the pathways through which RELN acts in the pathogenesis of otosclerosis.     

Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations

MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log₁₀(Bayes factor) ≥ 8.07] and for gondoic acid at FADS1/2 and GCKR [log₁₀(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology.     

Polymorphic microsatellite loci in the European rabbit (Oryctolagus cuniculus) are also amplified in other lagomorph species

Six polymorphic microsatellite markers developed for the European wild rabbit ( Oryctolagus cuniculus ) were amplified with 20 other species of lagomorphs, representing both commercially important species and species important from a conservation perspective. Successful amplification of a number of these loci has provided an important set of new molecular markers for this mammalian order.     

Quantitative trait loci,genes, and polymorphisms that regulate bone mineral density in mouse

This is an in silico analysis of data available from genome-wide scans. Through analysis of QTL, genes and polymorphisms that regulate BMD, we identified 82 BMD QTL, 191 BMD-associated (BMDA) genes, and 83 genes containing known BMD-associated polymorphisms (BMDAP). The catalogue of all BMDA/BMDAP genes and relevant literatures are provided. In total, there are substantially more BMDA/BMDAP genes in regions of the genome where QTL have been identified than in non-QTL regions. Among 191 BMDA genes and 83 BMDAP genes, 133 and 58 are localized in QTL regions, respectively. The difference was still noticeable for the chromosome distribution of these genes between QTL and non-QTL regions. These results have allowed us to generate an integrative profile of QTL, genes, polymorphisms that determine BMD. These data could facilitate more rapid and comprehensive identification of causal genes underlying the determination of BMD in mouse and provide new insights into how BMD is regulated in humans.     

Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men

In order to assess the contribution of polymorphisms in the RANKL (TNFSF11), RANK (TNFRSF11A) and OPG (TNFRSF11B) genes to variations in bone mineral density (BMD), a population-based cohort with 1,120 extreme low hip BMD cases or extreme high hip BMD controls was genotyped on five SNPs. We further explored the associations between these genetic variations and forearm BMDs by genotyping 266 offspring and 309 available parents from 160 nuclear families. A family-based association test was used. Significantly positive associations were found for A163G polymorphisms in the promoter regions of the OPG gene, a missense substitution in exon 7 (Ala192Val) of the RANK gene and rs9594782 SNP in the 5′ UTR of the RANKL gene with BMD in men only. Men with TC/CC genotypes of the rs9594782 SNP had a 2.1 times higher risk of extremely low hip BMD (P=0.004), and lower whole body BMD (P<0.001). Subjects with the TC genotype of the Ala192Val polymorphism had a 40% reduced risk of having extremely low hip BMD (P<0.01), and higher whole body BMD (P<0.01). Subjects with the GG genotype of the A163G polymorphism had a 70% reduced risk of having extremely low hip BMD (P<0.05), and higher whole body BMD (P<0.01). Significant gene–gene interactions were also observed among the OPG, RANK and RANKL genes. Our findings suggest that genetic variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are strongly associated with BMD at different skeletal sites in adult men, but not in women. Electronic Supplementary Material Supplementary material is available for this article at     

The ESR2 AluI gene polymorphism is associated with bone mineral density in postmenopausal women

Multiple factors may contribute to the pathogenesis of postmenopausal osteoporosis including environmental, life-style and genetic factors. Common variants in ESR2 gene encoding for ER-beta, highly expressed in bone tissue, have recently been proposed as candidates for affecting bone phenotype at the population level, particularly in postmenopausal women. In this study, we examined the genetic background at ESR2 AluI (rs4986938, 1730G>A) locus in 89 osteopenic, postmenopausal women (age range 49-56 years) together with BMD at lumbar spine and femoral neck sites as well as variations in plasma levels of bone metabolism and turnover markers. Genotyping for ESR2 G1730A polymorphism showed that the frequency of A mutated allele accounted for 0.4 in our cohort of postmenopausal women; moreover, the GA1730 heterozygous individuals were the most represented (50.6%) compared with GG (37.8%) and AA homozygous ones (14.6%). A regression analysis showed that lumbar spine BMD values were significantly associated with both ESR2 AA1730 genotype (p=0.044) and time since the onset of menopause (p=0.031), while no significant association was detected between biochemical markers and genetic background. Interestingly, 85% of patients with AA1730 genotype presented the smallest lumbar spine BMD values. These findings first indicate a worsening effect of ESR2 AluI polymorphism on lumbar spine BMD reduction in postmenopause, suggesting that the detection of this ESR2 variant should be recommended in postmenopausal women, particularly in populations with a high prevalence of ESR2 AA1730 homozygous genotype.     

The association between major depressive disorder,use of antidepressants and bone mineral density (BMD) in men

Objective:

Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men.

Methods:

Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression.

Results:

Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site).

Conclusions:

Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.     

