Improve Calcium Balance Research Articles

Are Probiotics the New Calcium and Vitamin D for Bone Health?

Calcium and vitamin D supplementation is recommended for patients at high risk of fracture and/or for those receiving pharmacological osteoporosis treatments. Probiotics are micro-organisms conferring a health benefit on the host when administered in adequate amounts, likely by influencing gut microbiota (GM) composition and/or function. GM has been shown to influence various determinants of bone health. In animal models, probiotics prevent bone loss associated with estrogen deficiency, diabetes, or glucocorticoid treatments, by modulating both bone resorption by osteoclasts and bone formation by osteoblast. In humans, they interfere with 25-hydroxyvitamin D levels, and calcium intake and absorption, and slightly decrease bone loss in elderly postmenopausal women, in a quite similar magnitude as observed with calcium ± vitamin D supplements. A dietary source of probiotics is fermented dairy products which can improve calcium balance, prevent secondary hyperparathyroidism, and attenuate age-related increase of bone resorption and bone loss. Additional studies are required to determine whether probiotics or any other interventions targeting GM and its metabolites may be adjuvant treatment to calcium and vitamin D or anti-osteoporotic drugs in the general management of patients with bone fragility.

A Naringin- and Icariin-Contained Herbal Formula, Gushukang, Ameliorated Aged Osteoporosis of Aged Mice with High Calcium Intake.

Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis and showed osteoprotective effect in ovariectomized rodent animals and regulatory action on calcium transporters. This study aimed to determine if GSK could ameliorate aged osteoporosis by modulating serum level of calciotropic hormones and improving calcium balance. 18-month-old male mice were orally administered with either GSK (0.38[Formula: see text]g/kg body weight) or calcitriol (1[Formula: see text][Formula: see text]g/kg body weight) combined with high calcium diet (HCD, 1.2% Ca) for 60 days. The aged mice fed with normal calcium diet (NCD, 0.6% Ca) were a negative control. Trabecular bone and cortical bone properties as well as calcium balance were determined. Treatment with GSK significantly increased 25(OH)D and 1,25-(OH)2D levels in serum, moreover, it markedly attenuated trabecular bone micro-architectural deteriorations and elevated trabecular bone mass as well as strengthened cortical bone mechanical properties shown by the increase in maximal bending load and elastic modulus. Calcium balance, including urinary Ca excretion, fecal Ca level and net calcium retention, was remarkably improved by GSK, which up-regulated TRPV6 expression in duodenum and TRPV5 expression in kidney and down-regulated claudin-14 expression in duodenum and kidney. Additionally, 1-OHase and 24-OHase expression was significantly decreased (vs. NCD group) and increased (vs. HCD group), respectively, in kidney of GSK- and calcitriol-treated mice. Taken together, this study demonstrated the ameliorative effects of Gushukang on aged osteoporosis by effectively stimulating vitamin D production and improving calcium balance of aged mice with high dietary calcium supplement.

Protective Effects of Ligustroflavone, an Active Compound from Ligustrum lucidum, on Diabetes-Induced Osteoporosis in Mice: A Potential Candidate as Calcium-Sensing Receptor Antagonist.

Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.

Effects of probiotics, prebiotics, and synbiotics on mineral metabolism in ovariectomized rats — impact of bacterial mass, intestinal absorptive area and reduction of bone turn-over

