Fractional Calcium Absorption Research Articles

Running exercise with and without calcium supplementation from tuna bone reduced bone impairment caused by low calcium intake in young adult rats

Inadequate calcium intake during childhood and adolescence is detrimental to bone metabolism. Here, we postulated that calcium supplement prepared from tuna bone with tuna head oil should benefit for skeletal development than CaCO3. Forty female 4-week-old rats were divided into calcium-replete diet (0.55% w/w, S1, n = 8) and low-calcium groups (0.15% w/w for 2 weeks; L; n = 32). Then L were subdivided into 4 groups (8/group), i.e., remained on L, L + tuna bone (S2), S2 + tuna head oil + 25(OH)D3 and S2 + 25(OH)D3. Bone specimens were collected at week 9. We found that 2 weeks on low calcium diet led to low bone mineral density (BMD), reduced mineral content, and impaired mechanical properties in young growing rats. Intestinal fractional calcium absorption also increased, presumably resulting from higher plasma 1,25(OH)2D3 (1.712 ± 0.158 in L vs. 1.214 ± 0.105 nM in S1, P < 0.05). Four-week calcium supplementation from tuna bone further increased calcium absorption efficacy, which later returned to the basal level by week 9. Calcium supplementation successfully restored BMD, bone strength and microstructure. However, 25(OH)D3 + tuna head oil + tuna bone showed no additive effect. Voluntary running also effectively prevented bone defects. In conclusion, both tuna bone calcium supplementation and exercise are effective interventions for mitigating calcium-deficient bone loss.

High Fiber Diets Slow Bone Turnover in Young Men but Have No Effect on Efficiency of Intestinal Calcium Absorption

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Calcium Absorption from Food Products: Food Matrix Effects.

This article reviews physicochemical aspects of calcium absorption from foods. Notable differences are observed between different food products in relation to calcium absorption, which range from <10% to >50% of calcium in the foods. These differences can be related to the interactions of calcium with other food components in the food matrix, which are affected by various factors, including fermentation, and how these are affected by the conditions encountered in the gastrointestinal tract. Calcium absorption in the intestine requires calcium to be in an ionized form. The low pH in the stomach is critical for solubilization and ionization of calcium salts present in foods, although calcium oxalate complexes remain insoluble and thus poorly absorbable. In addition, the rate of gastric transit can strongly affect fractional absorption of calcium and a phased release of calcium into the intestine, resulting in higher absorption levels. Dairy products are the main natural sources of dietary calcium in many diets worldwide, which is attributable to their ability to provide high levels of absorbable calcium in a single serving. For calcium from other food products, lower levels of absorbable calcium can limit contributions to bodily calcium requirements.

Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial.

The adverse skeletal effects of Roux-en-Y gastric bypass (RYGB) are partly caused by intestinal calcium absorption decline. Prebiotics, such as soluble corn fiber (SCF), augment colonic calcium absorption in healthy individuals. We tested the effects of SCF on fractional calcium absorption (FCA), biochemical parameters, and the fecal microbiome in a post-RYGB population. Randomized, double-blind, placebo-controlled trial of 20 postmenopausal women with history of RYGB a mean 5 years prior; a 2-month course of 20 g/day SCF or maltodextrin placebo was taken orally. The main outcome measure was between-group difference in absolute change in FCA (primary outcome) and was measured with a gold standard dual stable isotope method. Other measures included tolerability, adherence, serum calciotropic hormones and bone turnover markers, and fecal microbial composition via 16S rRNA gene sequencing. Mean FCA ± SD at baseline was low at 5.5 ± 5.1%. Comparing SCF to placebo, there was no between-group difference in mean (95% CI) change in FCA (+3.4 [-6.7, +13.6]%), nor in calciotropic hormones or bone turnover markers. The SCF group had a wider variation in FCA change than placebo (SD 13.4% vs 7.0%). Those with greater change in microbial composition following SCF treatment had greater increase in FCA (r2 = 0.72, P = 0.05). SCF adherence was high, and gastrointestinal symptoms were similar between groups. No between-group differences were observed in changes in FCA or calciotropic hormones, but wide CIs suggest a variable impact of SCF that may be due to the degree of gut microbiome alteration. Daily SCF consumption was well tolerated. Larger and longer-term studies are warranted.

