Serum parathyroid hormone is associated with increased cortical porosity of the inner transitional zone at the proximal femur in postmenopausal women: the Tromsø Study.

Serum parathyroid hormone (PTH) was associated with increased bone turnover markers and cortical porosity of the inner transitional zone at the proximal femur. These results suggest that PTH through increased intracortical bone turnover leads to trabecularisation of inner cortical bone in postmenopausal women. INTRODUCTION: Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity. METHODS: This case-control study included 211 postmenopausal women, 54-94 years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry. RESULTS: Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p < 0.05). Serum 25(OH)D was not associated with cortical parameters (all, p > 0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness. CONCLUSIONS: These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.

Large Individual Differences in Serum 25-Hydroxyvitamin D Response to Vitamin D Supplementation: Effects of Genetic Factors, Body Mass Index, and Baseline Concentration. Results from a Randomized Controlled Trial.

The main aim of the study was to determine the influence of genetic factors on the serum 25-hydroxyvitamin D response to vitamin D supplementation. The main outcome measure was an increase in serum 25-hydroxyvitamin D after vitamin D supplementation. The patients are part of a randomized controlled trial in individuals with prediabetes assigned to 20 000 IU of vitamin D3 per week or placebo for 12 months. A total of 484 subjects were included in the analyses and genotyped for single nucleotide polymorphisms in the DBP, DHCR7, CYP2R1, and CYP24A1 genes. Single nucleotide polymorphisms from all 4 selected genes were significantly related to baseline serum 25-hydroxyvitamin D concentrations with differences between major and minor homozygote genotypes ranging from 4.4 to 19.2 nmol/l. In the subjects given vitamin D, those with genotypes with the highest baseline 25-hydroxyvitamin D concentration also had the highest 25-hydroxyvitamin D concentration after 12 months, and the increase (delta) in 25-hydroxyvitamin D was significantly related to 3 of the single nucleotide polymorphisms. The increase in serum 25-hydroxyvitamin D was also higher in lean vs. obese subjects, and higher in those with low baseline 25-hydroxyvitamin D concentrations. When combining these 3 factors in a linear regression model, the predicted (and observed) difference in 25-hydroxyvitamin D increase between high and low responders to the supplementation was approximately 60 nmol/l. In conclusion, due to genetic, body mass, and baseline 25-hydroxyvitamin D differences, there are huge individual variations in the serum 25-hydroxyvitamin D response to vitamin D supplementation that could be of clinical importance.

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.

AIMS: We wanted to test the hypothesis that low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with increased risk of developing Type 2 diabetes mellitus (DM) in a population-based cohort during 11 years of follow-up. METHODS: The analyses included 4157 non-smokers and 1962 smokers from the Tromsø Study 1994-95 without diabetes at baseline. Subsequent Type 2 DM was defined using a hospital journal-based end-point registry, completed through the year 2005. Participants were allocated into quartiles of serum 25(OH)D within each month to account for seasonal variation, and serum 25(OH)D values both as a continuous variable and in quartiles were used in Cox regression models. The analyses were stratified by smoking. Adjustments were made for age, sex, body mass index (BMI), physical activity and, in non-smokers, former smoking. RESULTS: Type 2 DM was registered in 183 non-smoking and 64 smoking participants. Using the fourth (highest) quartile of serum 25(OH)D as the reference, non-smoking participants in the third, second and first quartiles had age- and sex-adjusted hazard ratios (95% confidence intervals) of incident Type 2 DM of 1.00 (0.62-1.61), 1.50 (0.97-2.31) and 1.89 (1.25-2.88), respectively, whereas the corresponding values for smokers were 1.79 (0.77-4.19), 2.33 (1.02-5.35) and 2.68 (1.18-6.08). Adjustment for BMI attenuated the hazard ratios, and they were no longer significant. CONCLUSIONS: Baseline serum 25(OH)D was inversely associated with subsequent Type 2 DM in a population-based 11 year follow-up study, but not after adjustment for BMI. Randomized trials are needed to define the possible role of serum 25(OH)D status, and thereby the role of supplementation, in the prevention of Type 2 DM.