Association of a single nucleotide variant in the human tumour necrosis factor alpha promoter region with decreased bone mineral density

Background : Tumour necrosis factor alpha (TNF &#102 ) has come to be regarded as a potential osteoporotic factor, because it has stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with oestrogen deficiency. We recently described genetic linkage between the TNF &#102 locus and human osteoporosis by sib-pair analysis. However, the molecular mechanism by which this locus regulates bone mineral density (BMD) remains unknown. Aim : We investigated whether the observed linkage reflects a sequence variation which might affect expression of the TNF &#102 gene or alter the function of TNF &#102 protein. Subjects and methods : We examined three single-nucleotide polymorphisms (SNPs) of the TNF &#102 gene in a group of 390 postmenopausal Japanese women living in northern Japan. Minor-allele frequencies for the three SNPs (-1031C, -863A and -857T) in this population were 0.16, 0.13 and 0.20, respectively. Results : Among the three SNPs examined, we observed a significant correlation only between the presence of a T allele at nt -1031 and decreased BMD, by analysis of variance. Among the three genotypic groups at nt -1031, mean BMD values were significantly higher in the T-negative genotype (C/C homozygotes; mean SD = 0.342 &#45 0.052 g cm -2 ), compared with T-positive genotypes (T/T homozygotes, 0.309 &#45 0.062 g cm -2; p = 0.0253 and T/C heterozygotes, 0.305 &#45 0.062 g cm -2 ; p = 0.0164). Conclusions : Given the lines of evidence from different genetic studies, we suggest that TNF &#102 may play a role in pathogenesis of osteoporosis.     

A nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density

Interleukin-6 (IL6) has come to be regarded as a potential osteoporotic factor because it has stimulatory effects on cells of the osteoclast lineage, and, thus, may play a role in the pathogenesis of bone loss associated with estrogen deficiency. We previously described association of the IL6 microsatellite with bone mineral density (BMD), as well as genetic linkage of the IL6 locus to human osteoporosis, by means of sib-pair analysis. However, the molecular mechanism by which this locus regulates BMD remains unknown. Accordingly, we searched for polymorphisms in the 5′ and 3′ flanking regions and in all five exons of the IL6 gene in a Japanese population sample. We identified three single-nucleotide sequence variations: a C/G substitution at nucleotide (nt) −634 in the promoter region, a G/A substitution at nt 4391 in the 3′ noncoding region, and a variation in the AnTn tract around nt −447. The last of these had already been observed in Caucasians, as well as in Japanese. The single-nucleotide polymorphism at −634 created a restriction site for the BsrBI endonuclease, and the frequency of the minor (G) allele was 0.184. Five haplotypes were constructed among three variations examined in the population. Linkage disequilibrium was observed between the variation at −634 and the variation at 4391, as well as between the variation at −634 and the AnTn tract variation. We found a significant correlation, in 470 subjects, between the presence of the G allele and decreased BMD, by analysis of variance. When BMD values were compared among the three genotypic groups (G/G, G/C, C/C) at nt −634, BMD was lowest among the G/G homozygotes (mean ± SD; 0.284 ± 0.062 g/cm²), highest among the C/C homozygotes (0.314 ± 0.059 g/cm²), and intermediate among the heterozygotes (0.303 ± 0.066 g/cm²; P < 0.05).Given the several lines of evidence from different genetic studies, we suggest that IL6 is, indeed, one of the genes affecting bone metabolism, in which variations can lead to osteoporosis. Received: November 8, 2000 / Accepted: February 5, 2001     

Association of the -381T/C promoter variation of the brain natriuretic peptide gene with low bone-mineral density and rapid postmenopausal bone loss

