Moderate physical activity is associated with higher bone mineral density in postmenopausal women

OBJECTIVES: To determine the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and bone mineral density (BMD) in postmenopausal women. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: Twenty sedentary women, 20 active nonathletic women, and 23 endurance-trained athletes, all of whom were postmenopausal, with half of each group on and half not on HRT. MEASUREMENTS: BMD and body composition determined by dual energy x-ray absorptiometry, maximal oxygen consumption (VO2max), dietary history by questionnaire, and vitamin D receptor (VDR) genotyping on deoxyribonucleic acid. RESULTS: Body weight was higher in the active nonathletic than in the sedentary and athletic women. Body fat was lower and VO2max higher in the athletic women than in the sedentary and the active nonathletic women. Physical activity level was significantly associated with BMD in three of the five measurements taken (L1-L4 lumbar spine, trochanter, total body; all P < .05). These differences were also generally significant after adjusting for body weight. The association between physical activity status and BMD at the neck of the femur and Ward's triangle bordered on significance (P = .07-.09). At most sites, the active nonathletic women had higher BMD than did the sedentary and athletic women. HRT was significantly associated only with total body BMD (P < .05). The groups were similar in terms of dietary habits (protein, calcium, sodium, phosphorus intake); VDR genotypes; and family, smoking, and nutritional histories. CONCLUSION: Given the similarity of the groups with respect to other factors that affect BMD, it appears that prolonged low-to-moderate-intensity physical activity, but not the same number of years of higher-intensity training for competitive events, was independently associated with higher BMD.     

Relation of low bone mineral density and carotid atherosclerosis in postmenopausal women

Due to the lack of convincing data about the association between atherosclerosis and osteoporosis, we evaluated the association between carotid atherosclerosis and bone mineral density in a sample of apparently healthy postmenopausal women who underwent health-screening in our hospital. We also evaluated a bone turnover marker, osteocalcin; we divided the population into 2 groups according to osteocalcin levels. We found a high prevalence of carotid atherosclerosis in subjects with high osteocalcin levels and low bone mineral density.     

Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women

OBJECTIVE: Although total fat body mass (FM) is considered to be one of the major determinants of bone mass, the mechanism by which FM and bone mass are positively correlated remains unclear. Leptin, the product of the obese (ob) gene, is secreted from adipocytes and its plasma levels are known to be positively correlated with %fat (FM divided by total body weight). There is recent evidence suggesting that leptin directly stimulates osteoblastic differentiation. Thus it is possible that the anabolic action of this hormone on bone may participate in the positive correlation between FM and bone mass. In this study, we analysed the relationships between either plasma leptin levels or %fat vs. bone mineral density (BMD) values as well as the presence of vertebral compression fractures, and evaluated whether or not plasma leptin levels were associated with BMD or bone fragility in a manner independent of FM. PATIENTS: One hundred and thirty-nine postmenopausal women (age 48-78 years, mean 62.5), who visited our outpatient clinic for the evaluation of osteoporosis. DESIGN AND MEASUREMENTS: Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral neck and whole body. Distal one-third of radius BMD was measured by single photon absorptiometry (SPA). Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs. RESULTS: Although neither plasma leptin levels nor %fat correlated with age, there was a significant positive correlation between plasma leptin levels and %fat (r = 0.563, P < 0.001). Plasma leptin levels were significantly and positively correlated with BMD values at all skeleton sites measured, and multiple regression analysis revealed that this positive relationship was still observed with BMD values of the femoral neck and of the whole body, even after %fat and age were taken into account. Moreover, plasma leptin levels but not %fat were significantly lower in women with vertebral fractures than in those without fractures. When multiple logistic regression analysis was performed with either plasma leptin value or %fat employed as independent variables, plasma leptin values but not %fat were selected as an index affecting the presence of vertebral fractures. CONCLUSION: Our study showed that plasma leptin levels but not %fat are associated with BMD and the presence of vertebral fractures in postmenopausal women, suggesting that circulating leptin might play a physiological role in maintaining bone mass as well as better bone quality.     

