Genetic Contribution to Bone Metabolism, Calcium Excretion, and Vitamin D and Parathyroid Hormone Regulation

Hunter, David J.; Lange, Marlies de; Snieder, Harold; Macgregor, Alexander; Swaminathan, R.; Thakker, R V; Spector, Tim D.

doi:10.1359/jbmr.2001.16.2.371

Cited by 218 publications

(153 citation statements)

References 37 publications

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“…Thus, the changes observed in these markers during bed rest are more clearly related to bed rest itself and/or the LBNP exercise. The heritability of these markers of bone resorption also provides a biochemical explanation for previously documented heritability of bone health [1,7,16,24,40]. The relatively high between-subject variability in bone markers is frequently criticized as limiting their utility, but our data suggest that the variability is likely related to genetics, and that studies to determine the causes of variability may reveal more about bone metabolism than expected.…”

Section: Discussionsupporting

confidence: 56%

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

Zwart

Hargens

Lee

et al. 2007

Bone

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Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined the potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest (BR) and on BR days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism, and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased (P < 0.001); parathyroid hormone (P = 0.06), bone-specific alkaline phosphatase (P = 0.06), and 1,25-dihydroxyvitamin D (P = 0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 for the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously-published results had Sources of support: This study was funded by NASA through grant NAG 9-1425 and by NIH through grant GCRC M01-RR00827 to UCSD.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers. NIH Public Access

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Section: Discussionsupporting

confidence: 56%

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

Zwart

Hargens

Lee

et al. 2007

Bone

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“…It is possible that some of the variability between studies in the predictors of response to supplementation may be due to the intercorrelation of such variables and the impact of collinearity in model building. Overall, our model for baseline concentrations contained 17 factors that explained 32% of the variability in baseline serum 25(OH)D. We confirmed the observations of others that baseline concentrations reflect a variety of personal characteristics; nutritional, behavioral and lifestyle factors; and measures of sun exposure (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)42). Our finding of an association between glucocorticoid use and lower serum 25(OH)D concentrations adds to mixed evidence from previous studies.…”

Section: Discussionsupporting

confidence: 86%

“…Although the definition of an adequate serum concentration remains controversial (12 ng/mL) (5,6), it has been argued that one-quarter of Americans have inadequate serum concentrations of 25- (12)(13)(14)(15)(16)(17)(18)(19)(20) ng/mL), and 8% are deficient (<12 ng/mL) (7,8). However, the National Academy of Medicine (NAM) made relatively minor changes to DRIs in 2010, stating that 2016 American Society for Nutrition.…”

Section: Introductionmentioning

confidence: 99%

“…Many factors are known to be associated with serum 25(OH)D concentrations, including sun exposure, BMI, skin pigmentation, medications, and comorbidities (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), but, to our knowledge, there is limited evidence on a few factors that may affect the magnitude of serum response to cholecalciferol supplementation, e.g., baseline serum 25(OH)D, BMI, age, calcium intake, and season (27,28). The NAM provides intake recommendations by age and sex, but it is unclear whether supplementation should be varied according to vitamin D status, weight, or other factors (7).…”

Section: Introductionmentioning

confidence: 99%

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Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

Rees

Mott

Barry

et al. 2016

The Journal of Nutrition

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“…The determinants of vitamin D status have been described, with season and dietary intake being identified as the primary contributors (Burnand et al, 1992;Jacques et al, 1997). The heritability of vitamin D status has been estimated at 43% in a sample of primarily female twins (Hunter et al, 2001). The heritability of vitamin K status is unknown, and to our knowledge there are no reports of the nongenetic determinants and heritability of vitamin K and vitamin D status in the same population.…”

Section: Introductionmentioning

confidence: 99%

Genetic and non-genetic correlates of vitamins K and D

et al. 2007

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Objective: To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a communitybased sample of men and women. Subjects/Methods: A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Results: Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate ¼ 28.8%, Po0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance. Conclusions: Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

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Genetic Contribution to Bone Metabolism, Calcium Excretion, and Vitamin D and Parathyroid Hormone Regulation

Cited by 218 publications

References 37 publications

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

Genetic and non-genetic correlates of vitamins K and D

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