Effect of misoprostol on bone mineral density in women with postmenopausal osteoporosis

OBJECTIVE: To evaluate the effect of misoprostol on bone mineral density in postmenopausal women. MATERIALS AND METHODS: The study was performed in a randomized controlled prospective manner in 90 women with menopause at Süleymaniye Maternity and Women's Diseases Teaching and Research Hospital between January and December 2003. Cases were divided into three groups each consisting of 30 women who were in menopause for at least 1 year and had t-scores less than -1 by dual energy X-ray densitometry (DEXA). Group I was treated with misoprostol and calcium, Group II received tibolone and calcium and Group III was given calcium only and considered as control group. In all patients, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle were measured by DEXA and t and z scores were calculated. RESULTS: All groups were similar demographically. Bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle in the group treated with misoprostol, increased by 5, 8.1 and 3.6%, respectively. In the tibolone group, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle increased by 8.3, 5.3 and 7.8%, respectively. There was not a significant difference in t and z-scores and bone mineral density measurements between misoprostol and tibolon groups. CONCLUSION: Misoprostol may be an alternative treatment for patients with osteopenia and osteoporosis who are not suitable for hormone replacement therapy.     

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.     

Effects of exercise practice on the maintenance of radius bone mineral density in postmenopausal women

The effect of exercise practice on the radius bone mineral density (BMD) was investigated on 480 women at the age of perimenopause and later. The BMD at the 1/3 distal site of the radius on a non-dominant hand was measured using the Dual Energy X-ray Absorptiometry method. The subjects were divided into group E with regular exercising and group C without regular exercising. The difference of mean radius BMD values was not statistically significant between groups E and C. Each of the groups E and C was further classified into a perimenopause group and groups with stratified postmenopausal years (postmenopausal years less than 5, less than 10 and more than 10). Then, the mean radius BMD value of the perimenopause subgroup was taken as 100% for each of the groups E and C, and the relative radius BMD values of subgroups were compared between groups E and C. The relative BMD values for the subgroup of postmenopausal years more than 10 were higher in E group than those in C group, while no difference was observed in below postmenopausal 10 years between the two groups. To clarify the BMD difference among exercise events, group E was further divided into the following three subgroups: the subgroup practising events which give high-impact to arm (HI group), such as tennis, ping-pong, golf and volleyball, the subgroup practising swimming (SW group), and the subgroup practising events which give low-impact to arm (LI group), such as walking, running, aerobic dance and light gymnastics. No significant differences were observed in BMD values among the above sports event-stratified subgroups when postmenopausal years were less than 10 years, but the relative BMD values for the subgroup of postmenopausal years more than 10 were higher in HI and LI group than those in control group. These results suggest the possibility that exercise practice suppresses a postmenopausal decline in bone density for preventing osteoporosis from developing.     

Effects of physical training on bone mineral density and bone metabolism

The purpose of this study was to examine the influences of long-term walking training and walking and jumping training on bone mineral density (BMD) and bone metabolism. Data from 28 healthy premenopausal women was assessed. The subjects were divided into the walking group (WG; 17 women mean+/-SE age 35+/-2 years), and the walking and jumping group (WJG; 11 women mean+/-SE age 39+/-1 years). BMD was measured in the lumbar spine and proximal femur using dual energy X-ray absorptiometry (DXA). As markers of bone metabolism, this study was to measure bone formation markers, bone-alkaline phosphatase (B-ALP: measured by enzyme immunoassay/EIA) and osteocalcin (BGP: by radioimmunoassay/RI) as well as bone resorption markers, parathyroid hormone (PTH: measured by/RI) and type I collagen cross-linked N-telopeptides (NTx: by EIA). Despite the significant decrease in body weight (p<0.05), no corresponding decrease in BMD was observed. Moreover, no significant difference in bone markers BGP, PTH, and NTx was observed. B-ALP was significantly increased (p<0.05) after one year, and the rate of this increase was greater in the WJG than in the WG. It is thus concluded that walking training for one year is beneficial for the promotion of bone formation, and that jumping stimulus maintain BMD effectively.     