Apolipoprotein E 4 allele is associated with low bone density in postmenopausal women

Apolipoprotein E (Apo E) genotypes have been associated with a number of involutional disorders. Recently some studies have examined whether the Apo E 4 allele might play a role in the pathophysiology of postmenopausal osteoporosis. However, association analysis between Apo E genotypes, BMD, bone loss or fracture risk have not brought universal findings. The aim of this study was, therefore, to determine the relationship between the presence or absence of Apo E 4 allele and BMD in postmenopausal women of Caucasian origin. We studied 113 women, age 62.5 +/- 8.9 yr, who underwent measurement of hip and spine BMD by dual-energy absorptiometry (DXA, g/cm2). Apo E genotypes were assessed by PCR amplification and by restriction typing with Cfol enzyme. The Apo E allele frequencies in the study population were as follows: E2 0.084, E3 0.845, E4 0.071. Because the Apo E 4 allele was associated with osteoporosis in previous studies, the probands were dichotomized by the presence or absence of Apo E 4 allele. After adjustment for BMI and years since menopause BMD at the lumbar spine varied significantly by Apo E 4 status. Women with Apo E 4 allele had significantly lower BMD at the lumbar spine than women with no Apo E 4 allele (p<0.003, ANCOVA). In contrast, there were no significant differences in BMD at the hip comparing women with or without the Apo E 4 allele. To conclude, these data may support the importance of Apo E 4 allele in determining postmenopausal spine bone mass.     

Low TSH levels are not associated with osteoporosis in childhood

INTRODUCTION: A recent study on TSH receptor (TSHR) null mice suggested that skeletal loss occurring in hyperthyroidism is caused by the low TSH rather than high thyroid hormone levels. The aim of this study was to examine whether low TSH results in osteoporosis in the human. SUBJECTS AND METHODS: We determined bone mineral density (BMD) and markers of bone metabolism in two male siblings aged 9.8 and 6.8 years with isolated TSH deficiency, due to a mutation of the TSH beta-subunit gene. BMD was measured in the lumbar spine (L1-L4) by dual-energy X-ray absorptiometry. Laboratory investigation included the determination of serum calcium, phosphate, 25-hydroxy-vitamin D, parathyroid hormone concentrations, and urine calcium (Ca)/creatinine (Cr) ratio. Osteoblast activity was measured by serum bone alkaline phosphatase and osteocalcin levels, and osteoclast activity by urine cross-linked amino-terminal, carboxy-terminal telopeptides of type I collagen and deoxypyridinoline concentrations. RESULTS: BMD of both patients was within the normal range for age and sex; z-scores were -0.55 and -0.23 for patients 1 and 2 respectively. Serum calcium, phosphate, urine Ca/Cr ratio, and specific markers of bone metabolism were also within normal range. CONCLUSION: In childhood, chronic extremely low TSH levels, in the face of normal thyroid hormone levels, are not related to bone loss.     

Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women

Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.     

Calcium-sensing receptor gene polymorphism is not associated with bone mineral density in Italian postmenopausal women

OBJECTIVE: Calcium-sensing receptor (CaR) is a candidate gene for osteoporosis susceptibility. Several CaR polymorphisms have been identified and an association between the A986S genotype and serum calcium levels has been found in Canadian postmenopausal women. We investigated whether the presence of 986S allele was associated with bone mineral density (BMD) and osteoporotic fractures. DESIGN: The study group consisted of 164 Italian postmenopausal women without fragility fracture (Fx(-)) and 55 women with fracture (Fx(+)). METHODS: A fragment of exon 7 of CaR gene containing three polymorphisms (A986S, R990G and Q1011E) was amplified by PCR and sequenced. Anthropometric characteristics and BMD were evaluated. RESULTS: The A986S polymorphism was the most commonly observed (27.9%), whereas the other two CaR polymorphisms, R990G and Q1011E, occurred in a minority of cases (8.8 and 5.5% respectively). There was no significant difference in the frequency distribution of any CaR allele between Fx(-) and Fx(+) patients. Body mass index was found to predict BMD at the lumbar spine and femoral neck. The A986S polymorphism and Years since menopause were not independent predictors of BMD at any site. As far as fracture occurrence, there was no statistically significant difference in the prevalence of fractures between women carrying or not carrying the 986S allele. CONCLUSIONS: Our data do not support a role of A986S CaR polymorphism in BMD and in the prevalence of fragility fractures in Italian postmenopausal women.     

