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No Evidence for Posttreatment Effects of Vitamin D and Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial.
Calderwood, AH, Baron, JA, Mott, LA, Ahnen, DJ, Bostick, RM, Figueiredo, JC, Passarelli, MN, Rees, JR, Robertson, DJ, Barry, EL
Cancer prevention research (Philadelphia, Pa.). 2019;(5):295-304
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Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D3 against colorectal adenoma recurrence. It is possible vitamin D3 and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence. In this secondary analysis of the observational follow-up phase of the Vitamin D/Calcium Polyp Prevention Study, participants who completed the treatment phase were invited to be followed for one additional surveillance colonoscopy cycle. We evaluated adenoma occurrence risk at surveillance colonoscopy, with a mean of 55 ± 15 months after treatment follow-up, according to randomized treatment with vitamin D versus no vitamin D, calcium versus no calcium, and calcium plus vitamin D versus calcium alone. Secondary outcomes included advanced and multiple adenomas. Among the 1,121 participants with observational follow-up, the relative risk (95% confidence interval, CI) of any adenoma was 1.04 (0.93-1.17) for vitamin D versus no vitamin D; 0.95 (0.84-1.08) for calcium versus no calcium; 1.07 (0.91-1.25) for calcium plus vitamin D versus calcium; and 0.96 (0.81-1.15) for calcium plus vitamin D versus neither. Risks of advanced or multiple adenomas also did not differ by treatment. Our results do not support an association between supplemental calcium and/or vitamin D3 for 3 to 5 years and risk of recurrent colorectal adenoma at an average of 4.6 years after treatment.
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Long-Term Complications in Patients With Hypoparathyroidism Evaluated by Biochemical Findings: A Case-Control Study.
Underbjerg, L, Sikjaer, T, Rejnmark, L
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018;(5):822-831
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Hypoparathyroidism (HypoPT) is associated with an increased risk of various complications, but only few data are available on risk factors. Using a case-control design, we assessed associations between biochemical findings and risk of different complications within a subpopulation of our previously identified Danish patients. We retrieved all biochemical data available on 431 (81% women) patients from the Central Region of Denmark, covering approximately 20% of the Danish population. Average age of patients was 41 years at time of diagnosis. Most patients (88%) had HypoPT due to surgery, mainly due to atoxic goiter and more than 95% were on treatment with calcium supplements and activated vitamin D. On average, time-weighted (tw) plasma levels of ionized calcium (Ca2+tw ) was 1.17 mmol/L (interquartile range [IQR], 1.14 to 1.21 mmol/L) and the calcium-phosphate (CaxPtw ) product was 2.80 mmol2 /L2 (IQR, 2.51 to 3.03 mmol2 /L2 ). High phosphatetw levels were associated with increased mortality and risk of any infections, including infections in the upper airways. A high CaxPtw product was associated with an increased mortality and risk of renal disease. Compared to levels around the lower part of the reference interval, lower Ca2+tw levels were associated with an increased risk of cardiovascular diseases. Mortality and risk of infections, cardiovascular diseases, and renal diseases increased with number of episodes of hypercalcemia and with increased disease duration. Treatment with a relatively high dose of active vitamin D was associated with a decreased mortality and risk of renal diseases and infections. In conclusion, risk of complications in HypoPT is closely associated with disturbances in calcium-phosphate homeostasis. © 2018 American Society for Bone and Mineral Research.
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Role of FGF23 in Pediatric Hypercalciuria.
Moreira Guimarães Penido, MG, de Sousa Tavares, M, Saggie Alon, U
BioMed research international. 2017;:3781525
Abstract
BACKGROUND This study explored the possible role of FGF23 in pediatric hypercalciuria. METHODS Plasma FGF23 was measured in 29 controls and 58 children and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34 after 6 months of treatment (Treated). Hypercalciuric patients also measured serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine calcium, phosphate, and creatinine. RESULTS There were no differences in age, gender, ethnicity, or body mass index either between controls and patients, or between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72 compared with all patients, 58 RU/mL (p = 0.0019). However, whereas FGF23 in Pre-Treated patients, 73 RU/mL, was not different from controls, in Treated patients it was 50 RU/mL, significantly lower than in both controls (p < 0.0001) and Pre-Treated patients (p = 0.02). In all patients, there was a correlation between FGF23 and urinary calcium (r = 0.325; p = 0.0014). Treated patients had significantly lower urinary calcium (p < 0.0001), higher TP/GFR (p < 0.001), and higher serum phosphate (p = 0.007) versus Pre-Treated patients. CONCLUSIONS Pharmacological treatment of hypercalciuric patients resulted in significantly lower urinary calcium excretion, lower serum FGF23, and elevated TP/GFR and serum phosphate concentration, without significant changes in PTH. Further studies are indicated. This trial is registered with Clinical Registration Number RBR 8W27X5.
