Nina Emaus

Tracking of Serum 25-Hydroxyvitamin D Levels During 14 Years in a Population-based Study and During 12 Months in an Intervention Study

Low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with risk factors for cardiovascular disease, and they also appear to predict later development of type 2 diabetes, cancer, and an increased mortality rate. These predictions are all based on a single 25(OH)D measurement, but so far there are no known reports on tracking of serum 25(OH)D levels. In the present Norwegian study, serum 25(OH)D levels were measured 1) in 2,668 subjects in the 1994 and 2008 Tromsø surveys and 2) every third month for 1 year in 94 subjects randomly assigned to placebo in a vitamin D intervention study. There was a marked seasonal variation in 25(OH)D, and, depending on the method of adjusting for season, the correlation coefficient between serum 25(OH)D measurements from 1994 and 2008 ranged from 0.42 to 0.52. In the 1-year intervention study, the correlation between baseline and 12-month values was 0.80. Apart from the effect of season, changes in weight, intake of vitamin D, and physical activity were related to change in serum 25(OH)D levels. Tracking of serum 25(OH)D appears similar to that for blood pressure and serum lipids, and it provides some support for the use of a single 25(OH)D measurement to predict future health outcomes.

High serum 25-hydroxyvitamin D concentrations are associated with a favorable serum lipid profile

Background/Objectives:Low serum 25-hydroxyvitamin D (25(OH)D) concentrations are related to increased mortality. One possible explanation could be an association between serum 25(OH)D and serum lipids.Subjects/Methods:The study was performed at the University of Tromsø, Northern Norway. In total, 8018 nonsmoking and 2087 smoking subjects were included in a cross-sectional study performed in 2008, and 1762 nonsmoking and 397 smoking subjects in a longitudinal study from 1994/1995 to 2008. Nonfasting serum 25(OH)D, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio and triacylglycerol (TAG) were measured.Results:After adjustment for gender, age, sample month and body mass index in the cross-sectional study, there was a significant increase in serum TC, HDL-C and LDL-C, and a significant decrease in serum LDL-C/HDL-C ratio and TAG across increasing serum 25(OH)D quartiles. For serum HDL-C and TAG in nonsmokers the differences between the means for the highest and lowest serum 25(OH)D quartiles were 6.0 and 18.5%, respectively. In the longitudinal study, an increase in serum 25(OH)D was associated with a significant decrease in serum TAG.Conclusions:There is a cross-sectional association between serum 25(OH)D and serum lipids, and a longitudinal association over 14 years between serum 25(OH)D and TAG, which may contribute to explain the relation between low serum 25(OH)D concentrations and mortality.

Serum 25-Hydroxyvitamin D Levels Are Strongly Related to Systolic Blood Pressure But Do Not Predict Future Hypertension

Vitamin D receptors have been detected in vascular smooth muscle cells, and 1,25-dihydroxyvitamin D inhibits the renin mRNA expression. Epidemiological studies show an inverse relation between serum 25-hydoxyvitamin D levels and blood pressure, and low serum 25-hydoxyvitamin D levels are reported to be predictors of future development of hypertension. This may indicate an important role for vitamin D in blood pressure regulation. In the present study, 25-hydoxyvitamin D was measured in sera collected in 1994 from 4125 subjects who did not use blood pressure medication, and thereafter measurement was repeated in 2008 for 2385 of these subjects. In sera from 1994 there was a significant decrease in age, body mass index, and systolic blood pressure and a significant increase in physical activity score across increasing 25-hydoxyvitamin D quartiles. After adjusting for sex, age, body mass index, and physical activity, the difference in systolic blood pressure between the lowest and highest serum 25-hydoxyvitamin D quartiles was 3.6 mm Hg. After adjustment for confounders, serum 25-hydoxyvitamin D from 1994 did not predict future hypertension or increase in blood pressure, nor was there any significant association between change in serum 25-hydoxyvitamin D from 1994 to 2008 and change in blood pressure. Our results do not support a causal role for vitamin D in blood pressure regulation, and large randomized clinical trials, preferably including subjects with hypertension and/or low serum 25-hydoxyvitamin D levels, are greatly needed to clarify whether vitamin D supplementation affects the blood pressure.