Anemia as a risk factor for low bone mineral density in postmenopausal Turkish women

BackgroundWe investigated the association of bone mineral density (BMD) by detected dual-energy X-ray absorptiometric (DXA) method and hemoglobin (Hb) levels in a large sample.MethodsThe current study enrolled 371 postmenopausal women (82 anemic patients), who were screened for osteopenia or osteoporosis by DXA. Patients with osteopenia or osteoporosis (T score < ? 1.0 SD) were grouped as having low bone mass (LBM).ResultsAnemic patients were older and had significantly higher duration of menopause. When compared with subjects with normal Hb, anemic patients had significant lower femur t score, femur BMD, femur Z score, spinal t score, spinal BMD and spinal Z score (p < 0.001). Additionally, the ratio of subjects with LBM in the femur and spine were significantly high in anemic patients (p < 0.002, p < 0.002, respectively). There were significant correlations between Hb values and femur t score, femur BMD, spine t score, and spine BMD values of the study population in bivariate correlation analysis (r = 0.150, p = 0.004, r = 0.148, p = 0.004, r = 0.160, p = 0.002, r = 0.164, p = 0.001, respectively). Furthermore, presence of anemia was found to be an independent predictor of LBM for spine [OR: 2.483 (95% CI: 1.309–4.712), p < 0.005] in logistic regression analysis. Additionally, number of anemic patients was significantly high in low femur and spine BMD groups (56 vs. 26; p = 0.01, 66 vs. 16; p = 0.002, respectively).ConclusionWe have found that the presence of anemia was as an independent predictor of LBM for spine after adjusting for body mass index and other confounders in postmenopausal Turkish women.     

Predicting bone mineral density of postmenopausal healthy and cirrhotic Italian women using anthropometric variables

Background. Chronic liver diseases, including cirrhosis of the liver, have been shown to cause bone osteometabolic disease giving rise to osteoporosis and osteomalacia.

Aims. To develop mathematical prediction equations for the lumbar-spine, pelvis and total bone mineral density based on the osteoporosis risk factors age and body mass index in cirrhotic and healthy postmenopausal women.

Patients. Twenty-seven postmenopausal women with liver cirrhosis (Child–Pugh class A) and well-preserved liver function (Late postmenopausal cirrhotic), 27 women matched for age and body mass index (Late postmenopausal healthy) and 27 younger women matched only for body mass index (Early postmenopausal healthy).

Methods. Segmental and total fat mass, lean body mass and bone mineral density were measured for all participant women using dual X-ray absorptiometry.

Results. Segmental and total fat mass and bone mineral density were significantly lower for Late postmenopausal cirrhotic women as compared with Late and Early postmenopausal healthy women. Segmental and total lean body mass were comparable among the three study groups.

Conclusions. The mathematical equations based on the variables age and body mass index were capable of predicting lumbar-spine bone mineral density, pelvis bone mineral density and total bone mineral density for the three groups of postmenopausal women with the lowest standard error of estimation and root mean square residuals of predictions for equations describing the Late postmenopausal healthy group.     

Genetic variant in the aquaporin 9 gene is associated with bone mineral density in postmenopausal women

