Lost relation between blood pressure and serum 25-hydroxyvitamin D

Background: Low serum 25-hydroxyvitamin D (25(OH)D) levels have consistently been associated with hypertension. During the last decades there has been an unexplained reduction in blood pressure (BP) in Western countries. We therefore examined the relation between serum 25(OH)D and BP in the 7th survey of the Tromsø study 2015/2016. Methods: Blood pressure and serum 25(OH)D were measured and life-style factors registered in 15,951 subjects not using BP medication. Results: In unadjusted analyses there was a significant negative association between serum 25(OH)D and systolic and diastolic BP that disappeared after adjusting for relevant confounders. This finding is in contrast to our previous reports on 25(OH)D and BP. We therefore cross-sectionally re-analyzed non-smoking (due to interference by smoking in the 25(OH)D assay) subjects not using BP medication from the 4th survey in 1994/1995 (n ¼ 4108), 6th survey in 2007/ 2008 (n ¼ 7553) and 7th survey 2015/2016 (n ¼ 13,413). Adjusting for age and BMI, there were significant inverse relations between BP and 25(OH)D in the 4th, to a lesser degree in the 6th, and none in the 7th survey. For males the age- and BMI-adjusted differences in systolic BP between those with serum 25(OH)D 100 nmol/L were 6.2 mmHg, 4.1 mmHg and 0.1 mmHg, for the 4th, 6th and 7th surveys, respectively. Conclusions: Concomitant with a substantial reduction in BP from 1994 to 2015, there has been a loss of relation between 25(OH)D and BP which is hard to explain

The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women—A randomized controlled trial

Objective: Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of single nucleotide polymorphisms (SNPs) in genes encoding vitamin D-related enzymes. Design: A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D3 (20 000 IU) or matching placebos to be taken twice a week. Patients: A total of 297 postmenopausal women with osteopenia or osteoporosis. Measurements: Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism. Results: Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L; P<.01). There was no significant difference between the groups in change in muscular strength, balance or quality of life over the intervention period. Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene) were associated with muscle strength and treatment effects. Conclusion: One-year treatment with high-dose vitamin D had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard dose. The association between rs3829251 and muscle strength needs confirmation in other populations

Associations of serum 25-hydroxyvitamin D and subjective sleep measures in an arctic population: Insights from the population-based Tromsø Study

Objective - To investigate the relation between serum 25-hydroxyvitamin D (s-25(OH)D) and subjective sleep measures in an Arctic population (69°N). Methods - Cross-sectional data was collected from 21,083 individuals (aged ≥40 years) participating in the population based Tromsø Study: Tromsø7 (2015–2016). The present study included 20,438 participants, after having excluded respondents missing data on s-25(OH)D (n = 161) and/or subjective sleep measures (including sleep duration, insomnia, and daytime sleepiness)(n = 490). Based on s-25(OH)D (assessed using LC-MS/MS), participants were grouped as deficient (75 nmol/L). Sleep duration was grouped as inadequate (ISD) if Results - In both men and women, s-25(OH)D was positively associated with sleep duration, and compared to the sufficient s-25(OH)D group, the insufficient s-25(OH)D group reported significantly shorter sleep duration in both sexes. There was an increased odds of ISD in both men and women but adjusted for confounding factors this was only significant in women (1.16 [1.03, 1.32], p = .017). In men, there were no significant associations between s-25(OH)D and the remaining sleep measures. Women in the high s-25(OH)D group had lower ESS-scores (−0.28 [-0.47, −0.08], p = .006), but higher odds of insomnia (1.16 [1.01, 1.33], p = .036) compared to women in the sufficient group. Conclusions - In this Arctic population, a tenuous association was found between s-25(OH)D and subjective sleep measures, predominantly in women

Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture-A NOREPOS Population-Based Cohort Study

Immune‐mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post‐vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette‐Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow‐up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01–1.44) and 24% (HR = 1.24, 95% CI 1.03–1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non‐significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune‐mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Effects of vitamin D supplementation on bone turnover markers and other bone-related substances in subjects with vitamin D deficiency

In observational studies, vitamin D deficiency is a risk factor for low bone density and future fractures, whereas a causal relation has been difficult to show in randomized controlled trials (RCTs). Similarly, vitamin D deficiency has been associated with increased bone turnover, but RCTs with vitamin D have not shown conclusive effects. This could be due to inclusion of vitamin D sufficient subjects and low vitamin D doses. In the present study 399 subjects with mean baseline serum 25-hydroxyvitamin D (25(OH)D) 34.0 nmol/L completed a four months intervention with vitamin D3 20,000 IU per week versus placebo. Mean serum 25(OH)D increased to 89.0 nmol/L in the vitamin D group and decreased slightly in the placebo group. A small, but significant, decrease in the bone formation marker procollagen of type 1 amino-terminal propeptide (P1NP) was seen in the vitamin D group as compared to the placebo group (mean delta P1NP -1.2 pg/mL and 1.5 ng/mL, respectively, P  6.5 pmol/L and post-intervention decrease in PTH, the decrease in P1NP was more pronounced, they also exhibited significantly reduced serum CTX-1 and increased serum sclerostin. In conclusion, supplementation with vitamin D appears to suppress bone turnover, possibly mediated by PTH reduction. Our findings need to be confirmed in even larger cohorts with vitamin D insufficient subjects

