Bone density parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women.

OBJECTIVE--To examine the relation between bone density and indices of calcium metabolism including parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women. DESIGN--A cross sectional study. SETTING AND SUBJECTS--138 women volunteers aged 45-65 with no known osteoporosis and unselected for disease status recruited for a dietary assessment study from the community using general practice registers. Volunteer rate was 20%. MAIN OUTCOME MEASURE--Bone mineral density measured with dual energy x ray absorptiometry. RESULTS--Bone density at the lumbar spine and neck and trochanteric regions of the femur was inversely related to serum intact parathyroid hormone concentrations and positively related to serum 25-hydroxyvitamin D concentrations. These associations were independent of possible confounding factors, including age, body mass index, cigarette smoking habit, menopausal status, and use of diuretics and postmenopausal hormone replacement therapy. These associations were apparent throughout the whole distribution of bone density and 25-hydroxyvitamin D and parathyroid hormone concentrations within the normal range, suggesting a physiological relation. CONCLUSIONS--The findings are consistent with the hypothesis that parathyroid hormone and 25-hydroxyvitamin D concentrations influence bone density in middle aged women. Findings from this study together with other work suggest that the role of vitamin D in osteoporosis should not be neglected. The associations with parathyroid hormone also indicate plausible biological mechanisms. The roughly 5-10% difference in bone density between top and bottom tertiles of serum 25-hydroxyvitamin D concentrations, though not large in magnitude, may have considerable public health implications in terms of prevention of osteoporosis and its sequelae, fractures.     

Calcium,Parathyroid Hormone,and Vitamin D in Patients with Primary Hyperparathyroidism: Normograms Developed from 10000 Cases

ObjectiveTo better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism.MethodsIn this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations.ResultsA total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P < .001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL.ConclusionsPatients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase. (Endocr Pract. 2011;17:384-394)     

Indices of calcium metabolism in women with hip fractures

We have assessed indices of calcium metabolism in 41 women with hip fractures and compared them with two elderly control groups. The women with hip fractures had lower serum concentrations of albumin, 25-hydroxyvitamin D and osteocalcin than the controls. Serum concentrations of calcium, alkaline phosphatase and parathyroid hormone, as well as urinary hydroxyproline/creatinine ratios were similar in the three groups of women. The small reduction in serum osteocalcin concentration in fracture patients is consistent with the hypothesis that reduced osteoblast function may contribute to the osteoporosis which results in hip fracture.     

Concentraciones deficientes de vitamina D en pacientes con obesidad mórbida. Estudio de caso-control

ObjectivesRecent studies show a high prevalence of vitamin D deficiency in the general population, especially in the elderly. There are also studies reporting the same observations in the morbidly obese, although few of these studies have compared morbidly obese individuals with non-obese persons. The objectives of this study were to estimate the prevalence of vitamin D deficiency and secondary hyperparathyroidism in both groups and to assess whether there is a relationship between obesity and vitamin D deficiency.MethodsThis study was carried out in 138 patients in the Guadalajara University Hospital (Spain) between December 2008 and December 2009. Of these, 50.7% were morbidly obese and 49.3% were not obese. Fasting blood samples were taken from both groups for determination of 25-hydroxyvitamin D, intact parathyroid hormone, calcium, albumin and phosphorus, among other biochemical parameters.ResultsThe mean concentration of 25-hydroxyvitamin D was 16.6±8.12 ng/ml in the morbidly obese group and 21.9±7.34 ng/ml in the non-obese group (p<0.0001). The prevalence of vitamin D deficiency was 80% in morbidly obese patients and 41% in non-obese patients (p<0.0001). There were no statistically significant differences in concentrations of parathyroid hormone, calcium or phosphorus between the two groups.ConclusionsA high prevalence of vitamin D deficiency was found in both groups studied, although the concentration of 25-hydroxyvitamin D was significantly lower in the morbidly obese. Morbid obesity is closely linked to vitamin D deficiency. To prevent this deficiency, determination of 25-hydroxyvitamin D should be included in clinical practice guidelines for the treatment of obesity.     

Vitamin D and disease prevention with special reference to cardiovascular disease

Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25 nmol/l are frequently observed in various population groups throughout the world. This paper highlights the relationship of vitamin D insufficiency with cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases that account for up to 50% of all deaths in western countries. There is evidence from patients with end-stage renal disease that high PTH concentrations are causally related to cardiovascular morbidity and mortality. Activated vitamin D is able to increase survival in this patient group significantly. Moreover, already slightly enhanced PTH concentrations are associated with ventricular hypertrophy and coronary heart disease in the general population. Experimental studies have demonstrated that a lack of vitamin D action leads to hypertension in mice. Some intervention trials have also shown that vitamin D can reduce blood pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is inversely correlated with blood glucose concentrations and insulin resistance. Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the major factor for an insufficient vitamin D status. Unfortunately, vitamin D content of most foods is negligible. Moreover, fortified foods and over-the-counter supplements usually contain inadequate amounts of vitamin D to increase serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to allow higher amounts of vitamin D in fortified foods and supplements.     