This study investigated whether single nucleotide polymorphisms (SNP) in the aquaporin 9 (AQP9) gene is associated with bone mineral density (BMD) in Thai postmenopausal women, after an initial genome-wide screening using high-throughput SNP genotyping in pooled DNA samples. Subjects consisted of 516 postmenopausal women aged 50 or more. High-throughput SNP screening was performed by comparing the estimated allele frequency derived from hybridization signal intensities of pooled DNA samples on the Affymetrix 500 K SNP genotyping chip set. The SNP was then genotyped for each subject individually. Data were expressed as mean ± SEM. Pooled DNA SNP screening revealed the allele frequency of an intronic A/T SNP rs2414539 in the AQP9 gene as being different between subjects with femoral neck BMD in tertiles 1 and 3. Individual genotyping in all subjects revealed that femoral neck BMD in subjects with TT, TA, and AA genotypes were 0.79 ± 0.06 (n = 3), 0.75 ± 0.01 (n = 98), and 0.71 ± 0.01 g/cm(2) (n = 415), respectively. The presence of the T allele in rs2414539 was associated with femoral neck BMD (r = 0.11, P < 0.05) but not with lumbar spine BMD. The relationship was still significant after controlling for body weight and age (P < 0.05). Genetic variation in the AQP9 gene is associated with femoral neck BMD in postmenopausal women, and may represent one of the susceptibility genes for phenotypes related to bone mass.     

Low grip strength is associated with bone mineral density and vertebral fracture in women

OBJECTIVES: Grip strength has been reported to be associated with bone mass locally at the forearm and also at distant skeletal sites, including the spine and hip. Less is known about the association between low grip strength and risk of vertebral fracture. The aim of this study was to examine the association between low grip strength, bone mineral density at the hip and spine, and vertebral fracture in middle-aged and elderly European men and women. METHODS: Men and women aged 50 yr and over were recruited for participation in a screening survey of vertebral osteoporosis across Europe. Subjects who agreed to take part had an interviewer-administered questionnaire and lateral spinal radiographs performed. Subjects were assessed also for grip strength using a handgrip dynamometer (range 0-300 mmHg). A subsample of those recruited had bone mineral density measurements performed at the spine and femoral neck. Subjects had repeat lateral spine radiographs performed a mean of 3.8 yr following the baseline survey. Linear regression analysis was used to determine the association between low grip strength and bone mineral density at the hip and spine. Logistic regression was used to determine the association between grip strength and both prevalent and incident vertebral fracture. RESULTS: One thousand two hundred and sixty-five men and 1380 women with data concerning grip strength and bone mineral density were included in the analysis. In women, after age adjustment, compared with those with 'normal' grip, those with 'impaired' (231-299 mmHg) and low grip (<231 mmHg) had significantly lower bone mass at the spine and femoral neck. In men, those with low grip strength had a lower BMD at the spine and hip than those in the normal group. However, because of the small numbers with submaximal grip strength, the confidence intervals around all estimates included zero. Adjustment for body size and levels of physical activity had little effect on the results. In addition, among women, after adjustment for age, body mass index and physical activity levels, compared with those with normal grip, those with low grip strength had an increased risk of developing incident vertebral fracture (odds ratio = 2.67; 95% confidence interval 1.13, 6.30). Further adjustment for spine bone density had little influence on the association (odds ratio = 2.60). CONCLUSIONS: In women, low grip strength is associated with low bone mineral density at both the spine and hip and an increased risk of incident vertebral fracture. These associations cannot be explained by differences in body size or lifestyle.     

体重、体重指数对健康绝经后妇女骨密度的影响

目的探讨体重和体重指数（BMI）对健康绝经后妇女骨密度（BMD）的影响。方法采用双能X线骨密度仪测量591例健康绝经后女性不同部位的BMD，按BMI不同分为低体重组、正常体重组和肥胖组进行分析。结果各部位的BMD随BMI的增加而增高（P〈0．01）。BMD随年龄的增长而降低（P〈0．01）。肥胖组各部位BMD均比正常体重组和低体重组高（P〈0．05或P〈0．01）。年龄和体重是决定BMD变异的主要因素，年龄与BMD呈负相关，体重与BMD呈正相关，绝经年龄与腰椎正位BMD呈正相关；BMI与BMD无相关性。结论体重是影响绝经后妇女BMD的重要因素。对低体重的绝经后妇女定期监测BMD，有助于早期干预。     

Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women

BACKGROUND: Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial, but the presence of osteoporosis is regarded as an indication for parathyroidectomy. Hormone replacement therapy (HRT) is a possible alternative therapy in osteopenic postmenopausal women with the disorder, and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy. Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism. METHODS: We report the results of the extension from 2 to 4 years of a randomized, placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism. Of 23 postmenopausal women with primary hyperparathyroidism, 11 received active HRT with conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 5 mg/d, and 12 received placebo. Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects. None of the 23 patients withdrew during the extension period. RESULTS: Changes in bone mineral density were more positive in those taking HRT than placebo, with the between-group differences at 4 years being 4.6% in the total body, 7.5% in the lumbar spine, 7.4% in the femoral neck, 8.2% in the femoral trochanter, 6.8% in the legs, and 7.0% in the forearm (P<.01). At skeletal sites composed predominantly of cortical bone, there was a progressive divergence of the 2 groups. Biochemical markers of bone turnover remained lower throughout the study in women taking HRT. When rates of bone loss were compared between the placebo group and healthy women of comparable age, bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism, but only in the total body and its legs subregion was this difference significant. CONCLUSIONS: Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery. Bone loss seems to be accelerated in untreated primary hyperparathyroidism.     

The use of moexipril in postmenopausal women with hypertension and associated changes of bone mineral density

Moexipril was given to 35 postmenopausal women with mild and moderate hypertension, menopausal syndrome and decreased bone mineral density. Blood pressure (BP) was measured before and in 1, 3, 6, and 12 months, while ultrasonic bone densitometry was carried out before and in 12 months of moexipril use. Significant lowering of systolic and diastolic BP, reduction of severity of climacteric syndrome occurred after 1, 3 and 6 months of moexipril use, respectively. After 12 months parameters of bone densitometry in moexipril treated women became better than in control group (p<0.01). Treatment was also associated with significant improvement of quality of life, diminished reactive anxiety and depression.     

Lack of relationships between cumulative methylprednisolone dose and bone mineral density in healthy men and postmenopausal women with chronic low back pain

 The medical use of glucocorticoids (GCs) is related to low bone mineral density (BMD). In this study we tested the hypothesis that the cumulative dose of GC is not related to BMD outcome. The study was cross-sectional in design and included healthy individuals with chronic low back pain resistant to conventional treatments. In two steroid-naive subjects cortisol and methylprednisolone (MP) concentrations were serially assessed after a single MP depot injection (160 mg epidurally). Furthermore, in 14 men and 14 postmenopausal women, previously treated with multiple epidural MP depots, endocrine parameters were analysed in relation to BMD outcomes. The minimal cumulative MP dose received by all 28 subjects was 3 g. In the two steroid-naive subjects, cortisol concentrations were completely suppressed for at least 6 days and partly recovered over the course of 30 days. During this period, MP concentrations remained detectable in plasma. In the 28 subjects, the cumulative MP dose received was 7.76±4.23 g in the men and 8.50±3.13 g in the women (mean±1SD). None of the men had osteoporosis, but osteopenia was prevalent in 78.5% according to WHO criteria extrapolated to men. Half of the women had osteoporosis and half of them had osteopenia. The body mass index (BMI) and endogenous oestradiol levels of the men were not related to BMD outcomes. Univariate linear relationships in women were found between BMI and spinal (r 0.62; P=0.02) and total hip BMD (r 0.61; P=0.03), but not femoral neck BMD. In women, relationships were also found between the total and, for protein binding-corrected oestradiol levels, and spinal BMD (r 0.70; P=0.01 and r 0.72; P=0.01, respectively) and total hip BMD (r 0.53; P=0.08 and r 0.56; P=0.05, respectively). No significance was observed between endogenous oestradiol levels and the BMD of the femoral neck. The administration of a single MP depot injection (160 mg) resembled a systemic low peak dose GC exposure. The administration of multiple MP depots in men and women with chronic low back pain revealed no relationship between cumulative GC dose and BMD. These findings support the hypothesis of a non-existent relationship between cumulative GC dose and BMD outcomes in healthy men and women with a prior GC administration of at least 3 g. Received: 18 February 2002 / Accepted: 14 June 2002 Acknowledgements We are indebted to Dr Oscar L.H. van Hemel for advice during the performance of the study and to Ineke Bosman for excellent laboratory support.