BackgroundDefined prebiotics were shown to improve calcium balance and diminish bone loss. However, the effect of their combination with probiotics on gut ecology and bone metabolism has not yet been studied. We investigated whether the combination of a probiotic with a defined microbial strain results in improved bone mineralization, and whether this effect is associated with changes in gut ecology. MethodsEighty ovariectomized adult rats were allocated to five groups: group 1, sham-operated (SHAM); group 2–5, ovariectomized (OVX). Semipurified diets containing 0.7% calcium and 0.5% phosphorus were fed for 16weeks, group 1 and group 2 got no supplements, group 3 (PRO) was supplemented with a potential probiotic (Lactobacillus acidophilus NCC90), group 4 (PRE) with prebiotics (oligofructose+acacia gum) and group 5 (SYN) with synbiotics (probiotics+prebiotics). ResultsOvariectomy increased body weight and reduced bone weight, content of calcium, phosphorus and ash of bone, bone alkaline phosphatase (BAP), and bone structure. This was indicated by lower trabecular bone area, trabecular perimeter, and connectivity but higher epiphyseal breadth. Ovariectomy elevated the jejunal pH. The probiotic alone did not significantly affect bone mineralization and gut ecology. Rats on prebiotics had significantly higher amounts of cecal contents and lower pH in cecal and colonic contents. Their calcium balance tended to be increased (p<0.1). Synbiotics reduced pH in different intestinal segments, significantly in cecum. They stimulated most the colonic absorption surface as indicated by colon weight. Only feeding synbiotics significantly prevented OVX-induced loss of calcium content in lumbar vertebrae (mg) with final values (mean±SD) of 44.44±2.94 (SHAM), 41.20±4.59 (OVX), 41.63±3.78 (PRO), 43.42±3.07 (PRE), and 44.68±2.28 (SYN). This effect was associated with higher counts of bifidobacteria in the short-term and Bacteroides in the long-term, and with a tendency for lower BAP with 128.7±28.5U/L vs. 155.3±28.1U/L in OVX (p<0.1). ConclusionSYN exerted a synergistic effect on bone mineralization, presumably due to changes in gut microbiota and ecology associated with large bowel digesta weight (most likely reflecting microbial mass) and with large bowel weight (reflecting absorptive area), while bone turnover tended to be reduced as indicated by BAP.

Eldecalcitol, a vitamin D analog, reduces bone turnover and increases trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys

Vitamin D insufficiency is common in elderly people worldwide, and intake of supplementary calcium and vitamin D is recommended to those with a high risk of fracture. Several clinical studies and meta-analyses have shown that calcium and vitamin D supplementation reduces osteoporotic fractures, and a strong correlation exists between vitamin D status and fracture risk. Vitamin D supplementations improve calcium balance in the body; however, it remains unclear whether vitamin D directly affects bone metabolism. Recently, eldecalcitol (ELD), an active form of vitamin D analog, has been approved for the treatment of osteoporosis in Japan. A 3-year clinical trial showed ELD treatment increased lumbar spine bone mineral density (BMD) and reduced fracture risk in patients with osteoporosis. To evaluate the mechanism of ELD action in bone remodeling, ovariectomized cynomolgus monkeys were treated with 0.1 or 0.3μg/day of ELD for 6months. This treatment increased lumbar BMD by 4.4% and 10.2%, respectively, and suppressed ovariectomy-induced increases in bone turnover markers compared to OVX-vehicle control. Histomorphometric analysis of bone revealed that both bone formation parameters and bone resorption parameters in the trabecular bone of the lumbar vertebrae were suppressed by ELD treatment. ELD treatment also improved biomechanical properties of the lumbar vertebrae and the femoral neck in the ovariectomized cynomolgus monkeys. These results indicate that, in a bone-remodeling animal model, ELD increases BMD and improves bone biomechanical properties by normalizing bone turnover. Therefore, ELD has a direct and potentially beneficial effect on bone metabolism.

Calcium and caffeine interaction in increased calcium balance in ovariectomized rats

OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40) were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day). The animals were kept in individuals metabolic cages at a temperature of 24°±2ºC, light/dark cycles of 12/12 hours, and deionized water available ad libitum. On the 8th week of the experiment, food consumption was measured and 24-hour urine and 4-day feces were collected to determine calcium balance [Balance=Ca intake-(Urinary Ca+Fecal Ca)]. RESULTS: Animals with adequate calcium intake presented higher balances and rates of calcium absorption and retention (p&lt;0.05) than those with inadequate calcium intake, regardless of caffeine intake (p&lt;0.05). Caffeine intake did not affect urinary calcium excretion but increased balance (p&lt;0.05) in the groups with adequate calcium intake. CONCLUSION: Adequate calcium intake attenuated the negative effects of estrogen deficiency and improved calcium balance even in the presence of caffeine.