Factors regulating circulating vascular endothelial growth factor (VEGF): Association with bone mineral density (BMD) in post-menopausal osteoporosis

Vascular endothelial growth factor (VEGF) plays an important role in bone health. We investigated the factors which influence circulating VEGF and their association with bone mineral density (BMD). Two hundred and fifty two post-menopausal women aged 64.5 [9.2] years were studied. BMD was determined at the lumbar spine (LS), femoral neck (FN) and total hip (TH). Serum oestradiol and VEGF were measured. Subjects were genotyped for two polymorphic variants in the 5′ untranslated region of the VEGF gene; G(634)C and C(936)T. Positive correlations were seen between circulating VEGF and BMI (r = 0.2, p < 0.02) and oestradiol (r = 0.25, p < 0.001). Following multi-linear regression analysis, serum VEGF was associated with the G(634) polymorphism (p = 0.08) and dietary calcium intake (p = 0.02). The association with calcium intake may be mediated by PTH as suggested by the in vitro studies. Following correction for confounders, there was no association between circulating VEGF and BMD at any site. Both VEGF polymorphisms were significant predictors of LS BMD G(634)C: p = 0.017 and C(936)T: p = 0.05. Circulating VEGF may be influenced by genetic, environmental and endocrine factors. Polymorphic variants in the VEGF gene are associated with spine BMD. Further larger studies are needed.     

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

Purpose

Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD_a) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.

Methods

Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40–79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.

Results

2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD_a, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD_a and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.

Conclusions

Our data replicate previous associations found between SNPs in the 6q25 locus and BMD_a at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.     

Cholesterol-rich low density lipoproteins are also more oxidized

Cardiovascular diseases are accompanied by active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using oxidized low-density lipoprotein (oxLDL) as a new diagnostic biomarker. Epidemiological study in populations of Estonia (782 subjects) and Russia (1433 subjects) was carried out in 2007-2009. The screening procedure included standard epidemiological methods. Oxidative stress was assessed by measuring the level of oxLDL using immunoassay method. Positive correlation between the levels of oxLDL and LDL cholesterol was indicated in blood of patients from estonian (r = 0.61; P < 0.05) and russian (r = 0.56; P < 0.05) populations. In russian population oxLDL/HDL cholesterol ratio was higher in the groups with highest risk of atherosclerosis development or manifest coronary artery disease (CAD). Cholesterol-rich low density lipoproteins are also more oxidized. Estimation of oxLDL/HDL ratio may be used as an independent biochemical marker for atherosclerosis.     

Measurement of bone mineral density (BMD) with quantitative computed tomography (QCT) in postmenopausal osteoporosis: effect of estrogen.

To determine the efficacy of the estrogen replacement therapy (ERT) on the bone mineral density (BMD) measured with quantitative computed tomography (QCT) in postmenopausal osteoporosis 16 women aged 46-72 were examined. They were divided into two groups: 8 women treated with conjugated estrogens (Group I) and 8 who did not received ERT (Group II). In all 16 patients the serum hormonal concentrations (LH, FSH and estradiol) were measured with radioimmunological methods. The bone densitometry was performed in all of them using the single-energy computed tomography (QCT) with the computer Picker 1200. Bone mineral density was measured in three lumbar vertebra (L1-L3) and expressed in milligrams K2HPO4 per ml. The bone mineral density (BMD) was statistically significantly higher in the estrogen treated group (Group I) in every vertebra compared with that of controls (Group II). The serum FSH concentration was statistically significantly lower in the ERT group (Group I) and a statistically significant correlation between FSH level and average BMD (Lmean) was present. In conclusion: 1. the ERT is very efficacious in preventing bone loss in postmenopausal women; 2. measurement of BMD in lumbar vertebra L1 or L3 may be a sufficiently reliable and accurate, cost-effective and time-saving method of screening for osteoporosis; 3. the serum FSH determination seems to be useful in monitoring of the estrogen therapy for postmenopausal osteoporosis.     

Subclinical hypervitaminosis A in rat: measurements of bone mineral density (BMD) do not reveal adverse skeletal changes

We have previously shown that subclinical hypervitaminosis A in rats causes fragile bones. To begin to investigate possible mechanisms for Vitamin A action we extended our previous study. Forty-five mature female Sprague-Dawley rats were divided into three groups, each with 15 animals. They were fed a standard diet containing 12IU Vitamin A per g pellet (control, C), or a standard diet supplemented with 120 IU ("10xC") or 600 IU ("50xC") Vitamin A/g pellet for 12 weeks. At the end of the study, serum retinyl esters were elevated 4- and 20-fold. Although neither average food intake nor final body weights were significantly different between groups, a dose-dependent reduction in serum levels of Vitamin D and E, but not Vitamin K, was found. In the 50xC-group the length of the humerus was the same as in controls, but the diameter was reduced (-4.1%, p<0.05). Peripheral quantitative computed tomography (pQCT) at the diaphysis showed that bone mineral density (BMD) was unchanged and that periosteal circumference had decreased significantly (-3.7%, p<0.05). Ash weight of the humerus was not affected, but since bone volume decreased, volumetric BMD, as measured by the bone ash method, even increased (+2.5%, p<0.05). In conclusion, interference with other fat-soluble Vitamins is a possible indirect mechanism of Vitamin A action. Moreover, BMD measurements do not reveal early adverse skeletal changes induced by moderate excesses of Vitamin A in rats. Since the WHO criterium for osteoporosis is based on BMD, further studies are warranted to examine whether this is also true in humans.