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

<p><b>Purpose:</b> Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.</p> <p><b>Methods:</b> Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.</p> <p><b>Results:</b> 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.</p> <p><b>Conclusions:</b> Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.</p&gt

Regional variation and determinants of vitamin D status in sunshine-abundant Thailand

<p>Abstract</p> <p>Background</p> <p>Vitamin D insufficiency is highly prevalent. Most of the studies concerning vitamin D status were generated from countries situated at temperate latitudes. It is less clear what the extent of vitamin D insufficiency is in countries situated in the tropics and how geographical regions within country would affect vitamin D status. In the present study, we investigated vitamin D status in Thais according to geographical regions and other risk factors.</p> <p>Methods</p> <p>Subjects consisted of 2,641 adults, aged 15 - 98 years, randomly selected from the Thai 4th National Health Examination Survey (2008-9) cohort. Serum 25 hydroxyvitamin D were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE.</p> <p>Results</p> <p>Subjects residing in Bangkok, the capital city of Thailand, had lower 25(OH)D levels than other parts of the country (Bangkok, central, northern, northeastern and southern regions: 64.8 ± 0.7, 79.5 ± 1.1, 81.7 ± 1.2, 82.2 ± 0.8 and 78.3 ± 1.3 nmol/L, respectively; <it>p </it>< 0.001). Within each region, except for the northeastern part of the country, subjects living inside municipal areas had lower circulating 25(OH)D (central, 77.0 ± 20.9 nmol/L vs 85.0 ± 22.1 nmol/L, <it>p </it>< 0.001; north 79.3 ± 22.1 nmol/L vs 86.8 ± 21.8 nmol/L, <it>p </it>< 0.001; northeast 84.1 ± 23.3 nmol/L vs 87.3 ± 20.9 nmol/L, <it>p </it>= 0.001; south, 76.6 ± 20.5 nmol/L vs 85.2 ± 24.7 nmol/L, <it>p </it>< 0.001). Overall, the prevalence of vitamin D insufficiency was 64.6%, 46.7%, and 33.5% in Bangkok, municipal areas except Bangkok, and outside municipal area in other parts of the country, respectively. In addition, the prevalence of vitamin D insufficiency according to geographical regions was 43.1%, 39.1%, 34.2% and 43.8% in the central, north, northeast and south, respectively. After controlling for covariates in multiple linear regression analysis, the results showed that low serum 25(OH)D levels were associated with being female, younger age, living in urban and Bangkok.</p> <p>Conclusions</p> <p>Vitamin D insufficiency is common and varies across geographical regions in Thailand.</p

Early menopause, association with tobacco smoking, coffee consumption and other lifestyle factors: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Early onset of menopause is a risk factor for several health problems. The objective was primarily to investigate the association between early menopause and current, past active and passive smoking. A second aim was to investigate the association between coffee and alcohol consumption and early menopause.</p> <p>Methods</p> <p>The present population-based cross-sectional study included a sub-sample of 2123 postmenopausal women born in 1940–41 who participated in the Oslo Health Study. Early menopause was defined as menopause occurring at an age of less than 45 years. We applied logistic regression analyses (crude and adjusted odds ratio (OR)) to examine the association between early menopause and selected lifestyle factors.</p> <p>Results</p> <p>Current smoking was significantly associated with early menopause (adj. OR, 1.59; 95% CI, 1.11–2.28). Stopping smoking more than 10 years before menopause considerably reduced the risk of early menopause (adj. OR, 0.13; 95% CI, 0.05–0.33). Total exposure to smoking (the product of number of cigarettes per day and time as a smoker) was positively related to early menopause and, at the highest doses, nearly doubled the odds (adj. OR, 1.93; 95% CI, 1.12–3.30). These data suggest a possible dose-response relationship between total exposure to smoking and early menopause, but no dose-response relationship was detected for the other variables examined. We found no significant association of coffee or alcohol consumption with early menopause. Of the lifestyle factors tested, high educational level (adj. OR, 0.50; 95% CI, 0.34–0.72) and high social participation (adj. OR, 0.60, 95% CI, 0.39–0.98) were negatively associated with early menopause.</p> <p>Conclusion</p> <p>This cross-sectional study shows an association between current smoking and early menopause. The data also suggest that the earlier a woman stops smoking the more protected she is from early menopause. Early menopause was not significantly associated with passive smoking, or alcohol or coffee consumption.</p