Treatment of Calcium and Vitamin D Deficiency in HIV-Positive Men on Tenofovir-Containing Antiretrovial Therapy

Background: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate–containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. Objective: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. Methods: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. Results: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. Conclusion: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency.

In‐season calcium‐spray formulations improve calcium balance and fruit quality traits of peach

AbstractExperiments to evaluate the effect of in‐season calcium (Ca) sprays on late‐season peach (Prunus persica L. Batsch cv. Calrico) were carried out for a 2‐year period. Calcium formulations (0.5% and 1.0% in 2008 and only 0.5% tested in 2009) supplied either as CaCl2 or Ca propionate in combination with two or three adjuvants (0.05% of the nonionic surfactants Tween 20 and Break Thru, and 0.5% carboxymethylcellulose, CMC) were sprayed four to five times over the growing season. Peach mesocarp and endocarp Ca concentrations were determined on a 15‐day basis from the beginning of May until the end of June. Further tissue analyses were performed at harvest. A decreasing trend in fruit Ca concentrations over the growing season was always observed regardless of the Ca treatments. Both in 2008 and 2009, significant tissue Ca increments associated with the application of Ca‐containing sprays in combination with adjuvants were only observed in June, which may be coincident with the period of pit hardening. In 2008, both at harvest and after cold storage, the total soluble‐solids concentration (° Brix) of fruits supplied with Ca propionate (0.5% and 1.0% Ca) was always lower as compared to the rest of treatments. The application of multiple Ca‐containing sprays increased firmness at harvest and after cold storage, especially when CaCl2 was the active ingredient used. Supplying the adjuvants Tween 20 and CMC increased fruit acidity both at harvest and after cold storage. Evaluation of the development of physiological disorders after cold storage (2 weeks at 0°C) indicated a lower susceptibility of Ca‐treated fruits to internal browning. Fruits treated with multiple CaCl2‐, CMC‐, and Break Thru®‐containing sprays during the growing season were significantly less prone to the development of chilling injuries as compared to untreated peaches.

PTH analogues and osteoporotic fractures

Importance of the field: At present there are two parathyroid hormone (PTH) analogues (PTH 1 – 34 and PTH 1 – 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 – 34 and PTH 1 – 84) and in men (PTH 1 – 34 only) who are at increased risk of having a fracture.Areas covered in this review: The efficacy and safety of PTH 1 – 34 and PTH 1 – 84 in the management of osteoporosis is evaluated by reviewing published literature and presentations from scientific meetings through to 2010.What the reader will gain: This review focuses on data on fracture risk reduction and safety endpoints of PTH analogues. The adverse reactions reported most are nausea, pain in the extremities, headache and dizziness.Take home message: Exogenous PTH analogues, given as daily subcutaneous injections, stimulate bone formation, increase bone mass and bone strength, and improve calcium balance. In postmenopausal women with osteoporosis, PTH analogues reduced the risk of vertebral (PTH 1 – 34 and PTH 1 – 84) and non-vertebral fractures (only PTH 1 – 34). In men and women with glucocorticosteroid-induced osteoporosis, PTH 1 – 34 reduced the risk of vertebral fractures. In general, PTH analogues are well tolerated with an acceptable safety profile: they can be used for the prevention and treatment of fractures in postmenopausal women with severe, established osteoporosis.

Potassium bicarbonate supplementation and calcium metabolism in postmenopausal women: are we barking up the wrong tree?

A recent study of postmenopausal women has shown that the administration of 60-120 mmol potassium bicarbonate can neutralize net acid excretion and significantly lower urinary calcium (Ca). The changes in urinary calcium loss were sufficient to improve calcium balance and skeletal metabolism in these subjects. However, the design of the study was such that the relevance of these findings to the prevention and treatment of osteoporosis is suspect.

Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats

Fructus ligustri lucidi (FLL) is a widely used herb in China that is classically included in antiaging formulas for the treatment of age-related symptoms. Our laboratory previously showed that FLL could regulate calcium balance in young ovariectomized (OVX) rats. In the present study, we aimed to determine whether FLL could regulate calcium balance in aged OVX rats and to study the potential mechanisms that mediate its action in vivo. Aged OVX rats were orally administered an ethanol extract of FLL and its vehicle and fed with diets containing different levels of calcium [low calcium diet (LCD), 0.1% Ca; medium calcium diet (MCD), 0.6% Ca; and high calcium diet (HCD), 1.2% Ca] for 12 weeks. Significant reductions in urinary and fecal calcium excretion were found in the FLL-treated animals, resulting in a significant induction of calcium retention in rats fed with the MCD and HCD. FLL treatment significantly increased the serum 1,25-dihydroxyvitamin D3 level and slightly decreased the serum parathyroid hormone level in OVX rats fed with the MCD and HCD. When OVX rats were challenged by LCD, the inductions of serum parathyroid hormone and 1,25-dihydroxyvitamin D3 were decreased by FLL administration. FLL treatment significantly up-regulated duodenal vitamin D receptor and calcium transport protein 1 mRNA expression in rats fed with the HCD. FLL treatment reduced the expression of renal vitamin D receptor and 25-hydroxyvitamin D-24-hydroxylase mRNA in OVX rats fed with the LCD and MCD. Twelve weeks of FLL treatment could reduce calcium loss, modulate the parathyroid hormone-vitamin D axis, and increase vitamin D-dependent calcium transport in aged OVX rats, suggesting that FLL might be useful as an alternative medicine for improving calcium balance in postmenopausal women.

Improvement of Ca balance by Fructus Ligustri Lucidi extract in aged female rats

This study aimed to demonstrate and delineate the mechanism of action of Fructus Ligustri Lucidi (FLL) involved in improving Ca balance in aged female rats. FLL could enhance the apparent Ca absorption rate and reduce Ca excretion, via its actions on modulating the levels of calciotropic hormones and CaBPs expression. Fructus Ligustri Lucidi (FLL) is a herb classically used for the treatment of age-related symptoms in China. The present study aimed to determine if FLL could improve calcium balance in aged female rats and delineate its mechanism of action in vivo. Aged Sprague-Dawley rats (11 months of age) were orally administered with ethanol extract of FLL or its vehicle and fed with diets containing different levels of Ca (low Ca diet, LCD, 0.1% Ca; medium Ca diet, MCD, 0.6% Ca; high Ca diet, HCD, 1.2% Ca) for 12 weeks. Serum, urine and feces were collected for biochemical markers and Ca balance determination. mRNA expressions of calcium binding proteins (CaBPs) were determined by real time RT-PCR. The effects of diets and herb were analyzed by both one-way and two-way ANOVA. FLL significantly reduced fecal Ca excretion and induced apparent Ca absorption rate in rats fed with MCD and HCD. FLL increased serum 1,25(OH)(2)D(3) level and duodenal CaBP-9k mRNA expressions in all rats. Renal CaBP-28k mRNA expressions were induced in rats fed with MCD and HCD upon FLL treatment. Our study demonstrated that FLL improved Ca balance in aged female rats by increasing serum 1,25 (OH)(2)D(3) level and vitamin D-dependent CaBPs expression.

Bone calcium turnover during pregnancy and lactation in women with low calcium diets is associated with calcium intake and circulating insulin-like growth factor 1 concentrations

