Intestinal mitochondrial calcium uptake during adaptation to dietary calcium restriction

In order to evaluate the role of mitochondrial calcium uptake in intestinal calcium absorption, the effect of adaptation to dietary calcium deficiency on the in vitro uptake of calcium by isolated duodenal mitochondria was studied. Experiments were performed utilizing 28-day-old cockerels which had received a diet adequate in vitamin D₃ and phosphate and containing either 0.08% or 1.20% calcium. Mitochondrial⁴⁵Ca uptake from chicks deprived of dietary calcium was not significantly different from controls. These results suggest that increased calcium uptake by intestinal mitochondria is not crucial for adaptation to a low calcium diet.     

Influence of age on effects of endogenous 1,25-dihydroxyvitamin D on calcium absorption in normal women

Recent reports of increases in serum 1,25-dihydroxyvitamin D [1,25(OH₂)D] concentration with aging despite no changes or decreases in calcium absorption suggest that elderly women have intestinal resistance to vitamin D action. Thus, in 15 young adult (30±1 year) and 15 elderly (74±1 year) women (mean±SE), we assessed the responsiveness of intestinal calcium absorption to increases in circulating 1,25(OH)₂D induced by 4 days of an experimental diet (150 mg calcium and 1600 mg phosphorus daily). True fractional calcium absorption (FCA) (⁴⁴Ca mixed with food and ⁴²Ca given intravenously, then their ratio in urine measured by mass spectrometry) was determined. Baseline serum intact parathyroid hormone (PTH) concentration was higher in the older women (P=0.01) whereas serum 1,25(OH)₂D concentration and true FCA were similar. In both groups, serum 1,25(OH)₂D concentrations increased (P<0.002) on the experimental diet. After 4 days on the diet, serum 1,25(OH)₂D increased over baseline by 30.5 and 35.6% and, despite these increases, true FCA was 40±3 versus 40±4%/24 hours (NS between groups) in the young and elderly women, respectively. These data suggest that either elderly women have normal intestinal responsiveness to vitamin D or that the resistance to it is too mild to be detected by these methods.     

Intestinal calcium absorption from different calcium preparations: Influence of anion and solubility

Not only is the calcium content of a preparation significant for providing adequate calcium supplementation for the prophylaxis and therapy of osteoporosis, but also its bioavailablity is of essential importance. In the present study, the bioavailability of calcium citrate and calcium lactogluconate/carbonate from a therapeutic dose (= 500 mg Ca²⁺) was compared in men aged between 45 and 60 years on an intra-individual basis. Calcium citrate was administered both as a solution and as a suspension to 18 healthy volunteers. Using a double-isotope method, the intestinal absorption from the three preparations was determined in randomized order at intervals of 2–4 weeks. The stable isotope⁴⁴Ca (20 mg), in highly enriched form, was added in each case to the ready-to-drink solutions and, at the same time, a sterile and pyrogen-free solution containing 5 mg of the stable isotope⁴²Ca was injected intravenously. The intestinal calcium absorption was then determined after 24 h on the basis of the ratio of the two isotopes in the plasma. There was a significantly higher absorption of 29% from the citrate solution than from the lactogluconate/carbonate solution (25%). Absorption from the citrate suspension was similar to that from the lactogluconate/carbonate solution. While no correlation was found between the measured values for calcium absorption from the three preparations and the plasma concentration of 1,25-dihydroxycholecalciferol, significant inverse correlations with the basal parathyroid hormone concentration were observed for the citrate and lactogluconate/carbonate solution. The results of this study show that quantitative data on intestinal calcium absorption can be obtained without employing radioactive isotopes in humans. Moreover, they show that calcium absorption is not determined only by the solubility and the degree of ionization of the calcium salt administered, but rather that it is of a complex nature.     

Adult-type hypolactasia and calcium availability: decreased calcium intake or impaired calcium absorption?

Summary Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. Introduction and hypothesis Adult-type hypolactasia (HL) defined by the LCT_(−13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). Methods Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H₂ breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. Results LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 ± 629 μg/L vs. 2020 ± 1130 μg/L in lactose tolerant subjects, p = 0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. Conclusion Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects.     

Intestinal calcium absorption,serum phosphate,and parathyroid hormone in patients with chronic renal failure and osteodystrophy before and during hemodialysis

Summary In 34 patients with chronic renal failure (CRF), fractional⁴⁷calcium absorption (Fa⁴⁷Ca) was measured by an external counting method. A significant correlation was found with impairment of renal function, as expressed by the creatinine clearance. There was also a significant correlation of Fa⁴⁷Ca with the serum phosphate (SeP) level and of immunoreactive parathyroid hormone (iPTH) with renal function. When the relationship of both SeP and Fa⁴⁷Ca with creatinine clearance was excluded, no partial correlation between SeP and Fa⁴⁷Ca appeared to exist. A significant increase of Fa⁴⁷Ca and serum Ca and a significant decrease of SeP and iPTH were found in 12 patients 2 to 15 months after they were put on intermittent hemodialysis. The possible influence of SeP on intestinal calcium absorption is discussed, and it is suggested that impairment of intestinal absorption of calcium is not a main factor in development of renal osteodystrophy.     