The role of 1,25-dihydroxyvitamin D3 and parathyroid hormone in the regulation of chick renal 25-hydroxyvitamin D3-24-hydroxylase.

A single 325-pmol dose of 1,25-dihydroxyvitamin D₃ given to chicks fed a vitamin D-deficient diet containing 3% calcium and 0.6% phosphorus suppresses renal mitochondrial 25-hydroxyvitamin D₃-1α-hydroxylase and stimulates the 25-hydroxyvitamin D₃-24-hydroxylase as measured by in vitro assay. This alteration in the enzymatic activity takes place over a period of hours. The administration of parathyroid hormone rapidly suppresses the 25-hydroxyvitamin D₃-24-hydroxylase. The alterations in the hydroxylases by parathyroid hormone or 1,25-dihydroxyvitamin D₃ are not related to changes in serum clacium or phosphate but could be related to changes in intracellular levels of these ions. Actinomycin D or cycloheximide given in vivo reduces the 25-hydroxyvitamin D₃-24-hydroxylase activity rapidly which suggests that the turnover of the enzyme and its messenger RNA is rapid (1- and 5-h half-life, respectively). The half-lives of the hydroxylases are sufficiently short to permit a consideration that the regulation by 1,25-dihydroxyvitamin D₃ and parathyroid hormone may involve enzyme synthesis and degradation.     

A comparison of biochemical indices of bone turnover in elderly institutionalized and free-living subjects

Plasma concentrations of calcium-phosphate, alkaline phosphatase, 25-hydroxyvitamin D (25(OH)D) and albumin, and fasting urinary sodium/creatinine (Na/Cr), calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (HPr/Cr) were measured in a survey of 208 Chinese elderly subjects living in chronic care institutions, and compared with values from free-living elderly subjects. Plasma parathyroid hormone estimations were also performed on a subpopulation of women living in an institution.Subjects in institutions had higher urinary HPr/Cr ratios in both men and women, as well as higher urinary Ca/Cr ratios in women, suggesting increased bone resorption. These values show significant variation depending on the degree of mobility. Factors which could contribute to the increased bone loss among institutionalized subjects are: reduced physical activity, reduced exposure to sunlight and hence reduced plasma 25(OH)D concentrations, low calcium intake, protein caloric malnutrition and possibly higher sodium intake. Correction of these factors may reduce the risk of fractures among the elderly living in chronic care institutions.     

Interrelations of calcium-regulating hormones during normal pregnancy.

Profound changes in calcium metabolism occur during pregnancy. The mother has to make available extra calcium for fetal requirements while ensuring that her plasma and bone calcium concentrations are satisfactorily maintained. In a cross-sectional study plasma concentrations of the major calcium-regulating hormones--namely, calcitonin, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-(OH)2D)--were measured to establish their interrelations during normal pregnancy. The major changes observed were increases in the circulating concentrations of 1,25-(OH)2D and calcitonin. Concentrations of parathyroid hormone and 25-OHD remained within the normal range. The increased concentrations of 1,25-(OH)2D enable the increased physiological need for calcium to be met by enhancing intestinal absorption of this element. The simultaneous rise in calcitonin opposes the bone-resorbing activities of 1,25-(OH)2D, thereby protecting the integrity of the maternal skeleton. Maternal calcium homeostasis is thus maintained yet the requirements of the fetus are fulfilled.     

Identifying Parathyroid Hormone Disorders and their Phenotypes through a Bone Health Screening Panel: It's not Simple Vitamin D Deficiency!

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.Abbreviations:25OHD = 25-hydroxyvitamin DAKUH = Aga Khan University HospitalBHSP = bone health screening paneliPTH = intact parathyroid hormonemaxPTH = maximum parathyroid hormoneMBD = metabolic bone diseaseNCHPT = normocalcemic hyperparathyroidismPHPT = primary hyperparathyroidismPTH = parathyroid hormoneSHPT = secondary hyperparathyroidismVDD = vitamin D deficiency     

Regulation of vitamin D metabolism.