Osteoporosis in Men

Produženjem očekivanog trajanja života osteoporoza je postala rastući problem u većini razvijenih zemalja svijeta. U radu se raspravlja o učestalosti, patogenezi, dijagnostičkim kriterijima i mogućnostima liječenja osteoporoze u muškaraca. Svaki treći prijelom kuka događa se u muškaraca, a više od 11 % muškaraca starijih od 50 godina doživi ovaj prijelom. Dijagnoza idiopatske osteoporoze primjenjuje se za muškarce mlađe od 60 godina u kojih nema drugih mogućih uzroka bolesti. U njih je niska mineralna gustoća kosti (BMD) najvećim dijelom posljedica niske vršne koštane mase. U oko 30 % muškaraca nalazi se sekundarna osteoporoza, a involucijska osteoporoza nastaje u muškaraca starijih od 60 godina, kao rezultat smanjenja koncentracije testosterona i IGF-1. S obzirom na rezultate istraživanja koja su pokazala da vrijednost BMD-a u oba spola pruža slične informacije o riziku prijeloma, čini se da se postojeći kriteriji za dijagnozu osteoporoze u žena mogu iskoristiti i za muškarce. U liječenju, bisfosfonati i teriparatid dokazano i značajno povećavaju BMD u muškaraca. Primjena androgena pokazala se učinkovitom u muškaraca s hipogonadizmom, no opravdanost njihove primjene u eugonada još uvijek je predmet rasprava. Povećanjem znanja o metabolizmu kosti i koštanoj pregradnji u novije vrijeme otvorila su se vrata čitavom nizu molekula koje bi u budućnosti mogle postati temelj liječenja osteoporoze u muškaraca.With the prolongation of life expectancy, osteoporosis has become an increasing problem in the majority of developed countries worldwide. The paper discusses the frequency, pathogenesis, diagnostic criteria and treatment options for osteoporosis in men. Every third hip fracture occurs in men, and more than 11 % of the male population over the age of 50 years suffer the fracture. Diagnostic tests for idiopathic osteoporosis are performed in men under 60 years of age without other potential risk factors of developing the disease. In the majority of cases, their low bone mineral density (BMD) is caused by a low peak bone mass. Secondary osteoporosis occurs in about 30 % of men, and involutionary osteoporosis developed in men over 60 years of age results from their decreased testosterone and IGF-1 levels. The study results showing that BMD levels in both sexes provide similar fracture risk information suggest that the existing diagnostic criteria for female osteoporosis can also be employed in men. It has been proved that biphosphonate and teriparitide therapy significantly increase BMD levels in men. The administration of androgens has been shown to be effective in men with hypogonadism, although their validity for patients with eugonadism has not yet been discussed. An improved knowledge of the bone metabolism and bone remodelling has recently opened the door to an extensive series of molecules that may play a key role in the treatment of male osteoporosis in the future

A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: A 6-month study

These data were presented in part at the Second Joint Meeting of the International Bone and Mineral Society (IBMS) and the European Society for Calcified Tissue (ECTS), 25-29 June 2005, Geneva, SwitzerlandObjective: The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis. Methodology: A total of 104 patients (n = 47 teriparatide [20 μg/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (≥ 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study. Results: Teriparatide was associated with a 5.03 ± 4.77% increase in lumbar spine BMD (p < 0.0001, mean ± SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 ± 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, P = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters. Conclusions: Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women. © 2006 Librapharm Limited.link_to_subscribed_fulltex

Responsiveness of gene expression markers of osteoblastic and osteoclastic activity to calcitonin in the appendicular and axial skeleton of the rat in vivo

We have previously shown that calcitonin (CT), an inhibitor of bone resorption, increases vertebral, but not femoral bone density in the rat. To address the physiologic responses associated with these effects on bone mineral density (BMD), we assessed mRNA transcripts reflecting activities of osteoblasts (type I collagen, osteocalcin, osteopontin, and alkaline phosphatase), osteoclasts [tartrate-resistant acid phosphatase (TRAP)], and cell proliferation (histone H4) in the spine and femur of these rats. CT increased spine BMD while increasing type I collagen and decreasing TRAP and histone mRNAs. In the femur, where CT had no effect on BMD, it decreased type I collagen and histone H4 mRNA but did not affect TRAP. CT had no effect on the gene expression of osteocalcin, osteopontin, or alkaline phosphatase at either site. The results indicate that selective alterations in gene expression, as reflected by steady state mRNA levels, are consistent with the changes observed by BMD measurement, and can more clearly define the specific contribution from osteoblast and osteoclast activity. This study demonstrates a heterogeneity in response of the axial and appendicular skeleton to CT, reflected by alterations in gene expression that provide a basis for understanding the observed BMD responses to various pharmacologic interventions

Etidronate inhibits the thyroid hormone-induced bone loss in rats assessed by bone mineral density and messenger ribonucleic acid markers of osteoblast and osteoclast function

TSH-suppressive doses of thyroid hormone are associated with bone loss. We have previously reported that L-T4 decreases femoral, but not vertebral bone mineral density (BMD) in rats. As bisphosphonates are able to decrease bone resorption, especially in high bone turnover states, we investigated the potential effects of etidronate disodium (EHDP) on L-T4-induced bone loss in the rat model by assessing BMD and gene expression of osteoblast (osteocalcin, osteopontin, type I collagen, and alkaline phosphatase), osteoclast (tartrate-resistant acid phosphatase), and cell growth (histone) markers in the skeleton. L-T4 administered for 20 days decreased BMD in the femur, but had no effect on the lumbar spine. EHDP alone had no effect on femoral or vertebral BMD, but did prevent the L-T4-induced bone loss in the femur. L-T4 increased mRNA levels of alkaline phosphatase, tartrate-resistant acid phosphatase, and histone H4 in the femur, but not in the vertebrae. EHDP, which alone had no effect on gene expression in the femur or vertebrae, inhibited the effect of L-T4 on mRNA markers in the femur. The results demonstrate that EHDP can prevent the L-T4-induced decrease in femoral BMD in rats that is associated with the prevention of changes in mRNA markers of osteoclast and osteoblast function. EHDP and other bisphosphonate compounds may be useful in the prevention of thyroid hormone-induced bone loss in humans