大豆异黄酮对去卵巢大鼠骨密度及骨代谢影响的实验研究

目的 探讨大豆异黄酮对去卵巢大鼠骨丢失的防治作用及其作用机理。方法 选用卵巢切除大鼠所诱发的骨质疏松模型,给与大豆异黄酮治疗。三个月后测定大鼠骨密度及骨代谢相关生化指标。结果 大豆异黄酮可提高卵巢切除大鼠的骨密度及血清雌激素水平,降低尿钙（Ca),尿磷（P）及尿羟脯氨酸（HOP）的排泄,同时降低血清总碱性磷酸酶（ALP）,骨碱性磷酸酶（BALP）,及抗酒石酸酸性磷酸酶（TRACP）的活性,还可使血清骨钙素（BGP）的浓度降低,促使卵巢切除大鼠子宫的相对重量增加,其作用与剂量相关。结论 小剂量大豆异黄酮有类似雌激素样作用,可有效防治卵巢切除大鼠的骨量丢失,其作用机制可能是通过降低骨转换率实现的。     

Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain.

OBJECTIVES--To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. DESIGN--Cross sectional twin study. SETTING--Twin population based in Britain. SUBJECTS--95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. MAIN OUTCOME MEASURES--Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. RESULTS--At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. CONCLUSIONS--The findings that in postmenopausal women in Britain bone density-particularly at the hip and spine-is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis.     

Increased thyroidal T4/T3 ratio in nodular and paranodular tissues of nontoxic goiter following suppressive treatment with thyroid hormones

The effect of suppressive treatment with thyroid hormones on thyroidal iodothyronines and T4/T3 ratio in nodular and paranodular tissues was investigated in 12 patients with nontoxic goiter. Results were compared to those from 11 nontreated patients. Continuous thyroid hormone administration produced a significant increase in thyroidal T4 and T4/T3 ratio in nodular tissues while T3 remained unchanged. In paranodular tissues a significant rise of T4/T3 ratio, an insignificant increase in T4 and a decrease in T3 were observed following the administration of thyroid hormones. The results are very similar to those obtained in paranodular tissue of autonomously functioning thyroid nodule, and are probably the consequence of suppressed TSH secretion, as TSH predominantly stimulates the synthesis of T3 and/or thyroidal T4 monodeiodination.     

The effects of weight loss on relative bone mineral density in premenopausal women

Objective:

This study compared BMD relative to body weight following a ～6‐month weight loss program and a 1‐year weight maintenance phase in premenopausal women and determined whether African American (AA) and European‐American (EA) women's BMD respond similarly during weight loss.

Design and Methods:

Premenopausal women (n = 115, 34 ± 5 years) were evaluated in an overweight state (BMI between 27 and 30 kg/m²), following an 800 kcal/day diet/exercise program designed to reduce BMI<25 kg/m², and 1‐year following weight loss.

Results:

BMD relative to body weight (Z‐scores) increased after weight loss, but decreased during the 1‐year weight maintenance phase. All 1‐year follow‐up BMD Z‐scores were increased (except L1) compared to baseline measurements (P < 0.05). These sites included the hip neck (+0.088, P = 0.014), total hip (+0.099, P = 0.001), L2 (+0.127, P = 0.013), L3 (+0.135, P = 0.014), and L4 (+0.199, P = 0.002). AAs had significantly higher absolute BMD at all sites (P < 0.05) compared to EAs, but no time by race interactions were evident during weight loss (except in L3).

Conclusion:

These results may indicate that weight loss is safe with regard to bone health for overweight premenopausal women.     

Effect of low-repetition jump training on bone mineral density in young women.

The hypothesis of the present study was that low-repetition and high-impact training of 10 maximum vertical jumps/day, 3 times/wk would be effective for improving bone mineral density (BMD) in ordinary young women. Thirty-six female college students, with mean age, height, and weight of 20.7+/-0.7 yr, 158.9+/-4.6 cm, and 50.4+/-5.5 kg, respectively, were randomly divided into two groups: jump training and a control group. After the 6 mo of maximum vertical jumping exercise intervention, BMD in the femoral neck region significantly increased in the jump group from the baseline (0.984+/-0.081 vs. 1.010+/-0.080 mg/cm2; P<0.01), although there was no significant change in the control group (0.985+/-0.0143 vs. 0.974+/-0.134 mg/cm2). And also lumbar spine (L2-4) BMD significantly increased in the jump training group from the baseline (0.991+/-0.115 vs. 1.015+/-0.113 mg/cm2; P<0.01), whereas no significant change was observed in the control group (1.007+/-0.113 vs. 1.013+/-0.110 mg/cm2). No significant interactions were observed at other measurement sites, Ward's triangle, greater trochanter, and total hip BMD. Calcium intakes and accelometry-determined physical daily activity showed no significant difference between the two groups. From the results of the present study, low-repetition and high-impact jumps enhanced BMD at the specific bone sites in young women who had almost reached the age of peak bone mass.     