Few data exist on longitudinal changes in bone calcium turnover rates across pregnancy and lactation. Our aim was to characterize calcium kinetic variables and predictors of these changes across pregnancy and early lactation in women with low calcium intakes. Stable calcium isotopes were administered to 10 Brazilian women during early pregnancy (EP; weeks 10-12 of gestation), late pregnancy (LP; weeks 34-36 of gestation), and early lactation (EL; 7-8 wk postpartum). Multicompartmental modeling was used to assess the rates of bone calcium turnover in relation to calcium intakes and circulating concentrations of parathyroid hormone (PTH), insulin-like growth factor 1, and 1,25-dihydroxyvitamin D. Rates of bone calcium deposition increased significantly from EP to LP (P = 0.001) and were significantly associated with serum PTH during LP (P < or = 0.01). Rates of bone calcium resorption were also higher during LP and EL than during EP (P < or = 0.01) and were associated with both PTH (P < or = 0.01) and IGF-1 (P < or = 0.05) during LP but not during EL. Net balance in bone calcium turnover was positively associated with dietary calcium during EP (P < or = 0.01), LP (P < or = 0.01), and EL (P < or = 0.01). The mean (+/-SD) calcium intake was 463 +/- 182 mg/d and, in combination with insulin-like growth factor 1, explained 68-94% of the variability in net bone calcium balance during pregnancy and lactation. Net deficits in bone calcium balance occurred during pregnancy and lactation. Increased dietary calcium intake was associated with improved calcium balance; therefore, greater calcium intakes may minimize bone loss across pregnancy and lactation in women with habitual intakes of <500 mg calcium/d.

Long-Term Prolactin Exposure Differentially Stimulated the Transcellular and Solvent Drag-Induced Calcium Transport in the Duodenum of Ovariectomized Rats

Prolactin, having been shown to stimulate transcellular active and solvent drag-induced calcium transport in the duodenum of female rats, was postulated to improve duodenal calcium transport in estrogen-deficient rats. The aim of the present study was, therefore, to demonstrate the effects of long-term prolactin exposure produced by anterior pituitary (AP) transplantation on the duodenal calcium transport in young (9-week-old) and adult (22-week-old) ovariectomized rats. We found that ovariectomy did not alter the transcellular active duodenal calcium transport in young and adult rats fed normal calcium diet (1.0% w/w Ca) but decreased the solvent drag-induced duodenal calcium transport from 75.50 +/- 10.12 to 55.75 +/- 4.77 nmol.hr(-1).cm(-2) (P < 0.05) only in adult rats. Long-term prolactin exposure stimulated the transcellular active calcium transport in young and adult AP-grafted ovariectomized rats fed with normal calcium diet by more than 2-fold from 7.56 +/- 0.79 to 16.54 +/- 2.05 (P < 0.001) and 9.78 +/- 0.72 to 15.99 +/- 1.75 (P < 0.001) nmol.hr(-1).cm(-2), respectively. However, only the solvent drag-induced duodenal calcium transport in young rats was enhanced by prolactin from 95.51 +/- 10.64 to 163.20 +/- 18.03 nmol.hr(-1).cm(-2) (P < 0.001) whereas that in adult rats still showed a decreased flux from 75.50 +/- 10.12 to 47.77 +/- 5.42 nmol.hr(-1).cm(-2) (P < 0.05). Because oral calcium supplement has been widely used to improve calcium balance in estrogen-deficient animals, the effect of a high-calcium diet (2.0% w/w Ca) was also investigated. The results showed that stimulatory action of long-term prolactin on the transcellular active duodenal calcium transport in both young and adult rats was diminished after being fed a high-calcium diet. The same diet also abolished prolactin-enhanced solvent drag-induced duodenal calcium transport in young and further decreased that in adult AP-grafted ovariectomized rats. We concluded that the solvent drag-induced duodenal calcium transport in adult rats was decreased after ovariectomy. Long-term prolactin exposure stimulated the transcellular active duodenal calcium transport in both young and adult rats whereas enhancing the solvent drag-induced duodenal calcium transport only in young rats. Effects of prolactin were abolished by a high-calcium diet.