Undiagnosed diabetes based on HbA 1c by socioeconomic status and healthcare consumption in the Tromsø Study 1994-2016

Introduction - We aimed to investigate whether the proportion of undiagnosed diabetes varies by socioeconomic status and healthcare consumption, in a Norwegian population screened with glycated hemoglobin (HbA1c). Research - design and methods In this cohort study, we studied age-standardized diabetes prevalence using data from men and women aged 40–89 years participating in four surveys of the Tromsø Study with available data on HbA1c and self-reported diabetes: 1994–1995 (n=6720), 2001 (n=5831), 2007–2008 (n=11 987), and 2015–2016 (n=20 170). We defined undiagnosed diabetes as HbA1c ≥6.5% (48 mmol/mol) and no self-reported diabetes. We studied the association of education, income and contact with a general practitioner on undiagnosed diabetes and estimated adjusted prevalence ratio (aPR) from multivariable adjusted (age, sex, body mass index) log-binomial regression. Results - Higher education was associated with lower prevalence of diagnosed and undiagnosed diabetes. Those with secondary and tertiary education had lower prevalence of undiagnosed diabetes (aPR for tertiary vs primary: 0.54, 95% CI: 0.44 to 0.66). Undiagnosed as a proportion of all diabetes was also significantly lower in those with tertiary education (aPR:0.78, 95% CI: 0.65 to 0.93). Household income was also negatively associated with prevalence of undiagnosed diabetes. Across the surveys, approximately 80% of those with undiagnosed diabetes had been in contact with a general practitioner the last year, similar to those without diabetes. Conclusions - Undiagnosed diabetes was lower among participants with higher education. The hypothesis that those with undiagnosed diabetes had been less in contact with a general practitioner was not supported

The association between age at menarche and chronic pain outcomes in women: the Tromsø Study, 2007 to 2016

Sex differences in chronic pain are well established with documented predominance in women. This study assessed relationships between age at menarche and chronic pain, site-specific chronic pain, pain characteristics, and chronic widespread pain (CWP). We used data from the Tromsø Study conducted in 2007 to 2008 and 2015 to 2016 (Tromsø 6 and Tromsø 7 waves) including participants aged 30 to 99 years. The associations between age at menarche and chronic pain were examined in Tromsø 6 (n = 6449), Tromsø 7 (n = 5681), and the combination of Tromsø 6 and Tromsø 7 (n = 12,130). Tromsø 7 data were used further to examine the associations between age at menarche and site-specific chronic pain, 4 pain characteristics (pain duration, pain intensity, episode duration, and episode frequency), and CWP. All analyses were adjusted for body mass index, age, and economic status of the household in childhood. Lower age at menarche was associated with an increased risk of chronic pain in all 3 samples (risk ratio for each year delay in menarche 0.98, 95% CI [0.97 to 0.99] across samples). Risk differences were −0.014, CI 95% (−0.02 to −0.005) in Tromsø 6, −0.011, CI 95% (−0.02 to −0.02) in Tromsø 7, and −0.012, CI 95% (−0.02 to −0.01) in the combined sample. Age at menarche was significantly associated with chronic pain in the neck, abdomen, and both arms, and CWP. Of the 4 pain characteristics, pain duration was statistically significant. We conclude that early menarche is an independent risk factor for pain across a broad spectrum of pain outcomes

Low Serum Levels of 25-Hydroxyvitamin D Predict Hip Fracture in the Elderly: A NOREPOS Study