Excessive salt consumption causes systemic calcium mishandling and worsens microarchitecture and strength of long bones in rats

Excessive salt intake has been associated with the development of non-communicable diseases, including hypertension with several cardiovascular consequences. Although the detrimental effects of high salt on the skeleton have been reported, longitudinal assessment of calcium balance together with changes in bone microarchitecture and strength under salt loading has not been fully demonstrated. To address these unanswered issues, male Sprague–Dawley rats were fed normal salt diet (NSD; 0.8% NaCl) or high salt diet (HSD; 8% NaCl) for 5 months. Elevation of blood pressure, cardiac hypertrophy and glomerular deterioration were observed in HSD, thus validating the model. The balance studies were performed to monitor calcium input and output upon HSD challenge. The HSD-induced increase in calcium losses in urine and feces together with reduced fractional calcium absorption led to a decrease in calcium retention. With these calcium imbalances, we therefore examined microstructural changes of long bones of the hind limbs. Using the synchrotron radiation x-ray tomographic microscopy, we showed that trabecular structure of tibia and femur of HSD displayed a marked increase in porosity. Consistently, the volumetric micro-computed tomography also demonstrated a significant decrease in trabecular bone mineral density with expansion of endosteal perimeter in the tibia. Interestingly, bone histomorphometric analyses indicated that salt loading caused an increase in osteoclast number together with decreases in osteoblast number and osteoid volume. This uncoupling process of bone remodeling in HSD might underlie an accelerated bone loss and bone structural changes. In conclusion, long-term excessive salt consumption leads to impairment of skeletal mass and integrity possibly through negative calcium balance.

Metabolic Calcium Balance in Rats with Chronic Renal Failure Assessed Using 42Ca Tracer

Objective: This study's objective is to explore the effect of venous calcium (Ca) load on Ca metabolism using an isotope tracer in both healthy rats and rats with chronic renal failure (CRF). Materials and Methods: The methods included inducing CRF by feeding rats with food that containing 0.75% adenine. Both the rats in the control and CRF group received an intravenous injection of 100 mg/kg CaCl2 mixed with 0.5 mg/kg 42Ca for over 2 minutes in order to induce hypercalcemia. Blood samples, urine, and feces were collected for Ca kinetics and metabolism testing before and 24 hours after the injection. Results: Peak blood Ca levels were presented at 5 minutes in both groups but returned to baseline levels differently: within 3 hours in the CRF group and 1 hour in the control group. 24-hour hypercalciuria and a higher weight-corrected fecal Ca loss were consistently detected in the CRF rats before and after the injection, along with a decrease in the percent fractional Ca absorption and true fractional calcium absorption compared to the control group. The increased fecal Ca in the CRF rats primarily resulted from changes in decreased absorption rate, which indirectly lead to an increase in endogenous fecal Ca (EFC). Body weightcorrected EFC levels in the CRF group were significantly higher than those in the control group (207.58 ± 107.18 mg/kg/day vs. 62.44 ± 20.49 mg/kg/day). In addition, EFC was 22.6% and 26.02% of the total fecal Ca in the CRF group and the control group. Conclusion: These results may be useful in the evaluation of calcium metabolism and may have important implications for stable isotopes that are widely used in exploring calcification studies in the CRF.

Supplemental calcium intake in the aging individual: implications on skeletal and cardiovascular health.