Vitamin D can be regarded as a prohormone and its most potent metabolite, 1, 25-dihydroxyvitamin D₃, a hormone which mobilizes calcium and phosphate from bone and intestine. In true hormonal fashion, the biosynthesis of 1, 25-dihydroxyvitamin D₃ by kidney mitochondria is feed-back regulated by serum calcium and serum phosphorus levels. The lack of calcium brings about a secretion of parathyroid hormone which stimulates 1, 25-dihydroxyvitamin D₃ synthesis while low blood phosphorus stimulates 1, 25-dihydroxyvitamin D₃ synthesis even in the absence of the parathyroid glands. For such regulation to occur, vitamin D must be present probably because 1, 25-dihydroxyvitamin D₃ itself is needed for the regulation. The molecular and cellular mechanisms whereby 1, 25-dihydroxyvitamin D₃ synthesis is regulated are unknown despite many recent reports. Likely the elucidation of these mechanisms must await a detailed investigation of the enzymology of the renal 25-hydroxyvitamin D₃-1α-hydroxylase. In addition to the regulation at the 25-hydroxyvitamin D₃-1α-hydroxylase step, vitamin D metabolism is regulated at the hepatic vitamin D-25-hydroxylase level. This regulation is a suppression of the hydroxylase by the hepatic level of 25-hydroxyvitamin D₃ itself by an unknown mechanism. Much remains to be learned concerning the regulation of this newly discovered endocrine system but already the findings are not only relevant to calcium homeostasis but also to an understanding of a variety of metabolic bone diseases.     

Correlating Pre-Operative Vitamin D Status with Post-Thyroidectomy Hypocalcemia

Objective: To examine the relationship between pre-operative vitamin D status and post-thyroidectomy hypocalcemia.Methods: Retrospective study examining 264 total and completion thyroidectomies conducted between 2007 and 2011. Subjects included had a recorded 25-hydroxyvitamin D (25[OH]D) level within 21 days prior to or 1 day following surgery, did not have a primary parathyroid gland disorder, and were not taking 1,25-dihydroxyvitamin D₃ (calcitriol) prior to surgery. Some subjects were repleted with vitamin D pre-operatively if a low 25(OH)D level (typically below 20 ng/mL) was identified. Pre-operative 25(OH)D, concurrent neck dissection, integrity of parathyroid glands, final pathology, postoperative parathyroid hormone (PTH), calcium nadir and repletion, and length of stay were examined.Results: The mean pre-operative 25(OH)D for all subjects was 25 ng/mL, and the overall rate of post-operative hypocalcemia was 37.5%. Lower pre-operative 25(OH)D did not predict postoperative hypocalcemia (P =.96); however, it did predict the need for postoperative 1,25-dihydroxyvitamin D₃ administration (P =.01). Lower postoperative PTH levels (P =.001) were associated with postoperative hypocalcemia.Conclusion: Pre-operative 25(OH)D did not predict a postoperative decrease in serum calcium, although it did predict the need for 1,25-dihydroxyvitamin D₃ therapy in hypocalcemic subjects. We recommend that 25(OH)D be assessed and, if indicated, repleted pre-operatively in patients undergoing total thyroidectomy.Abbreviations: 25(OH)D = 25-hydroxyvitamin D PTH = parathyroid hormone     

Which circulating level of 25-hydroxyvitamin D is appropriate?

Moderate Vitamin D deficiency causes secondary hyperparathyroidism and bone loss, leading to osteoporosis and fractures. Controversy exists which circulating level of 25-hydroxyvitamin D (25OH)D is appropriate. The high incidence of hip fractures at northern latitudes suggest a relationship with Vitamin D deficiency. However, international studies show lower serum 25(OH)D levels in southern than in northern Europe. Serum 25(OH)D was not a risk factor for hip fractures in several epidemiological studies. The required serum 25(OH)D is usually established by assessing the point where serum parathyroid hormone (PTH) starts to rise. This point varied in several studies between 30 and 78 nmol/l. However, interlaboratory variation may also influence the apparent required serum 25(OH)D level. Dietary calcium intake influences serum PTH and serum PTH may influence the turnover of Vitamin D metabolites. A low calcium intake causes an increase of serum PTH and serum 1,25(OH)2D thereby decreasing the half life of serum 25(OH)D. While a low calcium intake may aggravate Vitamin D deficiency, a high calcium intake may have a Vitamin D sparing effect. With current knowledge, a global estimate for the appropriate serum 25(OH)D is 50 nmol/l.     

