Postmenopausal Bone Mass Research Articles

The Gut Microbiome and Female Health.

The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: "gut microbiome", "estrogen", "menopause", "polycystic ovarian syndrome", "pregnancy", and "menstruation". In polycystic ovarian syndrome (PCOS), the abundance of Bacteroides vulgatus, Firmicutes, Streptococcus, and the ratio of Escherichia/Shigella was found to be increased while that of Tenericutes ML615J-28, Tenericutes 124-7, Akkermansia, Ruminococcaceae, and Bacteroidetes S24-7 was reduced. In breast cancer, the abundance of Clostridiales was enhanced, while in cervical cancer, Prevotella, Porphyromonas, and Dialister were enhanced but Bacteroides, Alistipes, and members of Lachnospiracea, were decreased. In ovarian cancer, Prevotella abundance was increased. Interestingly, the administration of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum ameliorated PCOS symptoms while that of a mix of Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus brevis W63, Bifidobacterium lactis W52, Lactobacillus salivarius W24, Lactobacillus acidophilus W37, Lactococcus lactis W19, Lactobacillus casei W56, and Lactococcus lactis W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, Prevotella maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.

AB0362 B-Cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) in Postmenopausal Rheumatoid Arthritis Patients with Low Bone Mass: A Possible Protective Role of Hydroxychloroquine

BackgroundThe increasing role of B-cells in the pathogenesis and management of RA, the common occurrence of postmenopausal osteoporosis with RA and the suggested responsibility of BAFF in autoantibodies production with...

Body fat distribution is associated with lumbar spine bone density independently of body weight in postmenopausal women

ObjectiveTo assess the association between the body fat distribution and axial bone mineral density (BMD) in postmenopausal women with or without hormone replacement therapy (HRT). DesignCross-sectional population-based study. SettingUniversity of Eastern Finland, Bone and Cartilage Research Unit, Kuopio, Finland. Population198 postmenopausal women, mean age 67.5 (1.9 SD), mean BMI 27.1 (3.9 SD). MethodsRegional body composition and BMD assessed by dual X-ray absorptiometry (DXA, Prodigy). Main outcome measuresSpinal and Femoral BMD. ResultsOut of the body composition parameters, FM was the main determinant of postmenopausal bone mass. Only the lumbar spine (L2–L4) BMD, not the femoral neck BMD, was positively associated with the trunk FM. Positive trends for association were revealed between the spinal BMD and the trunk FM regardless of the use of HRT. Adjustments did not change the results. ConclusionsHigher trunk fat mass was associated with the spinal BMD, but not with the hip BMD in postmenopausal women, irrespective of the HRT use. In addition to biological factors, uncertainties related to DXA measurements in patients with varying body mass may contribute to this phenomenon.

Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk

One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped for the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gen. We found that the -1997T allele and a haplotype containing it were associated with reduced bone mineral density (BMD) and increased bone turnover at menopause and after 10 years of follow-up. We wanted to investigate whether the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gene are associated with perimenopausal bone mass, early postmenopausal bone loss and interact with hormone treatment. One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped, and haplotypes were determined. BMD was examined by dual X-ray absorptiometry. Women carrying the -1997T variant had lower BMD at all measured sites: lumbar spine BMD 1.030 ± 0.137 g/cm(2), 1.016 ± 0.147 g/cm(2) and 0.988 ± 0.124 g/cm(2) in women with the GG, GT and TT genotypes, respectively (p < 0.05) and total hip BMD 0.921 ± 0.116 g/cm(2), 0.904 ± 0.123 g/cm(2) and 0.887 ± 0.109 g/cm(2) in women with the GG, GT and TT genotypes, respectively (p = 0.01). The effect remained after 10 years although statistical significance was lost. Haplotype 3 (-1997T-1663ins + 1245G) was associated with lower bone mass and higher levels of bone turnover. Compared with haplotype 1, haplotype 3 carriers had lower BMD at the lumbar spine, femoral neck and total hip by 0.016 ± 0.007 g/cm(2), 0.015 ± 0.006 g/cm(2) and 0.017 ± 0.006 g/cm(2), respectively (p < 0.05-0.005). No association with postmenopausal changes in bone mass and fracture risk and no overall interaction with the effects of hormone therapy could be demonstrated for any of the polymorphisms in COLIA1. The -1997G/T polymorphism and haplotype 3 are significantly associated with perimenopausal bone mass, and these effects were sustained up to 10 years after menopause. No association between the -1663indelT or +1245G/T polymorphisms and peri- or postmenopausal bone mass could be demonstrated.