Baseline serum 25‐hydroxyvitamin D concentrations in the Tromsø Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow‐up

Diabet. Med. 27, 1107–1115 (2010)

The Relationship between Serum TSH and Bone Mineral Density in Men and Postmenopausal Women: The Tromsø Study

BACKGROUND Hyperthyroidism is associated with osteoporosis, and it has recently been suggested that thyroid-stimulating hormone (TSH) has bone protective properties. We wanted to explore the relationship between serum TSH and bone mineral density (BMD) in a healthy population. METHODS This study included 993 postmenopausal females and 968 males with valid measurements of BMD at the hip and forearm in the fifth Tromsø study conducted in 2001. Participants with major diseases or medication affecting BMD or thyroid function were excluded. The subjects were divided into six different groups based on the 2.5 and 97.5 percentiles of serum TSH and the quartiles in between. Multiple linear regression adjusting for age; weight; height; smoking status; physical activity level; and for women, use of hormonal replacement therapy was used in the analyses. RESULTS After multivariate adjustment, the 28 men and 18 women with serum TSH below the 2.5 percentile had significantly lower BMD at the ultradistal (women) and distal (both sexes) forearm than the 921 men and 950 women with serum TSH in the normal range. Also, the 25 postmenopausal women with serum TSH above the 97.5 percentile had significantly higher BMD at the femoral neck than women with serum TSH in the normal range. Across the normal range of serum TSH, there was no association between TSH and BMD, and serum TSH as a continuous variable had no effect on BMD in the multiple linear regression model. CONCLUSIONS Within the normal range of serum TSH, serum TSH was not associated with BMD. The small groups of men and women with serum TSH consistent with hyperthyroidism had lower BMD at the forearm than those with serum TSH in the normal range.

Effect of smoking on the serum levels of 25-hydroxyvitamin D depends on the assay employed

OBJECTIVE Because we found higher serum 25-hydroxyvitamin D (25(OH)D) levels among smokers than among non-smokers with analyses using an electrochemiluminescence immunoassay (ECLIA) from Roche, the purpose of the present study was to examine whether this difference between smokers and non-smokers was maintained using other serum 25(OH)D assays. DESIGN A cross-sectional population-based study on 6932 participants from the Tromsø study, 1994-1995, and one validation study comparing six different serum 25(OH)D assays in 53 non-smokers and 54 smokers were performed. METHODS The association between smoking, season and serum 25(OH)D as measured by ECLIA (Roche) was assessed in the population-based study using general linear models with multivariate adjustments. In the validation study, serum levels of 25(OH)D were analysed with liquid chromatography coupled with mass spectrometry assay from two different laboratories, RIA (DiaSorin), HPLC, RIA (IDS) and ECLIA (Roche). T-tests and linear mixed model analyses were performed to compare the serum 25(OH)D levels in smokers and non-smokers within and between the methods. RESULTS In the population-based study, the serum levels of 25(OH)D using the ECLIA method were 51.9, 53.2 and 72.0 nmol/l in never, former and current smokers (P<0.01). In the validation study, the serum concentration of 25(OH)D was 10.3 nmol/l higher in smokers than in non-smokers (P<0.01) using the ECLIA (Roche), while non-significantly lower serum levels of 25(OH)D were found in smokers using the other five methods. CONCLUSIONS These two studies indicate that the ECLIA (Roche) overestimates serum 25(OH)D levels in smokers by unknown mechanisms. If confirmed, this might have clinical consequences, and the issue needs further exploration.

