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Biomedical subjects

Leif Mosekilde

Publications and source records attributed to Leif Mosekilde.

At least 37 records · Page 2Linked to original sources
PubMed2005

Vitamin D and calcium supplementation prevents severe falls in elderly community-dwelling women: a pragmatic population-based 3-year intervention study.

BACKGROUND AND AIMS: We evaluated the effect of two programs for the prevention of falls leading to acute hospital admission in a population of elderly community-dwelling Danish residents. METHODS: This was a factorial, pragmatic, intervention study. We included 9605 community-dwelling city residents aged 66+ years. We offered a prevention program consisting of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU (10 microg) of vitamin-D3 to a total of 4957 participants. The remaining 5063 participants were offered home safety inspection with dietary and health advice, or no intervention. RESULTS: The Calcium and Vitamin D program was followed by 50.3% and the Environmental and Health Program by 46.4%. According to a multivariate analysis including age, marital status and intervention program, female residents who followed the Calcium and Vitamin D Program had a 12% risk reduction in severe falls (RR 0.88; 95% CI 0.79-0.98; p < 0.05; NNT 9). CONCLUSIONS: The present study supports the hypothesis that vitamin D and calcium supplementation prevent falls leading to acute hospitalization in community-dwelling elderly females in a northern European region known to be deficient in vitamin D.

Accidental Falls↗
PubMed2005

Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study.

We have previously found BMD and fracture risk to be significantly associated with the MTHFR (C677T) polymorphism in healthy postmenopausal women in the first years after menopause. Since then, other cohort studies have suggested that sufficient intake of riboflavin and/or folate may have the potential to prevent development of low BMD in women with the TT genotype. This could to some extent explain why this polymorphism is associated with low BMD or fracture in some study populations and not in others. It would also indicate that fractures associated with the TT genotype could be preventable by vitamin B supplementation. We have, therefore, reviewed baseline food record data from our original study to determine if BMD and fracture associations with the MTHFR genotype depended on the intake of folate, riboflavin, or other members of the vitamin B complex, associated with homocysteine metabolism. We analyzed genotype, BMD, and dietary records from 1700 healthy postmenopausal women who participated in the DOPS study. For the assessment of fracture risk, we used longitudinal observations from 854 women in the control group who remained compliant with their initial allocation of no treatment. Riboflavin intake was significantly correlated with femoral neck (FN) BMD in women with the TT genotype (r = 0.24, P < 0.01). FN and lumbar spine (LS) BMD were only associated with the MTHFR genotype in the lowest quartile of riboflavin intake. At the FN, similar threshold effects were shown for folate, vitamin B12, and vitamin B6. Among these vitamin B complex members, stepwise regression analysis identified riboflavin as the only significant predictor of FN BMD in the TT genotype. In conclusion, we confirm reports that BMD in the MTHFR TT genotype is only significantly reduced in the lowest quartile of riboflavin, B12, B6, and folate intake, at least at the time of menopause. Vitamin B supplementation would only be expected to benefit BMD in about 2% of the population, i.e., those with the TT genotype and low vitamin B intake.

Bone Density↗
PubMed2005

Vitamin D and the elderly.

This review summarizes current knowledge on vitamin D status in the elderly with special attention to definition and prevalence of vitamin D insufficiency and deficiency, relationships between vitamin D status and various diseases common in the elderly, and the effects of intervention with vitamin D or vitamin D and calcium. Individual vitamin D status is usually estimated by measuring plasma 25-hydroxyvitamin D (25OHD) levels. However, reference values from normal populations are not applicable for the definition of vitamin D insufficiency or deficiency. Instead vitamin D insufficiency is defined as the lowest threshold value for plasma 25OHD (around 50 nmol/l) that prevents secondary hyperparathyroidism, increased bone turnover, bone mineral loss, or seasonal variations in plasma PTH. Vitamin D deficiency is defined as values below 25 nmol/l. Using these definitions vitamin D deficiency is common among community-dwelling elderly in the developed countries at higher latitudes and very common among institutionalized elderly, geriatric patients and patients with hip fractures. Vitamin D deficiency is an established risk factor for osteoporosis, falls and fractures. Clinical trials have demonstrated that 800 IU (20 microg) per day of vitamin D in combination with 1200 mg calcium effectively reduces the risk of falls and fractures in institutionalized patients. Furthermore, 400 IU (10 microg) per day in combination with 1000 mg calcium or 100 000 IU orally every fourth month without calcium reduces fracture risk in individuals over 65 years of age living at home. Yearly injections of vitamin D seem to have no effect on fracture risk probably because of reduced bioavailability. Simulation studies suggest that fortification of food cannot provide sufficient vitamin D to the elderly without exceeding present conventional safety levels for children. A combination of fortification and individual supplementation is proposed. It is argued that all official programmes should be evaluated scientifically. Epidemiological studies suggest that vitamin D insufficiency is related to a number of other disorders frequently observed among the elderly, such as breast, prostate and colon cancers, type 2 diabetes, and cardiovascular disorders including hypertension. However, apart from hypertension, causality has not been established through randomized intervention studies. It seems that 800 IU (20 microg) vitamin D per day in combination with calcium reduces systolic blood pressure in elderly women.