Background: Despite considerable interest, the relationship between circulating 25-hydroxyvitamin D and the risk of hip fracture is not fully established. Objective: The objective of the study was to study the association between serum 25-hydroxyvitamin D concentrations [s-25(OH)D] and the risk of hip fracture in Norway, a high-latitude country that has some of the highest hip fracture rates worldwide. Methods: A total of 21 774 men and women aged 65–79 years attended 4 community-based health studies during 1994–2001. Information on subsequent hip fractures was retrieved from electronic hospital discharge registers, with a maximum follow-up of 10.7 years. Using a stratified case-cohort design, s-25(OH)D was determined by HPLC-atmospheric pressure chemical ionization-mass spectrometry in stored serum samples in hip fracture cases (n = 1175; 307 men, 868 women) and in gender-stratified random samples (n = 1438). Cox proportional hazards regression adapted for the case-cohort design was performed. Results: We observed an inverse association between s-25(OH)D and hip fracture; those with s-25(OH)D in the lowest quartile (<42.2 nmol/L) had a 38% [95% confidence interval (CI) 9–74%] increased risk of hip fracture compared with the highest quartile (≥67.9 nmol/L) in a model accounting for age, gender, study center, and body mass index. The association was stronger in men than in women: hazard ratio 1.65 (95% CI 1.04–2.61) vs hazard ratio 1.25 (95% CI 0.95–1.65). Conclusion: In this prospective case-cohort study of hip fractures, the largest ever reported, we found an increased risk of hip fracture in subjects in the lowest compared with the highest quartile of serum 25-hydroxyvitamin D. In accordance with the findings of previous community-based studies, low vitamin D status was a modest risk factor for hip fracture.publishedVersio

Circulating sex-steroids and Staphylococcus aureus nasal carriage in a general female population

Objective: Staphylococcus aureus is a major human pathogen, and nasal carriers have an increased risk for infection and disease. The exploration of host determinants for nasal carriage is relevant to decrease infection burden. Former studies demonstrate lower carriage prevalence in women and among users of progestin-only contraceptives. The aim of this study was to investigate the possible associations between circulating sex-steroid hormones and nasal carriage of Staphylococcus aureus in a general population. Methods: In the population-based sixth Tromsø study (2007–2008) nurses collected nasal swab samples from 724 women aged 30–87 not using any exogenous hormones, and 700 of the women had a repeated nasal swab taken (median interval 28 days). We analysed a panel of serum sex-steroids by liquid chromatography tandem mass spectrometry, and collected information about lifestyle, health and anthropometric measures. Multivariable logistic regression was used to study the association between circulating sex-steroids and Staphylococcus aureus carriage (one swab) and persistent carriage (two swabs), while adjusting for potential confounding factors. Women in luteal phase were excluded in the analysis of androgens. Results: Staphylococcus aureus persistent nasal carriage prevalence was 22%. One standard deviation increase in testosterone and bioavailable testosterone was associated with lower odds of persistent nasal carriage, (OR = 0.57; 95% CI = 0.35–0.92 and OR = 0.52, 95% CI = 0.30–0.92) respectively. Analysis stratified by menopause gave similar findings. Persistent carriers had lower average levels of androstenedione and DHEA, however, not statistically significant. Conclusion: This large population-based study supports that women with lower levels of circulating testosterone may have increased probability of Staphylococcus aureus persistent carriage

C3-epimerization of 25-hydroxyvitamin D increases with increasing serum 25-hydroxyvitamin D levels and shows a high degree of tracking over time

Objective: Evaluate the effects of serum 25-hydroxyvitamin D (25(OH)D) levels, vitamin D binding protein (DBP) and genetic factors on C3-epimerization of 25(OH)D and follow the tracking of the epimer during one year. Design: Cross-sectional and longitudinal study. Methods: Data from eight previously conducted, Tromsø based studies (3 observational, 5 randomized controlled trials) were combined. 25(OH)D serum samples were re-analyzed with a LC-MS/MS method that also resolves and measures the metabolite C3-epi-25(OH)D3. Data on vitamin D binding protein (DBP) phenotype (based on single nucleotide polymorphisms (SNPs) rs4588 and rs7041) and genetic determinants for serum 25(OH)D (SNPs rs2282679, rs10741657, rs3829251 and rs6013897) were collected where available. Results: 2219 subjects were included. Median (5th, 95th percentiles) baseline serum values of 25(OH)D3, C3-epi-25(OH)D3, and %-C3-epi-25(OH)D3 were 49.1 (22.1, 92.8) nmol/L, 2.3 (0.9, 6.0) nmol/L and 4.4 (2.7, 8.4) %, respectively. The highest baseline values were 230.5 nmol/L for 25(OH)D3, 79.7 nmol/L for C3-epi-25(OH)D3 and 48.2% for %-C3-epi-25(OH)D3. There was a strong correlation between serum 25(OH)D3 and C3-epi-25(OH)D3. The %-C3-epi-25(OH)D3 value increased with increasing serum 25(OH)D3, but leveled off at ~7% at a 25(OH)D3 concentration of ~120–140 nmol/L. There was a significant degree of tracking for %-C3-epi-25(OH)D3 (correlation coefficient rho between baseline and 1-year values 0.39, P < 0.001). The %-C3-epi-25(OH)D3 level was not related to serum DBP level, DBP phenotype nor to SNPs related to serum 25(OH)D3 level. The serum 25(OH)D3 level could explain less than 3% of %-C3-epi-25(OH)D3 variation. Conclusions: There are considerable individual and reproducible differences in percent C3-epimerization of uncertain clinical importance