Adequate calcium intake during childhood is necessary to achieve optimal peak bone mass and this has the potential by increasing bone reserves, to modulate the rate of age-associated bone loss. However, data regarding the efficacy of calcium obtained either through the diet or in the form of medicinal supplementation, for prevention of bone loss and osteoporotic fractures in the elderly is conflicting. Calcium alone is unlikely to be of benefit for this purpose though the co-administration of calcium and vitamin D may have modest fracture risk benefits. Supplemental calcium with or without vitamin D has recently come into the spotlight after the publication of the findings from a controversial randomized controlled trial that associated calcium supplementation with an increased risk of myocardial infarction. Since then, multiple studies have explored this potential link. The data remains conflicting and the potential mechanistic link if any exists, remains elusive. This review examines the relationship between supplemental calcium intake and skeletal and cardiovascular health in the aging individual through an appraisal of studies done on the subject in the last three decades. It also briefly details some of the studies evaluating fractional absorption of calcium in the elderly and the rationale behind the current recommended dietary allowances of calcium.

Dexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women

Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40mg), or placebo daily for 26 weeks. We measured plasma levelsof procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n= 30). Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293.

The influence of dietary fat and intestinal pH on calcium bioaccessibility: an in vitro study.

In vivo studies measuring true fractional calcium (Ca) absorption have shown that dietary fat is a significant predictor of absorption and is influenced by luminal pH levels. However, whether changes in Ca bioaccessibility (CaB) can explain the effects on absorption has not been examined. In the current study, we examined two high fat diets enriched in either monounsaturated fatty acids or saturated fatty acids (SFA), and a low-fat diet (LFD), each with 50 mg Ca, and measured CaB at different intestinal regions during normal acidic or higher (pH = 7) gastrointestinal conditions using an in vitro gastrointestinal model. During normal pH conditions in the jejunum, there was an interaction between diet and time for CaB (P < 0.02), and CaB during the SFA diet was higher than LFD (P = 0.05). CaB was reduced by 90 ± 3% during higher compared with normal pH under all dietary conditions (P < 0.001). These findings indicate that fat intake, especially SFA enriched, is associated with a greater CaB in the jejunum, and may explain the higher Ca absorption in previous studies. In addition, the marked reduction in CaB under higher pH conditions could have implications in persons taking medications to reduce gastric acid.

Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis

SummaryIntestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH)2D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine.IntroductionTo assess the effects of vitamin D3 compounds on intestinal FCA and calcium-regulating hormones in post-menopausal osteoporosis, a randomized open-label prospective study was conducted.MethodsForty eligible patients were allocated randomly into four groups: eldecalcitol (ELD; 0.75 μg/day), 1α hydroxyl calcidiol (ALF; 1 μg/day), plain vitamin D3 (800 IU/day), and control. Before and after the 4-week treatment, intestinal FCA was estimated by using a double isotope method, and serum concentrations of calcium-regulating hormones and a bone turnover marker were measured.ResultsThe baseline FCA value of the participants was 21.5 ± 7.9% (mean ± SD) and was significantly correlated with serum 1,25(OH)2D (calcitriol) concentration. After the treatment, the FCA significantly increased by 59.5% (95% CI, 41.6 to 77.4%) in the ELD group and by 45.9% (27.9 to 63.8%) in the ALF group, whereas no significant change in the plain vitamin D3 group was found. Unlike the baseline FCA, post-treatment FCA exhibited no significant correlation with serum calcitriol concentration. Parathyroid hormone levels were suppressed by ALF and plain vitamin D3 but were sustained in the ELD and control groups. Serum calcitriol tended to be suppressed by ELD, whereas plain vitamin D3 treatment increased both serum 25(OH)D and calcitriol concentrations.ConclusionThese findings suggest that oral administration of vitamin D3 analogues (ALF and ELD) stimulates FCA but plain vitamin D3 does not. Those effects of vitamin D3 compounds on FCA were independent of serum calcitriol concentration, suggesting that ALF and ELD may directly stimulate intestinal vitamin D receptors.