Effects of Potassium Alkali and Calcium Supplementation on Bone Turnover in Postmenopausal Women

Potassium citrate may improve calcium balance by conferring an alkali load. Calcium supplementation slows postmenopausal bone loss by inhibiting PTH secretion. This study explores whether combined treatment with potassium citrate and calcium citrate is more effective than either agent alone in inhibiting bone loss. In a crossover study involving 18 postmenopausal women, the following treatments were compared: potassium citrate (4.3 g or 40 mmol/d), calcium citrate (800 mg or 20 mmol/d), combined treatment, and placebo. During the last 2 d of each 2-wk phase, serum and 24-h urine were collected for assessment of calcium metabolism, alkali load, and bone turnover markers. Compared with placebo, potassium citrate provided an alkali load and significantly decreased urinary calcium without changing serum PTH (sPTH) or bone turnover markers. Calcium citrate significantly increased absorbed calcium, marginally decreased sPTH, and significantly reduced bone resorption markers. Combined treatment retained key features of potassium citrate and calcium citrate. However, more alkali was delivered than with potassium citrate alone, and absorbed calcium did not differ from calcium citrate alone. Compared with placebo, combined treatment increased urinary calcium, marginally reduced sPTH, provided a clear alkali load, and reduced the bone resorption markers serum type I collagen C-telopeptide and urinary N-telopeptide by 20.4% (P < 0.0001) and 18.2% (P = 0.005), respectively. A significant trend was noted for the decrease in bone resorption markers as treatment changed from placebo to potassium citrate to calcium citrate to combined treatment. In postmenopausal women, combined treatment with potassium citrate and calcium citrate inhibits bone resorption by providing an alkali load and increasing absorbed calcium.

A calcium homeostasis model: orchestration of fast acting PTH and calcitonin with slow calcitriol

Calcitriol is in plasma bound to transcalciferin and this results in a long calcitriol half-life in plasma (5–12 h). Abundance of bound calcitriol molecules prevents the exact and quick control of its effects and makes it an inert regulator with a time lag between the changes of calcitriol synthesis and its effect on peripheral tissues. The added regulatory inertia is here defined as: calcitriol bound/calcitriol free and it approaches value of 99. Estrogens increase transcalciferin levels. It is possible that the estrogen-induced increase in the total calcitriol plasma pool makes calcitriol effects even more inert, augmenting and prolonging the calcitriol effects and thus improving calcium balance in women. Since calcitriol synthesis in kidneys depends on the PTH level, it can be assumed that the size of the total calcitriol pool in plasma reflects more the average PTH secretion during previous hours, than the high or low peaks of PTH secretion in the same period. In other words, one or more PTH tides of short duration are followed with a late calcitriol tide that lasts for hours, and even longer lasting rise in calcitriol effects. Bone integrity depends also on the cortisol level. A possible speculation is that the main result of all profound bone effect of hypecortisolemia, might be reduction of the bone amino acids uptake, thus allowing redistribution of available proteins. Both PTH and calcitriol prevent dangerous hypocalcemia. PTH is quick in mobilizing bone calcium, while calcitriol tends to increase absorption of dietary calcium. In case of low or no dietary calcium, calcitriol mobilizes bone calcium and thus increase PTH initiated demineralization. In the case of calcium abundance, increased plasma calcium reduces PTH levels. Calcitriol plasma level (reflecting previous PTH surges) can induce both calcium absorption and bone demineralization. This two-blade action is tuned by calcitonin that reduces osteoclastic bone resorption, allowing bone deposition of abundant calcium. An overnight fast with a reduced absorption of dietary calcium, might decrease plasma calcium below the regulatory set point, inducing an increase in PTH secretion. Increased average nighttime PTH secretion induces more calcitriol to be synthesized in kidneys. The resultant late calcitriol morning and daytime tide would stimulate calcium absorption from gut, or from bone, depending on the availability of dietary calcium. Due to the described time lag in calcitriol effects, increased calcium absorption might continue during daytime, regardless of the plasma calcium level. If plasma calcium is above the set point, calcitonin will allow excess calcium to deposit in bones. A speculation based on this model is that it might be more efficient to avoid calcium rich food for dinner or supper, and to administer calcium supplementation in the morning, during the calcitriol tide.