High bone mass as a marker for breast cancer risk.

Postmenopausal women in the highest quartile for metacarpal bone mass were found to have an increased risk of developing breast cancer, after adjusting for age and other variables known to influence breast cancer risk. Although the mechanisms responsible for this relationship have not been identified, postmenopausal bone mass may serve as an indicator of cumulative estrogen exposure.

LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women

Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exon 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-up period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06–2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02–2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures.

Association of oestrogen receptor α gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone

Background: The gene encoding oestrogen receptor α (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk. Objective: To investigate the relation between common polymorphisms...

Association between VDR &amp;lt;italic&amp;gt;Apa&amp;lt;/italic&amp;gt;I Polymorphism and Hip Bone Mineral Density Can Be Modified by Body Mass Index: A Study on Postmenopausal Chinese Women

Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR) gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD) variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age (P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However, the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI (P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.

CYP17 gene polymorphisms: prevalence and associations with hormone levels and related factors. a HuGE review.

The cytochrome P-450c17alpha (CYP17 ) gene, located on chromosome 10q24.3, encodes the enzyme cytochrome P-450c17alpha, which functions at key branch points in steroid hormone biosynthesis. Three polymorphisms have been described, but only the single base-pair change in the 5'-untranslated region (5'-UTR) has been investigated to any great extent. In single studies, the variant was associated with reduced messenger RNA level in ovarian cells but not with messenger RNA level in breast tissue. Homozygosity for the 5'-UTR variant is most common in East Asian (32%) and Japanese (22%) populations and is less common among White (mainly European and North American (14%)) and Black (mainly African-American (13%)) populations, but selection biases are likely to have affected these frequency estimates. Genotype appears to influence circulating estrogen levels in premenopausal women, while studies of relations with hormone levels in men have produced inconclusive results. However, relatively few studies have been conducted. Seven of 11 retrospective studies suggested a modest association between genotype and age at menarche. Random error in recall of age at menarche is likely to have attenuated this relation. Associations between genotype and postmenopausal estrogen use and bone mass have been observed in single studies. Further investigation of relations between genotype and hormone levels, exogenous hormone use, and markers of hormonal status may advance understanding of hormonally mediated diseases.

Inverse correlation between serum leptin concentration and vertebral bone density in postmenopausal women

Although the protective effect of obesity on bone mass has been ascribed to high body fat content ,this is still controversial. The present study of 215 postmenopausal Japanese women investigated whethercirculating leptin concentration was correlated with per cent fat mass or age-adjusted bone mineral density (Z-score). In this study population ,the mean circulating leptin concentration was 10.15 ±5.42 (range 1.7-29.6) ng/ml. Significant correlations were found between circulating leptin concentrations and per cent fat mass (r = 0.514 ,p < 0.0001) and Z-score (r = -0.516 ,p< 0.0001) ,confirming the existence of an inverse relationship between leptin concentration and postmenopausal bone density. By contrast ,no significant correlation was found between per cent abdominalfat mass and vertebral bone mineral density (r = -0.071). Serum leptin concentration reflects fat mass and postmenopausal bone mass in human subjects. Increased serum leptin levels might cause boneloss in postmenopausal Japanese women ,and our results do not support the hypothesis that leptin induces or mediates the bone-protective effects of obesity.

Vitamin D receptor gene polymorphisms, bone mineral density and bone turnover: FokI genotype is related to postmenopausal bone mass

The relationship between vitamin D receptor (VDR) intragenic polymorphisms FokI, BsmI, ApaI and TaqI and bone mineral density (BMD) or biochemical markers of bone remodeling were investigated in 114 Czech postmenopausal women, on the average 62.5±8.9 years of age. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in the VDR locus. Bone mineral density was measured at the lumbar spine and at the hip by dual-energy X-ray absorptiometry (DEXA, g/cm2). After adjusting for age and the body mass index (BMI), subjects with the ff genotype had 9.4 % lower BMD at the hip than those with the Ff genotype (p=0.0459, Tukey´s test). FF individuals had an intermediate BMD at the hip. A similar pattern of lower lumbar spine BMD was also found in ff individuals, but it did not reach statistical significance. There was no relationship between BsmI, ApaI and TaqI VDR polymorphisms and BMD at any skeletal site. Subjects with Aa (ApaI) genotypes had higher levels of propeptide of type I collagen (PICP) than homozygous AA (p=0.0459, Tukey´s test). In FokI, BsmI and TaqI restriction sites the biochemical markers of bone remodeling did not differ by genotype. In addition, no significant difference was observed in VDR genotypic distribution between osteoporotic women and non-osteoporotic controls in the study group. To conclude, the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident.