Evidence of disordered calcium metabolism in adolescent girls with type 1 diabetes: An observational study using a dual-stable calcium isotope technique

Type 1 diabetes (T1D) is associated with skeletal abnormalities including low bone density and increased fracture risk. The pathophysiology underlying T1D related skeletal fragility remains unknown. The objective of this study was to use a dual-stable calcium isotope method to investigate the effects of T1D on calcium absorption and estimated calcium retention in adolescent females. Twenty adolescent females with T1D were admitted for a 24-h calcium absorption study using oral (44Ca) and intravenous (42Ca) stable isotopes for determination of percent gastrointestinal calcium absorption and estimated calcium retention. Five out of twenty participants were found to have negative estimated calcium retention. Participants with negative calcium retention had greater urinary calcium excretion [202mg/d (IQR: 178–213)] compared to those with positive calcium retention [101.5mg/d (IQR: 82–122)], p=0.01, but similar calcium intake and percent calcium absorption. With the exception of one outlier, 24-h urine calcium was significantly associated with hemoglobin A1c (Pearson's r=0.55, p=0.02). 50% of participants consumed less than the RDA for calcium; fractional calcium absorption was inversely correlated with calcium intake in participants not meeting the RDA (Spearman's rho −0.65, p=0.04). In conclusion, one-quarter of adolescent girls with T1D were found to have negative estimated calcium retention at a time when bone mineral accrual should be ongoing. This appeared to be the result of excess urinary calcium excretion as opposed to diminished gastrointestinal calcium absorption. Insufficient calcium availability for bone deposition during adolescence could impair bone mineral accrual and contribute to skeletal fragility.Trial registered: ClinicalTrials.gov Reg No. NCT03156179

Hypocalciuria as a Predictor of Reduced Intestinal Calcium Absorption.

Impaired intestinal calcium absorption contributes to osteoporosis, but its measurement is limited to research settings. We hypothesized that 24-hour urine calcium (24HUC) values could diagnose low fractional calcium absorption (FCA). We performed a post hoc analysis of clinical trial data to determine whether 24HUC predicted low FCA compared with the gold standard dual calcium isotope method. Two hundred thirty postmenopausal women <75 years old without osteoporosis underwent 445 FCA measurements using calcium isotopes (8 mg of oral 44Ca, 3 mg of intravenous 42Ca) and a 24-hour inpatient urine collection at 0 and 12 months. We determined subjects’ total calcium intake via review of food diaries and supplements. Net calcium absorption (NCA) was total calcium intake × FCA. NCA and 24HUC values demonstrated a positive correlation (r = 0.34; 95% confidence interval, 0.25 to 0.42; P < 0.001). We calculated sensitivity, specificity, positive (PPV) and negative predictive value (NPV) for the ability of 24HUC thresholds to predict calcium malabsorption. When low calcium absorption was defined as <120 mg/d, a 24HUC value <150 mg demonstrated 65% sensitivity, 67% specificity, 31% PPV, and 89% NPV. When calcium malabsorption was defined as <100 mg/d, a 24HUC value <150 mg demonstrated 72% sensitivity, 65% specificity, 22% PPV, and 94% NPV. A 24HUC value <150 mg demonstrated a high NPV for calcium malabsorption. We suggest that 24HUC levels can exclude calcium malabsorption in postmenopausal women.

Habitual dietary calcium intakes and calcium metabolism in healthy adults Chinese: a systematic review and meta-analysis.