Accidental Falls↗
PubMed2005

Effect of growth hormone and 17beta-oestradiol treatment on metabolism and body composition in girls with Turner syndrome.

OBJECTIVE: Girls with Turner syndrome (TS) receive GH treatment during childhood, and in adolescence this treatment may be combined with oestradiol. We have studied the effects of this combined treatment on metabolism and body composition. MATERIAL AND METHODS: We performed a double-blind, placebo-controlled, randomized, crossover study. All girls with TS (n = 8, 16 +/- 2 years) were treated with placebo + placebo, GH + placebo or GH + 17beta-oestradiol for 2 months, and were studied at the end of each period. Controls (n = 10, 14 +/- 2 years) were studied once without treatment. Twenty-four-hour sampling of oestradiol, growth factors, insulin, glucose, lipolytic and gluconeogenic precursors was performed, followed by an oral glucose tolerance test (OGTT) and assessment of body composition and mineral content. RESULTS: GH induced insulin resistance, which was not aggravated further by concomitant oestradiol treatment. The 24-h integrated serum 17beta-oestradiol was reduced compared to controls (0.58 +/- 0.32 vs. 2.81 +/- 2.78 nmol/l/24 h, P = 0.032), but increased during GH + oestrogen (E2) treatment without reaching control levels, while GH + placebo caused a further reduction (anova, P = 0.008). Total fat mass was increased in girls with TS compared with controls (P = 0.009), while lean body mass (P = 0.02) and bone mineral content (P = 0.04) was decreased, with specific regional characteristics in body composition. CONCLUSION: GH treatment induces insulin resistance and changes in body composition in TS, which is not further compromised by concomitant oestradiol treatment. Body composition is changed in TS, with specific regional changes, in comparison with controls. Integrated 24-h oestradiol is low in TS, and is only partially restored during treatment with standard doses of 17beta-oestradiol.

Adolescent↗
PubMed2004

Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes.

CONTEXT: Both bone mineral density (BMD) and fracture risk have a strong genetic component. Estrogen receptor alpha (ESR1) is a candidate gene for osteoporosis, but previous studies of ESR1 polymorphisms in this field were hampered by small sample size, lack of standardization, and inconclusive results. OBJECTIVE: To generate large-scale evidence on whether 3 common ESR1 polymorphisms (intron 1 polymorphisms XbaI [dbSNP: rs9340799] and PvuII [dbSNP: rs2234693] and promoter TA repeats microsatellite) and haplotypes thereof are associated with BMD and fractures. DESIGN AND SETTING: Meta-analysis of individual-level data involving standardized genotyping of 18 917 individuals in 8 European centers. MAIN OUTCOME MEASURES: BMD of femoral neck and lumbar spine; all fractures and vertebral fractures by genotype. RESULTS: No between-center heterogeneity was observed for any outcome in any genetic contrast. None of the 3 polymorphisms or haplotypes had any statistically significant effect on BMD in adjusted or unadjusted analyses, and estimated differences between genetic contrasts were 0.01 g/cm2 or less. Conversely, we found significant reductions in fracture risk. In women homozygous for the absence of an XbaI recognition site, the adjusted odds of all fractures were reduced by 19% (odds ratio, 0.81 [95% CI, 0.71-0.93]; P = .002) and vertebral fractures by 35% (odds ratio, 0.65 [95% CI, 0.49-0.87]; P = .003). Effects on fractures were independent of BMD and unaltered in adjusted analyses. No significant effects on fracture risk were seen for PvuII and TA repeats. CONCLUSIONS: ESR1 is a susceptibility gene for fractures, and XbaI determines fracture risk by mechanisms independent of BMD. Our study demonstrates the value of adequately powered studies with standardized genotyping and clinical outcomes in defining effects of common genetic variants on complex diseases.

Aged↗
PubMed2004

Fracture risk in perimenopausal women treated with beta-blockers.

beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study. Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture risk (OR(adj) 3.3; 95% CI: 1.1-9.4). Analyses on duration of treatment showed that women who had been treated for more than 8 years had a higher fracture risk (OR(adj) 5.3; 95% CI: 1.1-26.3) than those treated for less than 8 years (OR(adj) 2.4; 95% CI: 0.6-9.5). In addition, cross-sectional data showed 20% lower serum osteocalcin levels (an osteoblastic marker of bone formation) in women treated with beta-blockers compared to untreated women (P < 0.001), whereas BMD at the lumbar spine and femoral neck did not differ between groups. beta-Blockers may decrease the activity of bone-forming cells and thereby increase fracture risk. However, confirmative studies and studies exploring mechanisms of action are needed.

Adrenergic beta-Antagonists↗