Osteoporosis is believed to result from interplay among multiple environmental and genetic determinants, including factors that regulate bone-mineral density (BMD). Recent quantitative trait locus analysis in human suggested a possible involvement of chromosomal region 1p36.2-p36.3 for determination of BMD. The brain natriuretic peptide (BNP, also named NPPB) gene lies within this candidate region for BMD determination. Overexpression of the BNP resulted in skeletal overgrowth in transgenic mice. Association analysis between nucleotide variations of the BNP gene and radial BMD in 378 Japanese postmenopausal women revealed a significant association of the -381T/C variation of the BNP gene with radial BMD (r = 0.17, P = 0.01). Homozygous T-allele carriers had the lowest BMD values (0.395 +/- 0.056 g/cm(2)), homozygous C-allele carriers had the highest (0.429 +/- 0.051 g/cm(2)), and heterozygous individuals had intermediate radial BMD values (0.405 +/- 0.048 g/cm(2)), indicating a dosage effect. Accelerated bone loss also correlated with the -381 T allele in a 5-year follow-up study (r = 0.21, P = 0.017). These results suggest that variation of BNP may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.     

Association of genetic variations of genes encoding thrombospondin, type 1, domain-containing 4 and 7A with low bone mineral density in Japanese women with osteoporosis

Twins and family studies have shown that genetic factors are important determinants of bone mass. Important aspects of bone mineral density (BMD) regulation are endocrine systems, notably hormonal regulation of adrenal corticoids, as indicated by clinical knowledge of glucocorticoid-induced osteoporosis. Glucocorticoid is known to negatively regulate bone mass in vivo, and glucocorticoid increases thrombospondin messenger ribonucleic acid (mRNA) levels. We studied single nucleotide polymorphisms (SNPs) in genes encoding thrombospondin, type 1, domain-containing 4 and 7A (THSD4 and THSD7A) for possible association with lumbar and femoral BMD among 337 Japanese women with osteoporosis who participated in the BioBank Japan project. Genetic variations of THSD4 and THSD7A loci displayed significant association with lumbar and femoral BMD. Most significant correlation was observed for THSD7A SNP rs12673692 with lumbar BMD (P = 0.00017). Homozygous carriers of the major (G) allele had the highest BMD [0.886 +/- 0.011 g/cm2, mean +/- standard deviation (SD)], whereas heterozygous carriers were intermediate (0.872 +/- 0.013 g/cm2) and homozygous A-allele carriers had the lowest (0.753 +/- 0.023 g/cm2). THSD4 SNP rs10851839 also displayed strong association with lumbar BMD (P = 0.0092). In addition, both THSD7A and THSD4 displayed significant association with femoral BMD in a recessive model (P = 0.036 and P = 0.0046, respectively). Results suggest that variations of THSD7A and THSD4 loci may be important determinants of osteoporosis in Japanese women.     

Haplotyping of TNFalpha gene promoter using melting temperature analysis: detection of a novel -856(G/A) mutation

Tumor necrosis factor alpha (TNFalpha) is a potent cytokine with a wide range of pro-inflammatory activities and plays a critical role in the pathogenesis of a number of infectious, inflammatory, autoimmune, and metabolic diseases. We determined four single-nucleotide polymorphisms (SNPs), -1031(C/T), -863(C/A), -857(C/T), and -308(G/A) in the TNFalpha promoter region using melting temperature analysis, among 1451 geriatric autopsy samples. Two adjacent SNPs, -863(C/A) and -857(C/T), were directly assayed by a single probe reaction, which correctly determined three of four expected haplotypes. Sequence confirmation related that the most rare haplotype (8/2902 chromosomes, frequency: 0.26%) contains a novel mutation of -856(G/A), instead of the predicted haplotype. These results indicate that melting temperature analysis provides a robust method to determine the polymorphisms in the TNFalpha promoter.     

Significant association between TNF-alpha (TNF) promoter allele (-1031C, -863C, and -857C) and cerebral malaria in Thailand

We examined a possible association of three single nucleotide polymorphisms (SNPs) of the tumor necrosis factor alpha (TNF) promoter -1031T>C (rs1799964), -863C>A (rs1800630), and -857C>T (rs1799724) with severe malaria in 466 adult patients having Plasmodium falciparum malaria in northwest Thailand. Four TNF promoter alleles comprising these three SNPs were detected in the studied population. The frequency of the TNF U04 allele designated -1031C, -863C, and -857C was found to be significantly greater in patients with cerebral malaria than in patients with mild malaria (12.6%, cerebral malaria vs 5.6%, mild malaria; odds ratio =2.5; P=0.002). The association of U04 with susceptibility to cerebral malaria was not caused by linkage disequilibrium with any specific HLA-B and -DRB1 alleles.     