To investigate the metabolic differences of calcium requirements between Chinese and Westerners, we examined systematically the characteristics of calcium metabolism in Chinese adults with habitual dietary calcium intakes. We searched PubMed, Cochrane Library, SinoMed, and National Index to Chinese Newspapers & Periodicals, from inception to March 17, 2015, as well as the bibliographies of any relevant papers and journals, for trials assessing calcium metabolism in healthy Chinese adults within 18-60 years of age on the typical Chinese diet. We extracted a standardized dataset from metabolic studies that reported intake, retention, urinary excretion, faecal excretion and/or fractional absorption of calcium. We pooled data with a random effects meta-analysis. Of 2,046 citations identified by the search strategy, 12 studies (comprising 137 participants, 13 aggregate data deriving from 257 individual data) met the inclusion criteria. Metabolic data with self-chosen or typical Chinese diets were analyzed. Mean daily intakes of calcium ranged between 288 and 948 mg. Mean calcium retentions of each study were between 13 and 294 mg/d. The overall pooled value for dietary intake, urinary excretion, faecal excretion, retention and fractional absorption of calcium were 583 mg/d, 117 mg/d, 381 mg/d, 72 mg/d and 33.3%. Dietary calcium intake and faecal calcium excretion explained almost 85% of the heterogeneity of calcium retention. Chinese adults could maintain a positive calcium balance with plant-based diets at calcium intakes as low as 300 mg/d through increasing fractional calcium absorption and decreasing calcium excretion in urine and faeces.

High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice

Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects.

Flesh yield of small indigenous fishes from the River Padma, Rajshahi, Bangladesh

Abstract not availableBangladesh J. Zool. 43(1): 141-144, 2015

Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial.

Experts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health. To compare the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density, Timed Up and Go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency. This randomized, double-blind, placebo-controlled clinical trial was conducted at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013, and the final visit was completed on August 8, 2014. A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied. Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL. Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed Up and Go and five sit-to-stand tests, functional status (Health Assessment Questionnaire), and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of P values to control for the false discovery rate. After baseline absorption was controlled for, calcium absorption increased 1% (10 mg/d) in the high-dose arm but decreased 2% in the low-dose arm (P = .005 vs high-dose arm) and 1.3% in the placebo arm (P = .03 vs high-dose arm). We found no between-arm changes in spine, mean total-hip, mean femoral neck, or total-body bone mineral density, trabecular bone score, muscle mass, and Timed Up and Go or five sit-to-stand test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity, or functional status. High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass, or falls. We found no data to support experts' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL. clinicaltrials.gov Identifier: NCT00933244.

Can serum isotope levels accurately measure intestinal calcium absorption compared to gold-standard methods?

BackgroundLow fractional calcium absorption (FCA) contributes to osteoporosis but is not measured clinically, as the gold-standard method requires administration of two calcium tracers and a subsequent 24-h urine collection. We evaluated alternate methods to measure FCA, compared to the gold standard method.MethodsWe administered two stable calcium isotope tracers (~8 mg oral 44Ca and ~3 mg intravenous 42Ca) with breakfast to 20 fasting post-menopausal women (Cohort 1) 59 ± 7 years old with vitamin D insufficiency. We measured subsequent calcium isotope concentrations in 24-h urine samples and serum collected 1, 3 and 5 h post tracer administration during an inpatient research stay. We assessed the candidate serum estimates in a second cohort of 9 women with similar characteristics. Methods of measuring FCA were compared using correlation coefficients and Bland-Altman tests.ResultsFCA estimated from a 3-h serum sample correlated highest with the levels from the 24-h urine collection (ρ 0.78, p < 0.001), but explained only 58 % of the variance in FCA. The total variance explained by 3-h estimates improved to 61 % with incorporation of glomerular filtration rate (GFR). FCA estimates from the 3-h serum measurement were assessed in a second group of nine women (Cohort 2) 60 ± 7 years old. In this cohort, however, FCA estimated by 3-h serum isotope levels did not correlate with gold-standard FCA measurements, whether determined with (ρ 0.02, p = 0.97) or without GFR values (ρ 0.03, p = 0.93). By contrast, FCA in Cohort 2 correlated best with 5-h serum isotope levels (ρ 0.75, p = 0.02).ConclusionsWe conclude that serum isotope levels correlate with true fractional calcium absorption, but do not reliably estimate FCA when analyzed using Bland-Altman tests, compared to gold-standard methods.Trial registrationClinicalTrials.gov.Identifier: NCT00933244

Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction

Low calcium absorption is associated with low bone mass and fracture. In this study, we use gold standard methods of fractional calcium absorption (FCA) to determine whether polymorphisms of intestinal receptors, vitamin D receptor (VDR) and estrogen receptor α (ESR1), influence the response to energy restriction. Fractional calcium absorption was measured using dual stable isotopes (42Ca and 43Ca) in women given adequate calcium and vitamin D and examined at baseline and after 6weeks of energy restriction or no intervention. After genotyping, the relationship between VDR and ESR1 genotypes/haplotypes and FCA response was assessed using several genetic models. One-hundred and sixty-eight women (53±11years of age) were included in this analysis. The ESR1 polymorphisms, PvuII and XbaI and VDR polymorphisms (TaqI, ApaI) did not significantly influence FCA. The BB genotype of the VDR polymorphism, BsmI, was associated with a greater decrease in FCA than the Bb/bb genotype. Multiple linear regression showed that the BsmI polymorphism or the VDR haplotype, BAt, in addition to changes in weight and vitamin D intake explained ~16% of the variation in changes in FCA. In conclusion, the reduction in calcium absorption due to energy restriction is greatest for those with the BB genotype. Previous candidate gene studies show that VDR polymorphisms are associated with higher risk for osteoporosis, and the current study supports the notion that the BsmI polymorphism in intestinal VDR may be contributing to alterations in bone health.

Vitamin D Status Is Positively Associated with Calcium Absorption among Postmenopausal Thai Women with Low Calcium Intakes ,

Few data exist on the ability of postmenopausal women to absorb calcium from diets habitually low in calcium. The objective of this study was to evaluate fractional calcium absorption from a green leafy vegetable vs. milk in relation to vitamin D status. We measured fractional calcium absorption from both a dairy- and plant-based source in 19 postmenopausal Thai women (aged 52-63 y) with low calcium consumption (350 ± 207 mg/d) in relation to serum parathyroid hormone (PTH) and serum 25-hydroxyvitamin D [25(OH)D]. Fractional calcium absorption was measured using a triple stable calcium isotope method based on isotope recovery in a 28-h urine collection. Two extrinsically labeled test meals were ingested in random order: a green leafy vegetable (cassia) ingested along with ⁴³Ca or a glass of milk containing ⁴⁴Ca. Women received intravenous ⁴²Ca with the first test meal. In 19 postmenopausal women studied (mean age, 56.9 ± 3.4 y), ~95% were 25(OH)D sufficient (≥20 μg/L). Serum 25(OH)D status was positively correlated with fractional absorption from both cassia (P = 0.05, R² = 0.21) and milk (P = 0.03, R² = 0.26). Fractional calcium absorption from cassia was significantly lower than that measured from milk (42.6% ± 12.3% vs. 47.8% ± 12.8%, P = 0.03), but true calcium absorption did not significantly differ (120 ± 35 mg/d vs. 135 ± 36 mg/d). Serum PTH was significantly inversely associated with serum 25(OH)D (P = 0.006, R² = 0.37) even though PTH was not elevated (>65 pg/mL). These findings suggest that vitamin D status is an important determinant of calcium absorption among Thai women with low calcium intakes, and cassia may be a readily available source of calcium in this population. Furthermore, these data indicate that serum 25(OH)D concentrations may affect PTH elevation in postmenopausal women with low calcium intakes.

Diet, gut microbiome, and bone health.

Interactions between the environment, the gut microbiome, and host characteristics that influence bone health are beginning to be explored. This is the first area where functional benefits from diet-induced changes in the gut microbiome have been reported for healthy people. Several prebiotics that reach the lower intestine have resulted in an altered gut microbiome that is thought to enhance fermentation of the fibers to produce short-chain fatty acids. These changes are positively correlated with increases in fractional calcium absorption in adolescents and with increases in measures of bone density and strength in animal models. New methodologies are available to explore mechanisms and to refine intervention strategies.