Low mineral density of a weight-bearing bone among adult women in a high fertility population

Evolutionary theories of aging posit that greater reproductive effort causes somatic decline given a fundamental trade-off between investing energy in reproduction and repair. Few studies in high fertility human populations support this hypothesis, and problems of phenotypic correlation can obscure the expected trade-off between reproduction and somatic condition. This cross-sectional study investigates whether greater reproductive effort is associated with reduced calcaneal bone mineral density (BMD) among female Tsimane forager-farmers of lowland Bolivia. We also investigate whether female Tsimane BMD values are lower than sex- and age-matched US reference values, despite the fact that Tsimane engage in higher physical activity levels that can increase mechanical loading. To measure calcaneal BMD, quantitative ultrasonography was performed on 130 women (mean ± SD age = 36.6 ± 15.7, range = 15–75) that were recruited regardless of past or current reproductive status. Anthropometric and demographic data were collected during routine medical exams. As predicted, higher parity, short inter-birth interval, and earlier age at first birth are associated with reduced BMD among Tsimane women after adjusting for potential confounders. Population-level differences are apparent prior to the onset of reproduction, and age-related decline in BMD is greater among Tsimane compared with American women. Greater cumulative reproductive burden may lower calcaneal BMD individually and jointly with other lifestyle and heritable factors. Fitness impacts of kin transfers in adulthood may determine the value of investments in bone remodeling, and thus affect selection on age-profiles of bone mineral loss. Am J Phys Anthropol 156:637–648, 2015. © 2014 Wiley Periodicals, Inc.     

Association of interleukin 10 haplotype with low bone mineral density in Korean postmenopausal women

Osteoporosis is a disease characterized by exaggerated loss of bone mass, with as much as 50 to 85% of the variation in bone mineral density (BMD) commonly accepted as being genetically determined. Although intensive studies have attempted to elucidate the genetic effects of polymorphisms on BMD and/or osteoporosis in several genes, the genes involved are still largely unknown. The possible associations of genetic variants in five-candidate genes (IL10, CCR3, MCP1, MCP2 and GC) with spinal BMD were investigated in Korean postmenopausal women (n = 370). Fourteen SNPs in five candidate genes were genotyped, and the haplotypes of each gene constructed. The associations of adjusted spinal BMD by age, year since menopause (YSM) and body mass index (BMI), with genetic polymorphisms, were analyzed using multiple regression models. Genetic association analysis of Korean postmenopausal women revealed that IL10 -592A > C and/or IL10 ht2 were associated with decreased bone mass, whereas no significant associations were observed with all polymorphisms in other genes. The levels of spinal BMD in individuals bearing the IL10 -592CC genotype were lower (0.78 +/- 0.16) than those in others (0.85 +/- 0.17) (P = 0.02), and the BMD of IL10 ht2 bearing individuals were also lower (0.82 +/- 0.15) than those in others (0.85 +/- 0.17) (P = 0.04). Our results suggest that variants of IL10 might play a role in the decreased BMD, although additional study might need to be followed-up in a more powerful cohort.     

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.     

Zinc status of women with low bone mineral density who receive calcium supplements

We evaluated whether a daily high-dose calcium supplement perturbs the zinc status in 23 postmenopausal women (mean age: 63yr) with low bone mineral density. Plasma and erythrocyte zinc concentrations, plasma bone-specific alkaline phosphatase (BSAP) and 5′-nucleotidase activities, and urinary zinc and calcium excretion were determined first at the end of 4 wk of daily oral calcium (1200 mg) and were measured again at the end of the subsequent 4 wk of daily cosupplementation with calcium (1200 mg) and zinc (30 mg). Mean plasma and erythrocyte zinc concentrations after 4 wk of calcium alone were not significantly different from concentrations after cosupplementation of calcium and zinc. Mean plasma BSAP activities before cosupplementation with zinc was significantly higher than that after zinc (p<0.02), whereas plasma 5′-nucleotidase activities were not affected by zinc supplementation. Urinary zinc excretion slightly, but significantly, increased after the supplementation of zinc (p<0.05), whereas calcium excretion remained similar. Our data indicate that a 4-wk zinc supplementation did not significantly improve zinc status. Although limited by the small sample size and short study duration, our data suggest that a daily calcium dose of 1200 mg had no effect on the zinc status of our subjects.     