Tumor necrosis factor-alpha promoter polymorphism is associated with the risk of Parkinson's disease.

Inflammatory events may contribute to the pathogenesis of Parkinson's disease (PD). We conducted a case-control study in a cohort of 369 PD cases and another cohort of 326 ethnically matched controls to investigate the association of tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphisms (SNPs) with the risk of PD. The overall genotype distribution at T-1031C and C-857T sites showed significant difference between PD cases and controls (P = 0.0062 and 0.0035, respectively). However, only the more frequent -1031 CC genotype was evidently associated with PD (P = 0.0085, odds ratio: 2.96; 95% CI: 1.38-7.09). Pairwise SNP linkage disequilibrium showed -1031 and -863 sites are in strong linkage disequilibrium (D' = 0.93, Delta(2) = 0.80). Pairwise haplotype analysis among the four sites showed that -1031C-863A may act as a risk haplotype among PD cases (P = 0.0028, odds ratio: 2.18; 95% CI: 1.33-3.69).     

Association between respiratory function and osteoporosis in pre- and postmenopausal women

OBJECTIVE: To investigate the relationships between respiratory function and osteoporosis, 132 premenopausal and 98 postmenopausal women were evaluated. METHODS: Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Pulmonary function and anthropometric parameters were measured using a spirometer and a body composition analyzer. RESULTS: Lumbar spine and proximal femur BMDs in postmenopausal women with forced expiratory volume in 1s (FEV1) > or = 92.0% averaged 0.83 +/- 0.12 g/cm2 and 0.67 +/- 0.11 g/cm2, which were significantly above the values (0.76 +/- 0.14 g/cm2 and 0.61 +/- 0.12 g/cm2, P < 0.05) in those with FEV1 <92.0%. The prevalences of osteoporosis at lumbar spine and proximal femur were 59.2 and 46.9% in the postmenopausal women with peak expiratory flow rate (PEFR) <5.12 l/s, significantly higher than those of osteoporosis at the corresponding sites in the women with > or = 5.12 l/s (36.7 and 20.4%, P < 0.05). Lumbar spine and proximal femur BMDs were positively correlated with FEV1 (r = 0.28, P < 0.05; r = 0.31, P < 0.05) and PEFR (r = 0.35, P < 0.05; r = 0.23, P < 0.05) in postmenopausal women; however, no significant correlations were observed in premenopausal women. CONCLUSION: Pulmonary function seems to be more closely associated with BMD in postmenopausal women than in premenopausal women. Poor respiratory function may be an indicator of postmenopausal women at increased risk of osteoporosis.     

A prospective,randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women

OBJECTIVES: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. METHODS: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. RESULTS: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively). CONCLUSION: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.     

Linkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their association with bone mass in perimenopausal women

Osteoporosis is a multifactorial disease with a strong genetic component characterized by reduced bone density and increased fracture risk. A candidate locus for regulation of hip bone mineral density (BMD) has been identified on chromosome 1p36 by linkage analysis. One of the positional and functional candidate genes located within this region is the tumour necrosis factor receptor superfamily member 1B (TNFRSF1B). In order to investigate whether allelic variation in TNFRSF1B contributes to regulation of bone mass, we studied several polymorphisms of this gene in a population based cohort study of 1240 perimenopausal women from the UK. We studied a T676G change in exon 6 (196: Met-Arg) and three SNPs (G593A, T598G, and T620C) in the 3'UTR of the gene. The 3'UTR SNPs were in strong linkage disequilibrium (LD) with each other (P<0.00001), and the exon 6 SNP was in LD with G593A and T598G (P<0.00001). We found no association between T676G alleles and BMD at the spine or hip. However, haplotype analysis showed that subjects homozygous for the A593-T598-C620 haplotype (n=85) had femoral neck BMD values 5.7% lower than those who did not carry the haplotype (n=1155; P<0.00008) and this remained significant after correcting for confounding factors and multiple testing (P<0.0009). Regression analysis showed that the ATC haplotype accounted for 1.2% of the population variance in hip BMD and was the second strongest predictor after body weight. In summary, our work supports the view that allelic variation in the 3'UTR of TNFRSF1B gene contributes to the genetic regulation of bone mass, with effects that are specific for femoral neck BMD.     