Severe Vitamin D Deficiency in Arab-American Women Living in Dearborn,Michigan

ObjectiveTo determine the prevalence and degree of 25-hydroxyvitamin D deficiency in a group of Arab- American women in the largest, most-concentrated Arab- American settlement in the United States and to search for correlations with dress, diet, and use of vitamin D–fortified foods and vitamin supplements.MethodsIn this cross-sectional study, Arab-American women, 18 years and older, who attended an ethnic market on April 7 or 14, 2007, were recruited. Participants were interviewed by bilingual English- and Arabic-speaking investigators using a semi-structured interview to assess dress; demographic variables; medical history; medication use; clinical symptoms associated with vitamin D deficiency (eg, joint or bone pain, muscle weakness); and dietary intake of vitamin D from fortified orange juice, milk, and vitamin supplementation. Blood samples were drawn to measure concentrations of serum calcium, creatinine, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxyvitamin D. Participants were initially divided into 2 groups based on whether the woman was veiled and further subdivided into 3 groups on the basis of vitamin D intake from supplemented food sources (milk or vitamin D–fortified orange juice) and vitamin pills: unveiled, veiled and taking supplements, and veiled and taking no supplements.ResultsEighty-seven women participated. Serum 25-hydroxyvitamin D levels were uniformly low, with the highest levels in the unveiled group (median [interquartile range]) (8.5 ng/mL [5.75-13.5 ng/mL]) followed by the veiled, supplemented group (7 ng/mL [4-11.5 ng/mL]) and the veiled, unsupplemented group (4 ng/mL [2-6.8 ng/ mL]). 25-Hydroxyvitamin D levels were lower in women with less experience in the United States and in those with less education. Vitamin D–fortified orange juice consumption had a greater positive predictive effect on serum 25- hydroxyvitamin D levels than either milk or vitamin pills and may possibly serve as a surrogate marker for vitamin D awareness.ConclusionsVitamin D deficiency, as assessed by 25-hydroxyvitamin D concentrations, is endemic in a sample of Arab-American women living in Dearborn, Michigan. These findings potentially identify an important health problem in the largest, most-concentrated Arab- American population in the United States. (Endocr Pract. 2009;15:35-40)     

Dietary content may prevent secondary hyperparathyroidism in female rhesus monkeys (Macaca mulatta)

Macaque laboratory chows provide relatively more calcium (Ca) and vitamin D (D) than human diets; this may influence skeletal aging. To evaluate this possibility, parameters of skeletal relevance in premenopausal and naturally postmenopausal rhesus monkeys were measured in a cross-sectional study. Serum osteocalcin (Oc) was elevated in the postmenopausal group (P < 0.01), but levels of parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) were not different. Subsequently, in premenopausal animals, dietary Ca and/or D intake was reduced to optimal human levels for 8 weeks prior to the evaluation of the skeletal parameters. Serum 25OHD concentration was reduced (P < 0.01) and a trend (P=0.10) towards increased PTH was observed in both low D groups. In addition, serum alkaline phosphatase (ALP) levels were increased in the low Ca group (P < 0.01). In conclusion, skeletal turnover, as measured by serum Oc, was increased in naturally postmenopausal rhesus monkeys in the absence of hyperparathyroidism. Dietary D reduction causes a decline in serum 25OHD and an upward trend in PTH.     

YM175, a new bisphosphonate, increases serum 1,25-dihydroxyvitamin D in rats via stimulating renal 1-hydroxylase activity

Effect of YM175, a new bisphosphonate, on vitamin D metabolism was studied in rats. When animals were treated with the compound, serum 1,25-dihydroxyvitamin D increased in a dose dependent manner. The effect was also detected in thyroparathyroidectomized animals. The effect appears to be due to the stimulation of renal production of the hormone, since renal 1-hydroxylase was also elevated in these animals. However, when kidneys were incubated with YM175 and then renal 1-hydroxylase activity was examined, the enzyme activity was not different from that of non-treated control kidney. We conclude therefore that YM175 indirectly stimulates renal 25-hydroxyvitamin D-1-hydroxylase by increasing circulating parathyroid hormone via an unknown mechanism independent of parathyroid hormone. This is the first direct demonstration of increase in the renal production of 1,25-dihydroxyvitamin D resulting from bisphosphonate treatment.     

Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults

Background

Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections.

Methodology/Findings

In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill.

Conclusions/Significance

Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese.     

Vitamin D-Binding Protein in Healthy Pre- and Postmenopausal Women: Relationship with Estradiol Concentrations

Objective: To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women.Methods: In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels.Results: Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in prethan postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05).Conclusion: Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.Abbreviations: 25OHD = 25-hydroxyvitamin D BMI = body mass index CV = coefficient of variation DBP = vitamin D–binding protein PTH = parathyroid hormone SHBG = sex hormone–binding globulin     

Seasonal Genetic Influence on Serum 25-Hydroxyvitamin D Levels: A Twin Study

Background

Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations.

Methodology/Principal findings

204 same-sex twins, aged 39–85 years and living at northern latitude 60°, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0–88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3–32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48–86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season.

Conclusions/Significance

There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.     

The Use of Vitamins and Minerals in Skeletal Health: American Association of Clinical Endocrinologists and the American College of Endocrinology Position Statement

Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; CV = cardiovascular; GI = gastrointestinal; IOM = Institute of Medicine; PTH = parathyroid hormone; RCT = randomized controlled trial; αTF = α-tocopherol; ucOC = undercarboxylated osteocalcin; VKA = vitamin K antagonist; WHI = Women's Health Initiative