Masa ósea cortical y factores de riesgo para osteoporosis en mujeres postmenopáusicas en nuestro medio

To evaluate the relevance of the so called risk factors for osteoporosis among women. A total of 150 consecutive postmenopausal women who had been enrolled in the gynecology outpatient clinics of the Health Areas affiliated to the Alcalá de Henares University Hospital. Bone mass of these women was calculated as index of metacarpal cortical area/total area (CA/TA) (mm2), measured by radiogrammetry. With the ANOVA test, a late menarchial age and a shorter reproductive life induced a lower bone mass (p < 0.0005 and < 0.05, respectively); also, a history of bone fractures without previous relevant trauma (p < 0.05) was obtained. By correlational studies, there was a negative significance between CA/TA index and chronological age, menarchial age, menopausal age and number of fractures (r = -0.20 to -0.30; p < 0.05 to < 0.0001) and a positive significance with years of reproductive life (r = 0.17; p < 0.05). These values virtually remain unchanged when with partial correlation are weight adjusted, but with the multiple regression model, the CA/TA index is negatively significant only with menopause years (p < 0.005). Taking the average of the metacarpal CA/TA index as value, a sensitivity of 50% and an specificity of 78% were obtained to indicate fractures and a negative predictive value of 92%. These results indicate the greater importance of menarchial age, of reproductive life years and therefore of menopausal years, as determinants of postmenopausal bone mass and show a very acceptable specificity of the CA/TA index as predictive for bone fracture.

Postmenopausal weight status, body composition and body fat distribution in relation to parameters of menstrual and reproductive history

Objectives: In the present study the association between menstrual and reproductive history patterns and weight status, fat distribution and body composition during postmenopause was tested. Methods: In 106 healthy postmenopausal women ranging in age from 48 to 58 years ( x=53.7 year) the weight status was classified according to the recommendations of the WHO. Additionally body composition was estimated by dual energy X-ray absorptiometry and fat distribution was calculated using the fat distribution index. Weight status, body composition and fat distribution were correlated with self-reported parameters of menstrual and reproductive history (age at menarche, average cycle length, number of births, age at first and last birth, average pregnancy weight gain, age at menopause). Results: It was shown that number of births, age at first birth and pregnancy weight gain were related significantly to the postmenopausal weight status, body composition and fat distribution. Conclusion: An early first birth a low number of births and a high weight gain during pregnancies can be assumed as risk factors for overweight, a higher amount of adipose tissue, android fat patterning and therefore for the development of the metabolic syndrome during postmenopause. In contrast no adverse effect of menstrual and reproductive parameters on postmenopausal bone mass was found.

The individual age at menopause — An appropriate indicator of postmenopausal body composition?

The interaction between age at menopause and postmenopausal body composition development was tested with in 178 Viennese women aged 47 to 68 years (x=55.4 yr). Postmenopausal body composition was described using dual energy x-ray absorptiometry by absolute fat and lean mass and bone mineral content of the whole body, the arms, legs, the trunk and the head. Upper and lower amount of body fat, the fat percentages of the individual body compartments and the fat distribution index were calculated. Postmenopausal body fat and lean soft tissue mass and postmenopausal bone mineral content were significantly associated with the age at menopause. Women whose menopause occurred late showed the highest amount of body fat (31.2+/−7.7kg) and lean body mass (41.2+/−4.4 kg) postmenopausally, while women with an early menopause exhibited the lowest amount of body fat (27.5+/−8.9kg) and lean body mass (38.4+/−5.4 kg) during the postreproductive phase of life (p<0.05). Women whose menopause occurred later than 51 had a significant higher postmenopausal bone mass (2.26+/−0.9kg versus 2.09+/−0.3 kg; p<0.05). A late menopause was associated with a significantly higher value in fat mass, lean body mass and in bone mineral content. Therefore age at menopause may be assumed as an indicator for body fat and bone mineral content during postmenopause and postmenopausal fat distribution patterns.