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Higher Dietary Calcium Intakes Are Associated With Reduced Risks of Fractures, Cardiovascular Events, and Mortality: A Prospective Cohort Study of Older Men and Women.
Khan, B, Nowson, CA, Daly, RM, English, DR, Hodge, AM, Giles, GG, Ebeling, PR
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2015;(10):1758-66
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The aim of this population-based, prospective cohort study was to investigate long-term associations between dietary calcium intake and fractures, non-fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (∼99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD-related deaths (n = 557), cerebrovascular disease-related deaths (n = 139), incident non-fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ∼13 years after baseline. Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all-cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76-0.98, p(trend) = 0.01); for non-fatal CVD and stroke, the OR was 0.84 (95% CI 0.70-0.99, p(trend) = 0.04) and 0.69 (95% CI 0.51-0.93, p(trend) = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54-0.92, p(trend) = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non-fatal CVD, stroke, and all-cause mortality.
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The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.
Lappe, JM, Watson, P, Gilsanz, V, Hangartner, T, Kalkwarf, HJ, Oberfield, S, Shepherd, J, Winer, KK, Zemel, B
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2015;(1):156-64
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Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development.
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25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype.
Jones, KS, Assar, S, Harnpanich, D, Bouillon, R, Lambrechts, D, Prentice, A, Schoenmakers, I
The Journal of clinical endocrinology and metabolism. 2014;(9):3373-81
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CONTEXT There is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D). OBJECTIVE The objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status. PARTICIPANTS Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study. INTERVENTIONS The intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days. MAIN OUTCOME MEASURES 25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured. RESULTS 25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country. CONCLUSIONS 25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.
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Effect of calcium phosphate and vitamin D₃ supplementation on bone remodelling and metabolism of calcium, phosphorus, magnesium and iron.
Trautvetter, U, Neef, N, Leiterer, M, Kiehntopf, M, Kratzsch, J, Jahreis, G
Nutrition journal. 2014;:6
Abstract
BACKGROUND The aim of the present study was to determine the effect of calcium phosphate and/or vitamin D₃ on bone and mineral metabolism. METHODS Sixty omnivorous healthy subjects participated in the double-blind, placebo-controlled parallel designed study. Supplements were tricalcium phosphate (CaP) and cholecalciferol (vitamin D₃). At the beginning of the study (baseline), all subjects documented their normal nutritional habits in a dietary record for three successive days. After baseline, subjects were allocated to three intervention groups: CaP (additional 1 g calcium/d), vitamin D₃ (additional 10 μg/d) and CaP + vitamin D₃. In the first two weeks, all groups consumed placebo bread, and afterwards, for eight weeks, the test bread according to the intervention group. In the last week of each study period (baseline, placebo, after four and eight weeks of intervention), a faecal (three days) and a urine (24 h) collection and a fasting blood sampling took place. Calcium, phosphorus, magnesium and iron were determined in faeces, urine and blood. Bone formation and resorption markers were analysed in blood and urine. RESULTS After four and eight weeks, CaP and CaP + vitamin D₃ supplementations increased faecal excretion of calcium and phosphorus significantly compared to placebo. Due to the vitamin D₃ supplementations (vitamin D₃, CaP + vitamin D₃), the plasma 25-(OH)D concentration significantly increased after eight weeks compared to placebo. The additional application of CaP led to a significant increase of the 25-(OH)D concentration already after four weeks. Bone resorption and bone formation markers were not influenced by any intervention. CONCLUSIONS Supplementation with daily 10 μg vitamin D₃ significantly increases plasma 25-(OH)D concentration. The combination with daily 1 g calcium (as CaP) has a further increasing effect on the 25-(OH)D concentration. Both CaP alone and in combination with vitamin D₃ have no beneficial effect on bone remodelling markers and on the metabolism of calcium, phosphorus, magnesium and iron. TRIAL REGISTRATION NCT01297023.
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Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium.
Mangano, KM, Walsh, SJ, Kenny, AM, Insogna, KL, Kerstetter, JE
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;(2):500-6
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High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005-2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38-0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.