Influence of bone mineral density in circulating adipokines among postmenopausal Arab women

Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall −0.34, p < 0.01; low BMD group −0.34, p < 0.01). In multiple regression, adiponectin (−0.29 ± 0.06, p < 0.00) and resistin (−0.08 ± 0.04, p < 0.05) were inversely significant with BMD overall, but after stratification the significance was lost for resistin (−0.05 ± 0.04, p < 0.224) whereas adiponectin remained (−0.22 ± 0.07, p < 0.02) in low-BMD subjects. Adipsin, leptin and lipocalin-2 showed no significant associations. Findings of the present study revealed that only adiponectin showed a significantly strong inverse association with low BMD, suggesting that insulin sensitivity may influence bone health in Arab postmenopausal women.     

Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism

AIM: To investigate whether nasal salmon calcitonin (CT; 200 U/day) given in addition to calcium helps to restore the bone mass after parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT). METHODS: Twenty patients with PHPT were enrolled after successful PTX and received 1 g calcium per os daily for 1 year. They were randomly assigned either to nasal CT (CT group) or to no treatment. The bone mass was measured using dual-energy X-ray absorptiometry at multiple sites. RESULTS: Eight patients in each group completed the study. After 12 months, the bone mass increased significantly at whole-body level and at lumbar spine in both groups, increased at hip and epiphyses of tibia or radius in the CT group only, and did not change at diaphyses of tibia and radius in either group. CONCLUSIONS: Bone mass increases after PTX for PHPT in patients receiving oral calcium. CT may help to restore the bone mass at sites of the appendicular skeleton, where trabecular bone predominates.     

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.     

Automated determination of bone age and bone mineral density in patients with juvenile idiopathic arthritis: a feasibility study

Introduction

Chronic inflammation combined with glucocorticoid treatment and immobilization puts juvenile idiopathic arthritis (JIA) patients at risk of impaired growth and reduced bone mineral density (BMD). Conventional methods for evaluating bone age and BMD are time-consuming or come with additional costs and radiation exposure. In addition, an automated measurement of bone age and BMD is likely to be more consistent than visual evaluation. In this study, we aimed to evaluate the feasibility of an automated method for determination of bone age and (cortical) bone mineral density (cBMD) in severely affected JIA patients. A secondary objective was to describe bone age and cBMD in this specific JIA population eligible for biologic treatment.

Methods

In total, 69 patients with standard hand radiographs at the start of etanercept treatment and of calendar age within the reliability ranges (2.5 to 17 years for boys and 2 to 15 years for girls) were extracted from the Dutch Arthritis and Biologicals in Children register. Radiographs were analyzed using the BoneXpert method, thus automatically determining bone age and cBMD expressed as bone health index (BHI). Agreement between measurements of the left- and right-hand radiographs and a repeated measurement of the left hand were assessed with the intraclass correlation coefficient (ICC). Regression analysis was used to identify variables associated with Z-scores of bone age and BHI.

Results

The BoneXpert method was reliable in the evaluation of radiographs of 67 patients (radiographs of 2 patients were rejected because of poor image quality). Agreement between left- and right-hand radiographs (ICC = 0.838 to 0.996) and repeated measurements (ICC = 0.999 to 1.000) was good. Mean Z-scores of bone age (−0.36, P = 0.051) and BHI (−0.85, P < 0.001) were lower compared to the healthy population. Glucocorticoid use was associated with delayed bone age (0.79 standard deviation (SD), P = 0.028), and male gender was associated with a lower Z-score of BHI (0.65 SD, P = 0.021).

Conclusions

BoneXpert is an easy-to-use method for assessing bone age and cBMD in patients with JIA, provided that radiographs are of reasonable quality and patients’ bone age lies within the age ranges of the program. The population investigated had delayed bone maturation and lower cBMD than healthy children.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0424-1) contains supplementary material, which is available to authorized users.