Fracture rate, pre- and postmenopausal bone mass and early and late postmenopausal bone loss are not associated with vitamin D receptor genotype in a high-endemic area of osteoporosis.

To investigate a possible association between vitamin D receptor genotype and development of postmenopausal osteoporosis, a longitudinal study from 1977 to 1995 was carried out on women living in Oslo, Norway. One hundred and eighteen premenopausal women born in 1930 were included in a study of pre- and postmenopausal bone loss in 1977. In 1995, blood samples for vitamin D receptor genotyping were available in 72, 42 and 49 of the women eligible for the determination of premenopausal bone mineral content, early postmenopausal appendicular bone loss and late postmenopausal bone mineral content, bone loss and fractures, respectively. Bone mineral density was measured in the distal and proximal right forearm annually from 1977 to 1987, and in the lumbar spine, proximal femur, right forearm and total body, including ultrasound measurements of the right calcaneus, in 1993 and 1995. Non-spinal fractures were also recorded. The results were compared to the individual vitamin D receptor genotype and it was found that vitamin D receptor genotype was neither associated with non-spinal fractures, pre- and post-menopausal bone mass nor with early and late postmenopausal bone loss within the age of 65 years. In conclusion, premenopausal bone mass, postmenopausal bone loss and the subsequent risk of osteoporosis and fractures were not predicted by vitamin D receptor genotype in a high-endemic area of osteoporosis.

No associations between vitamin D receptor genotype and fracture rate, pre- and postmenopausal bone mass, and early and late postmenopausal bone loss in a high-endemic area of osteoporosis

No associations between vitamin D receptor genotype and fracture rate, pre- and postmenopausal bone mass, and early and late postmenopausal bone loss in a high-endemic area of osteoporosis

Genetic influence on bone turnover in postmenopausal twins.

Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.

Ipriflavone effect on prevention and treatment of postmenopausal bone mass loss. Relation to estrogen replacement therapy

Ipriflavone effect on prevention and treatment of postmenopausal bone mass loss. Relation to estrogen replacement therapy

Determinants of lumbar bone mineral density in normal weight, non-smoking women soon after menopause. A study using clinical data and quantitative computed tomography

Is there an influence of oral contraceptive use, parity and lactation on early postmenopausal bone mass? Is assessment of reproductive history, body weight in combination with biochemical markers of bone metabolism suitable to predict lumbar bone mass soon after menopause? A cross-sectional study in 94 healthy, normal weight, non-smoking women, 1-3 years after spontaneous menopause. Bone mineral density (BMD) of the lumbar spine was measured with single energy quantitative computed tomography. Multiple regression analysis showed that only total duration of lactation and alkaline phosphatase (AP) levels are independently related to trabecular BMD (P = 0.001 and P = 0.002 respectively). AP was also associated with cortical BMD (P = 0.003). Assessment of reproductive history, body mass index and biochemical markers of bone metabolism could only account for 17% of the variation of trabecular BMD observed in the study population. This study suggests that total duration of lactation rather than parity is associated with trabecular BMD of the spine. Clinical assessment of risk factors unsuccessfully predicts lumbar BMD in healthy, early postmenopausal women.

Age-related differences in total and regional bone mass: A cross-sectional study with DXA in 429 normal women

Total body bone mineral content (TBBMC), total body bone mineral density (TBBMD) and regional bone mineral content (BMC) and density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA) in 429 normal women aged 15-83 years, of whom 242 were premenopausal and 187 postmenopausal. The population was divided into 5-year age groups. In the premenopausal women no changes in TBBMC, TBBMD or regional BMC and BMD were observed with age, and TBBMC and TBBMD values correlated well with body weight (p < 0.001). Postmenopausal women showed an overall reduction in bone mass (p < 0.001), more marked at the axial level than peripherally (1.6% vs. 0.8%/year). The values of TBBMC and TBBMD correlated well with chronological age, time since the onset of menopause and body weight (p < 0.001). In these women age did not correlate with body weight, which suggests that postmenopausal bone mass loss depends more on chronological age and time since the onset of menopause than on other variables. The stability observed in bone mass values from ages 15-19 to menopause highlights the importance of stimulating the acquisition of an appropriate peak bone mass in women before adolescence begins.