Three TNFalpha single nucleotide polymorphisms in the Japanese population

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) is an essential regulator of immune responses and is implicated to relate to several types of disease susceptibilities. Population information on polymorphisms is essential for the study of genetic diseases. AIM: To obtain accurate information about single nucleotide polymorphisms (SNPs) in the TNFalpha gene in the Japanese population. SUBJECTS AND METHODS: The entire TNFalpha gene was screened for SNPs by directly sequencing 48 chromosomes derived from 24 unrelated Japanese individuals. Allele frequencies of each polymorphism were determined and compared with those previously reported in other populations. RESULTS: Three SNPs, -308G/A at nt -308, IVS1 + 125G/A at nt 492 and IVS3 + 104G/A at nt 1359 were observed, of which one (IVS3 + 104G/A at nt 1359) was novel. In addition, allele frequencies of -308G/A were remarkably different from those presented in the NCBI dbSNP, indicating a significant ethnic difference. CONCLUSIONS: The polymorphisms and allele frequencies obtained in this study will be useful for genetic studies of common diseases such as osteoporosis and rheumatoid arthritis in the Japanese population.     

Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women

Recent studies suggest that bone loss occurs among HIV-infected women. This study examined the effects of reduced androgen levels, changes in weight, body composition, and menstrual dysfunction on bone mineral density (BMD) among 152 HIV-infected women characterized by normal weight (>90% ideal body weight [IBW], n = 124) and low weight (相似文献   

Expression characteristic and significance of interleukin-6, nuclear factor kappa beta, and bone formation markers in rat models of osteoporosis

The goal of this study was to investigate the expression levels of interleukin 6 (IL-6), nuclear factor kappa beta (NF-kappabeta), bone-specific alkaline phosphatase (BALP), and bone osteocalcin (BGP) in rats with osteoporosis and their significance in the pathogenesis of osteoporosis. In all, 60 adult female SD rats were divided randomly into 3 groups of 20 rats each: normal control group (control), sham-operated group (sham), and ovariectomized group (OVX). In 2, 3, 4, 5, and 6 months after surgery, 4 rats were randomized from each group for assays of BMD, IL-6, BALP, and BGP. Then, the rats were sacrificed for the detection of IL-6 and NF-kappabeta expression levels in bone tissue by quantitative real-time RT-PCR analysis. Compared with the sham (0.097 +/- 0.04 g/cm2, 0.097 +/- 0.01 g/cm2, 0.095 +/- 0.07 g/cm2) and control group (0.107 +/- 0.01 g/cm2, 0.103 +/- 0.07 g/cm2, 0.108 +/- 0.06 g/cm2), the BMD of rats in the OVX group was reduced remarkably in 4, 5, and 6 months (0.082 +/- 0.05 g/cm2, 0.073 +/- 0.02 g/cm2, 0.061 +/- 0.05 g/cm2, respectively; P < 0.01); the serum IL-6 level increased significantly from 2 to 6 months after surgery (P < 0.01); and the serum levels of BALP and BGP were greater at 4, 5, and 6 months (P < 0.05). The quantitative real-time RT-PCR analysis demonstrated that IL-6 and NF-kappabeta mRNA levels in OVX group increased in a time-dependent manner. Moreover, the IL-6, NF-kappabeta, BALP, and BGP levels were correlated negatively with the BMD. Meanwhile, a positive correlation was observed between IL-6 and NF-kappabeta. In conclusion, the expression levels of IL-6, NF-kappabeta, and bone formation markers may increase significantly in the osteoporosis rats. These molecules could play a role in the pathogenesis.     

