Vitamin D and its binding protein Gc: long-term variability in peri- and postmenopausal women with and without hormone replacement therapy.

OBJECTIVE: Measurement of plasma 25-hydroxyvitamin D (25OHD) level is often used to evaluate a patient's vitamin D status. The purpose of this study was to investigate the variability in individual plasma 25OHD- and vitamin D-binding protein- (Gc) levels over a 5-year period in postmenopausal women with and without hormone replacement therapy (HRT). MATERIAL AND METHODS: A total of 187 women were followed-up for 5 years. At baseline, 89 women were allocated to treatment with HRT, given orally. Measurements were performed at baseline and after 1, 2 and 5 years of follow-up. RESULTS: At baseline, 25OHD levels were positively associated with sunbathing and use of vitamin D supplements, and inversely associated with smoking. HRT therapy increased plasma levels of Gc (+8 %) but did not affect 25OHD levels or the free 25OHD index (molar ratio of 25OHD- to Gc levels). Among those classified in the lowest 25OHD tertile at baseline, 40 % remained in the lowest tertile during all subsequent measurement time-points. Similarly, 32 % of those classified in the highest baseline tertile remained in the highest tertile during all subsequent measurements. Use of the free 25OHD index showed similar results. No independent predictors of changes in vitamin D tertiles during follow-up were identified, which suggests that the observed variation was caused by the intra-individual variation in measured parameters. For all participants, the within-patient variability in 25OHD measurements was between 13 % and 19 %. CONCLUSIONS: In healthy postmenopausal women, HRT increases Gc levels. Owing to the high intra-individual variation in plasma 25OHD, it seems questionable to use a single estimate as a predictor of individual vitamin D status.

Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women.

The major transporter of vitamin D metabolites in the circulation is the multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, vitamin D-binding protein, or DBP. There are several phenotypes of Gc, and we examined the influence of Gc phenotype and Gc concentration on vitamin D status. By using isoelectric focusing we identified the Gc phenotype of 595 caucasian recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS). We measured plasma concentration of Gc by immunonephelometry (coefficient of variation [CV] < 5%), 25-hydroxy vitamin D (25OHD) by a competitive protein-binding assay (CV 10%), and 1,25-dihydroxy-vitamin D (1,25(OH)(2)D) by a radioimmunoassay (CV 6--14%), and calculated index as the molar ratio of vitamin concentration divided by Gc concentration. Plasma levels of Gc, 25OHD, 25OHD index, and 1,25(OH)(2)D, but not 1,25(OH)(2)D index, differed significantly between women with different Gc phenotype, being highest in Gc1-1, intermediate in Gc1-2, and lowest in Gc2-2. In multiple regression analysis, Gc concentration was an independent predictor of 1,25(OH)(2)D, whereas Gc phenotype was a significant predictor of 25OHD concentration, even after adjustment for the effects of season, sunbathing habits, skin thickness, use of vitamin supplements, smoking, and body mass index (BMI). Plasma parathyroid hormone (PTH) level did not differ between Gc phenotypes. Despite the fact that more than 60% of the women with Gc phenotype Gc2-2 had plasma 25OHD levels of less than 50 nmol/L none of them had plasma PTH higher than reference limits. Bone mineral content (BMC), Bone mineral density (BMD), and bone markers did not differ between Gc phenotypes. In conclusion, plasma 1,25(OH)(2)D, 25OHD, and 25OHD index are related to Gc phenotype, and we speculate that the thresholds for vitamin D sufficiency differ between Gc phenotypes.

Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes.

We studied the influence of age, gender, latitude, season, diet and ethnicity on plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D-binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46 Greenlanders living in Nuuk (64 degrees N) on a traditional fare (group A), 45 Greenlanders living in Nuuk on a westernized fare (group B), 54 Greenlanders (group C), and 43 Danes (Group D) living in Denmark (55 degrees N) on a westernized fare. Blood specimens were drawn both summer and winter. Vitamin D insufficiency (plasma 25 OHD <40 nmol/l) was common in all four study groups during summer (23-74%) and winter (42-81%). Compared to groups A and D, vitamin D insufficiency was significantly more frequent in groups B and C. In all groups, summer levels of 25 OHD were above winter levels. Multiple regression analysis revealed a significant effect of ethnicity. Compared to Danes, Greenlanders had higher 1,25-dihydroxyvitamin D levels, but lower 25 OHD and PTH levels despite relatively low plasma calcium concentrations. In addition to ethnicity, 25(OH)D levels were influenced by age, season (summer > winter), and diet (a traditional Inuit diet>westernized diet). Ethnic differences exist between Greenlanders and Danes. Our results suggest that Greenlanders may have an inherent lower "set-point" for calcium-regulated PTH release or an enhanced renal 1,25(OH)(2)D production. In addition to ethnicity, age, season, and diet were important determinants of vitamin D status. Changes from a traditional to a westernized fare are associated with a reduced vitamin D status in Greenlanders. Vitamin D supplementation should be considered.