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Calcium absorption response to cholecalciferol supplementation in hemodialysis.
Armas, LA, Zena, M, Lund, R, Heaney, RP
Clinical journal of the American Society of Nephrology : CJASN. 2013;(6):1003-8
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BACKGROUND AND OBJECTIVES Recent understanding of extrarenal production of calcitriol has led to the use of more vitamin D supplementation in CKD populations. This paper reports the effect of cholecalciferol supplementation on calcium absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Paired calcium absorption tests were done before and after 12-13 weeks of 20,000 IU weekly cholecalciferol supplementation in 30 participants with stage 5 CKD on hemodialysis. The study was conducted from April to December of 2011. Calcium absorption was tested with a standardized meal containing 300 mg calcium carbonate intrinsically labeled with (45)Ca; 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured. RESULTS 25-Hydroxyvitamin D rose from 14.2 ng/ml (11.5-18.5) at baseline to 49.3 ng/ml (42.3-58.1) at the end of the study (P<0.001). 1,25-Dihydroxyvitamin D rose from 15.1 (10.5-18.8) pg/ml at baseline to 20.5 (17.0-24.7) pg/ml at the end of the study (P<0.001). The median baseline calcium absorption was 12% (7%-17%) and 12% (7%-16%) at the end of study. CONCLUSIONS Patients with stage 5 CKD on hemodialysis had very low calcium absorption values at baseline, and cholecalciferol supplementation that raised 25(OH)D levels to 50 ng/ml had no effect on calcium absorption.
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Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: a prospective study.
Krishnamoorthy, G, Nair, R, Sundar, U, Kini, P, Shrivastava, M
Neurology India. 2010;(2):213-9
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BACKGROUND Long-term therapy with antiepileptic drugs (AED) may be associated with increased total serum alkaline phosphatase (ALP) levels and reduced serum calcium, inorganic phosphorous, and vitamin D levels. These adverse biochemical alterations have an adverse effect on bone health. OBJECTIVE To determine (a) onset of derangements in serum total ALP and its isoenzymes (liver, bone), calcium and 25-hydroxy vitamin D (25-OHD) concentrations after initiation of treatment with phenytoin or valproic acid monotherapy and (b) the effect of simultaneous supplementation with calcium and 25-OHD at recommended daily allowance (RDA) dosage, on these biochemical parameters. MATERIALS AND METHODS Study was a prospective, case-controlled study in adults. Serum biochemical parameters were estimated at baseline, 30, 60, and 90 days of starting AED treatment in the study subjects: Groups--A (only calcium supplementation) and Group B (both calcium and 25-OHD supplementation). STATISTICAL ANALYSIS Mean+/-SD, and students' paired t test (between groups A and B) unpaired students' t test (drug-wise). RESULTS At 60 days of AED therapy Group A showed a significant increase in serum total ALP (78.83+/-11.04 to 101.75 +/- 9.56 IU/l) (P < 0.001), ALP-liver isoenzyme, (41.97+/- 10.81 to 68.83 +/-7.81 IU/L) (P < 0.001), significant decrease in calcium (9.30 +/- 0.36 to 8.80 +/- 0.38 mg%) (P < 0.001), ALP-bone isoenyzme (36.84 +/- 5.01 to 32.92 +/- 6.46 IU/L) (P < 0.001), and a significant decrease in 25-OHD (25.19 +/- 5.98 to 19.76 +/- 5.35 ng/ml) (P < 0.001) at 90 days. In contrast Group B, at 60 days, showed a significant decrease in serum total ALP (81.92 +/- 19.63 to 54.77. +/- 11.53 IU/L) (P < 0.0001), ALP-liver isoenzyme (48.01. +/- 13.53 to 28.12. +/- 5.88 IU/L) (P < 0.0001), significant increase in calcium ((9.24 +/- 0.31 to 9.93 +/- 0.26 mg%) (P < 0.001) and ALP-bone isoenzyme levels (33.93 +/- 12.2 to 26.25 +/- 8.23 IU/L). In Group B, 25-OHD levels showed a significant increase at 90 days (24.36 +/- 3.42 to 31.53 +/- 327 ng/ml) (P < 0.0001). CONCLUSION Biochemical derangements in calcium metabolism involving the bone are seen by 60 days after starting AED monotherapy, indicating predisposition to development of osteomalacia in these patients. This is preventable by simultaneous oral supplementation with calcium and 25-OHD.