Mortality following the first hip fracture in Norwegian women and men (1999-2008). A NOREPOS study

Hip fractures are associated with increased mortality and their incidence in Norway is one of the highest worldwide. The aim of this nationwide study was to examine short- and long-term mortality after hip fractures, burden of disease (attributable fraction and potential years of life lost), and time trends in mortality compared to the total Norwegian population. Information on incident hip fractures between 1999 and 2008 in all persons aged 50 years and older was collected from Norwegian hospitals. Death and emigration dates of the hip fracture patients were obtained through 31 December 2010. Standardized mortality ratios (SMRs) were calculated and Poisson regression analyses were used for the estimation of time trends in SMRs. Among the 81,867 patients with a first hip fracture, the 1-year excess mortality was 4.6-fold higher in men, and 2.8-fold higher in women compared to the general population. Although the highest excess mortality was observed during the first two weeks post fracture, the excess risk persisted for twelve years. Mortality rates post hip fracture were higher in men compared to women in all age groups studied. In both genders aged 50 years and older, approximately 5% of the total mortality in the population was related to hip fractures. The largest proportion of the potential life-years lost was in the relatively young-old, i.e. less than 80 years. In men, the 1-year absolute mortality rates post hip fracture declined significantly between 1999 and 2008, by contrast, the mortality in women increased significantly relatively to the population mortality.

Lifestyle Impact on Lifetime Bone Loss in Women and Men The Tromsø Study

A physically active, nonsmoking lifestyle with weight maintenance positively influences bone health. The authors estimated the effect of lifestyles on peak bone mass and lifetime bone loss in the Tromsø Study, Norway. Bone mineral density (BMD) was measured at distal and ultradistal forearm sites with single x-ray absorptiometric devices in 7,948 men and women aged 24-84 years in 1994-1995 and repeated in 2001 in 6,182 subjects. BMD was significantly higher at peak than at old age. However, the difference, estimated as lifetime loss, varied between lifestyle groups. Lifetime loss in nonsmoking, physically active men with a body mass index of 25 kg/m(2) compared with smoking, inactive, and lean men was 15.9% and 25.9% at the distal site and 17.5% and 29.7% at the ultradistal site, respectively. In women, the corresponding loss estimates were 34.4% and 45.7% and 35.6% and 55.7%, respectively. The differences in BMD at the age of 80 years correspond to an increased forearm fracture risk of 69% in men and 85% in women with greatest bone loss. A lifestyle including nonsmoking, a high physical activity level, and a high body weight reduces bone loss and fracture risk in both sexes, with increasing effect from peak bone mass to old age.

Prevalence of vertebral fractures in women and men in the population-based Tromsø Study

BackgroundOsteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway.MethodsData was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant.ResultsThe prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (p = 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures.ConclusionsThe prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.

Circulating Sex Steroids, Sex Hormone-Binding Globulin, and Longitudinal Changes in Forearm Bone Mineral Density in Postmenopausal Women and Men: The Tromsø Study

Bone loss during advancing age in women and men is partly the result of sex steroid deficiency. As the contribution of circulating sex steroids and sex hormone-binding globulin (SHBG) to bone loss remains uncertain, we sought to determine whether levels of sex steroids or SHBG predict change in bone mineral density (BMD) in women and men. A population-based study in the city of Tromsø of 6.5 years’ duration (range 5.4-7.4) included 927 postmenopausal women aged 37–80 years and 894 men aged 25–80 years. Total estradiol and testosterone, calculated free levels, and SHBG were measured at baseline, and BMD change at the distal forearm was determined using BMD measurements in 1994–1995 and 2001. Bone loss was detected in postmenopausal women and men. Free estradiol and SHBG predicted age-adjusted bone loss in postmenopausal women, but only free estradiol was associated after further adjustment for body mass index and smoking in mixed models (P < 0.05). After same adjustment, only SHBG persisted as a significant independent predictor of bone loss in men (P < 0.001). However, only 1% of the variance in bone loss was accounted for by these measurements. We therefore conclude that the relations between sex steroids and bone loss are weak and measurements of sex steroids are unlikely to assist in clinical decision making.