Vitamin D Receptor (VDR) Knockout Mice Reveal VDR-Independent Regulation of Intestinal Calcium Absorption and ECaC2 and Calbindin D9k mRNA

To study the role of calbindin D(9k) (CaBP) and epithelial calcium channel ECaC2 in intestinal calcium (Ca) absorption, vitamin D receptor knockout (KO) and wild-type (WT) mice were fed either 0.5% Ca or a 2.0% Ca rescue diet starting at 21 d of age. Ca absorption and parameters involved in this process were measured at 60 or 90 d of age. Compared with WT, KO mice fed the 0.5% Ca diet had higher plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], and lower plasma Ca and insulin-like growth factor-I (IGF-I). Duodenal Ca absorption (% Ca absorbed) in KO mice was reduced 71% relative to WT mice and was associated with 55% lower CaBP mRNA, 47% lower CaBP protein and 95% lower ECaC2 mRNA levels. Compared with WT mice, the percentage of Ca absorbed in KO mice fed the 0.5% Ca diet was inappropriately low for the level of duodenal CaBP. The 2% Ca rescue diet normalized plasma Ca, prevented osteomalacia, increased growth and plasma IGF-I levels, but did not normalize plasma PTH or 1,25(OH)(2)D(3) in KO mice. In addition, the relationship between CaBP protein and the percentage of Ca absorbed was normalized, whereas ECaC2 mRNA fell to near zero. Our data demonstrate that higher CaBP levels do not ensure high rates of duodenal Ca absorption and that transcellular Ca absorption can occur even when ECaC2 gene expression is very low. In addition, our data suggest that the 2% Ca diet promotes a vitamin D receptor-independent anabolic effect on bone formation and calcium absorption, leading to improved calcium balance even in the presence of high PTH levels.

Prevention of Spinal Bone Loss by Potassium Citrate in Cases of Calcium Urolithiasis

We determine if potassium citrate treatment stabilizes spinal bone density among patients with recurrent calcium oxalate nephrolithiasis. We studied a group of 16 men and 5 women with stones taking potassium citrate from 11 to 120 months. They represented all patients from the Stone Clinic who took potassium citrate alone for at least 11 months. L2-L4 bone mineral density data before and after potassium citrate treatment were retrieved retrospectively and analyzed. In the combined group L2-L4 bone mineral density increased significantly by 3.1% over mean duration of 44 months. Z score, corrected for age matched normal values, increased significantly by 3.8%. Urinary pH, citrate and potassium increased significantly during treatment but urinary calcium did not change. Potassium citrate, a commonly used drug for the prevention of recurrent nephrolithiasis, may avert age dependent bone loss. Spinal bone density increased in most patients when it normally decreases.

Effects of bioactive substances in milk on mineral and trace element metabolism with special reference to casein phosphopeptides.

Bioactivity of phosphopeptides yielded after tryptic hydrolysis of casein (CPP) was reported more than 50 years ago when CPP were found to improve calcium balance in rachitic newborns. Several investigations have been carried out to study the effects of CPP mainly on calcium metabolism but also on other minerals like iron and zinc. Most of the experiments were in vitro studies or short-term experiments like the effects of CPP after single meals or their effect on mineral disappearance from intestinal everted sac or ligated loop. Investigations on calcium balance were also mainly short term, i.e. 3-4 weeks, and mainly done in rats. A few experiments have been carried out in minipigs, an animal model that is closer to the human than the rat. Studies in human were rare and short term. To date a variety of other peptides have been isolated after enzymatic hydrolysis, and some have been investigated for bioactivity, with equivocal findings. Bioactivity of phosphopeptides seemed to be more obvious when investigations were done in vitro or short term. Results were less clear in metabolic balance studies, especially under physiological conditions. The composition of the basal diet, i.e. content of calcium and phytate, or the protein source had a significant impact on the effect of phosphopeptides. It was concluded that phosphopeptides revealed positive effects on mineral solubility and absorbability, and bone mineralisation under certain experimental conditions. Accordingly they could have a beneficial effect on bone health for some groups of the population.

Reduced dietary phosphate improves calcium balance in the ovariectomized rat

Reduced dietary phosphate improves calcium balance in the ovariectomized rat