Linkage disequilibrium and haplotype analysis among four novel single-nucleotide polymorphisms in the human leukemia inhibitory factor (LIF) gene

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine implicated in various pathological conditions, such as rheumatoid arthritis and osteoporosis. Despite the possible importance of LIF as a therapeutic target, little is known about the bioregulation of the human LIF gene. We here sequenced the entire structure of the LIF gene of 48 alleles in the Japanese population. These experiments identified four single-nucleotide polymorphisms (SNPs) and determined their allelic frequencies from a 48-allele sequence in the Japanese population. All four SNPs found in the LIF gene were located within exon 3, that is, a C/T at nucleotide (nt) position 3951, a C/G at nt position 4376, an A/C at nt position 4442, and a G/A at nt position 5961 (nucleotide numbering starts from the ATG start codon). Based on the genotypic data, we constructed four major haplotypes in the tested population. Two-way comparisons of SNPs revealed complete linkage disequilibrium between SNPs at positions 3951, 4376, and 4442. These results may prove to be useful as genetic markers for population-based disease-association studies in osteoporosis. Received: May 2, 2001 / Accepted: June 26, 2001     

肿瘤坏死因子α基因启动子区域-1031T/C多态与不稳定性心绞痛的相关性

目的 研究肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)基因启动子区域-1031T/C多态与汉族不稳定性心绞痛的相关性.方法 采用MALDI-TOF质谱检测方法,在299例不稳定性心绞痛患者和202名健康对照者中,对TNF-α基因启动子区域的T-1031C多态进行基因分型,并采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)法测定其血清浓度.结果 -1031T/C多态的基因型分布及其等位基因频率在两组间相比差异均无统计学意义(P>0.05).但在男性不稳定性心绞痛患者中,其CC、TC和TT基因型分布与对照组相比有统计学意义(P=0.032),男性CC+TC携带者,不稳定性心绞痛的发病危险是TT携带者的1.66倍(95%CI:1.040～2.659).其等位基因频率在两亚组间相比差异无统计学意义(P>0.05).不稳定性心绞痛组的血清TNF-α浓度明显高于对照组(P=0.028,尤其男性亚组P=0.013),TC基因型的血清TNF-α浓度高于其他基因型,但差异无统计学意义(P>0.05).结论 TNF-α基因启动子区域的-1031T/C多态可能与男性不稳定性心绞痛的发生相关,尤其是男性C等位基因携带者.     

MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis

MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.     

Is there an association between inhaled corticosteroids and bone density in postmenopausal women?

BACKGROUND: During the last decades, there has been increased concern about the association between oral corticosteroid (OC) therapy and osteoporosis. OBJECTIVE: The question currently discussed is whether inhaled corticosteroids (ICs) in recommended doses have any clinically relevant effects on bone mineral density (BMD). METHODS: We compared BMD in postmenopausal women exposed to corticosteroids only in inhaled form (IC group, n = 106) with that in women not exposed to corticosteroids (unexposed group, n = 674). BMD was also studied in 49 women exposed to OCs, intra-articular injections, or both in addition to ICs (OC group). The women were recruited from a population-based prospective cohort study. METHODS: We used a dietary survey, bone density measurement of the forearm, and a health questionnaire including an interview about past and present medication use. RESULTS: Mean BMD did not significantly differ between the IC group (0.434 g/cm2) and the unexposed group (0.429 g/cm2). The mean duration and dose of ICs was 8.2 +/- 5.03 years and 853 microg daily. Within the IC group, BMD stratified for cumulative dose of IC, duration, or current dose greater than or less than 1000 microg did not differ. BMD in the OC group was lower than that in the IC group (0.408 vs 0.434 g/cm2). CONCLUSION: No difference in BMD was noted between the IC group and unexposed control subjects, nor was any dose-response relationship observed between IC therapy and BMD.     

Elevated arterial stiffness in postmenopausal women with osteoporosis

OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are cardiovascular risk factors. We investigated the relationship between PWV and bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal women. The brachial-ankle PWV (baPWV) was measured using an automated device. The BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for age and years since menopause, women with osteoporosis had a significantly higher baPWV than those with normal BMD (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant differences in baPWV were seen between the osteoporotic and osteopenic groups or between the osteopenic and normal BMD groups. In univariate regression analysis, the baPWV was significantly negatively correlated with BMD (r = -0.450, P < 0.01), and significantly positively correlated with age (r = 0.601, P < 0.01), years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295, P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with other variables. In multivariate regression analysis, the baPWV was significantly correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis may have elevated arterial stiffness, suggesting that osteoporotic postmenopausal women may have a higher risk of cardiovascular disease.     

Associations between ABO blood groups and osteoporosis in postmenopausal women

To investigate whether any significant differences exist in the prevalence of osteoporosis in relation to ABO blood groups, 227 postmenopausal women were evaluated for bone mineral density (BMD), body composition, and anthropometric variables. There were no significant differences in age, anthropometric parameters, or body composition between women with O blood type and those with non-O blood types. However, lumbar spine and proximal femur BMDs in subjects with blood type O averaged 0.87+/-0.13 g/cm2 and 0.76+/-0.12 g/cm2, respectively, which were significantly above the values in those with non-O blood types (0.72+/-0.11 g/cm2 and 0.61+/-0.09 g/cm2, p<0.05, respectively). Among the ABO blood groups, the women with blood type AB showed the lowest BMDs (0.71+/-0.10 g/cm2 and 0.59+/-0.09 g/cm2) in the lumbar spine and proximal femur. The prevalences of osteoporosis in the proximal femur and lumbar spine averaged 2.3- and 1.7-fold higher in women with blood type AB than in those with blood type O. Thus, ABO blood group status seems to have a significant relationship to the prevalence of osteoporosis in postmenopausal women.     

Bone mineral density in collegiate female athletes: comparisons among sports

CONTEXT: Some female athletes may have decreased bone mineral density (BMD), which puts them at higher risk for stress fractures and future osteoporosis. OBJECTIVE: To compare site-specific BMD among National Collegiate Athletic Association Division I varsity female athletes and to determine predictor variables of BMD measurements. DESIGN: Between-groups design. SETTING: University health care system. PATIENTS OR OTHER PARTICIPANTS: All women varsity athletes were invited to participate in a cross-sectional study. Of 12 sports, we obtained complete data from 99 women (mean age = 20.2 +/- 1.3 years) representing gymnastics, softball, cross-country, track, field hockey, soccer, crew, and swimming/diving. MAIN OUTCOME MEASURE(S): Each participant was weighed, measured, and questioned about her menstrual status. Using dual-energy x-ray absorptiometry, we measured total-body BMD and region-of-interest scores for lumbar spine, pelvis, and average leg (average from right and left leg measurements) BMD. Using analyses of covariance, we compared BMD measurements among sports at each site while controlling for menstrual status and mass, and we performed a stepwise regression analysis to determine significant predictors of BMD at each site. RESULTS: Twenty-three athletes were oligomenorrheic or amenorrheic. Runners had the lowest total-body (1.079 +/- 0.055 g.cm (-2)) and site-specific ( P < .01) BMD values for every site except average leg score when compared with gymnasts and softball players. Swimmers and divers had significantly lower average leg BMD (1.117 +/- 0.086 g.cm (-2)) than athletes in every other sport except runners and rowers ( P < .01). Regression analysis revealed only mass and sport as significant predictors of total-body BMD. CONCLUSIONS: Runners and swimmers and divers demonstrated some deficits in site-specific BMD values when compared with athletes in other sports. When treating a female varsity athlete, athletic trainers should consider her mass and sport type with regard to her bone health.