Interrelation of cortisone and 1,25 dihydroxycholecalciferol on intestinal calcium and phosphate absorption

Summary The interrelation of glucocorticoids and 1,25 dihydroxycholecalciferol (1,25(OH)₂D₃) on intestinal calcium and phosphate absorption was investigated. The active and passive transport of calcium and phosphate was evaluated by thein situ intestinal loop technique. Administration of cortisone resulted in a decrease of the luminal fluid and an increase of the luminal calcium and phosphate concentration. Under active transport conditions, administration of cortisone resulted in a decrease of net calcium absorption through two mechanisms: (1) depressed vitamin D-dependent calcium absorption, (2) increased vitamin D-independent calcium backflux. The enhancement of bidirectional phosphate flux by cortisone was independent of 1,25(OH)₂D₃. An enhancement of water movement by cortisone resulted in an increase of luminal calcium and phosphate concentration which favors the passive diffusion of these ions. Enhanced calcium diffusion by cortisone compensates for the inhibitory effect of cortisone on vitamin D-dependent calcium transport. However, enhanced phosphate diffusion by cortisone is additive to the effect of 1,25(OH)₂D₃.     

Intestinal mitochondrial calcium uptake during adaptation to dietary calcium restriction

In order to evaluate the role of mitochondrial calcium uptake in intestinal calcium absorption, the effect of adaptation to dietary calcium deficiency on the in vitro uptake of calcium by isolated duodenal mitochondria was studied. Experiments were performed utilizing 28-day-old cockerels which had received a diet adequate in vitamin D₃ and phosphate and containing either 0.08% or 1.20% calcium. Mitochondrial⁴⁵Ca uptake from chicks deprived of dietary calcium was not significantly different from controls. These results suggest that increased calcium uptake by intestinal mitochondria is not crucial for adaptation to a low calcium diet.     

The clinical use of orally administered47Ca for the investigation of intestinal calcium absorption

Intestinal calcium absorption was measured by the oral administration of calcium⁴⁷ (in milk as a carrier) to 15 normals and 30 patients and by following the blood concentration at two hours, the twenty four hour urine excretion and cumulative faecal excretion of the isotope. Simultaneous calcium balances allowed an estimate of calcium absorption to be made and this correlated with the blood and faecal data once an allowance was made for the endogenous secretion. This was found to be highly variable, mean values in the patients being 300 mg/24 hours. A slow type of intestinal absorption was found in the osteoporotic group of patients.Members of the External Scientific Staff of the Medical Research Council.     

Reduced absorption of45calcium from isolated duodenal segmentsin vitro in juvenile but not adult X-linked hypophosphatemic mice

Summary In juvenile X-linked hypophosphatemic (Hyp) mice, whole body calcium balances are significantly lower than in genetically normal mice. This is associated with low duodenal vitamin D-dependent calcium-binding protein and a failure of skeletal mineralization. To seek more specific evidence of an intestinal defect in these mice, absorption of⁴⁵Ca was measured in isolated duodenal segmentsin vivo in mice from 2–13 weeks of age. The duodenum was isolated by sutures and⁴⁵Ca was injected into the lumen in 150 mM NaCl and 2 mM CaCl₂ at pH=7.2. Absorption was measured by the amount of isotope remaining in the lumen and by the plasma isotope level. HemizygousHyp male and heterozygousHyp female mice absorbed significantly less⁴⁵Ca at 4 and 7 weeks of age than genetically normal mice whileHyp mice at 2, 10, and 13 weeks of age were not significantly affected. At 4 and 7 weeks of age, theHyp mice also had significantly reduced plasma radioactivity midway through the collection period as well as at the end of the period. To explore a possible mechanism for this malabsorption, 1,25(OH)₂-vitamin D receptors were measured in cytosol prepared from 4-week-old normal andHyp duodenum. There were non-significant differences between the normal andHyp mice in both binding affinity, K_d, and the number of receptors, n_max. In conclusion, juvenileHyp mice at 4 and 7 weeks of ages malabsorbed calcium from their duodenum.Hyp mice younger than this period were not affected nor were adultHyp mice. This delay in the development of calcium absorption was not caused by a delay in the appearance of intestinal receptors for 1,25(OH)₂D.     

Calcium absorption measurements in normal subjects in determining calcium deposition during prolonged hypokinesia and with and without calcium loading

Measuring calcium (Ca) absorption, Ca balance and Ca level in serum,feces and urine during HK (hypokinesia) with and without Ca loading, the aim of this study was to disclose if prolonged HK could reduce Ca deposition more with or without Ca load contributing to greater Ca imbalance. Studies were conducted during 30-days pre-HK and 364-days HK. Forty male normal volunteers 23.7 ± 6.0 years of age were chosen as subjects. They were divided into four groups: unloaded active control subjects (UACS), unloaded hypokinetic subjects (UHKS), loaded active control subjects (LACS), loaded hypokinetic subjects (LHKS). All hypokinetic subjects were walking average distances of 0.5 ± 0.2 km day^–1, and active control subjects were running average distances of 6.6 ± 1.2 km day^–1. LACS and LHKS were loaded with 1.3 mmol calcium lactate/kg body wt. Before Ca load, fecal Ca loss, urinary Ca and phosphate (P) losses, Ca imbalance, serum ionized calcium (Ca_I), P and total Ca (Ca_t) levels increased significantly. (P < 0.05) with time, and serum intact parathyroid hormone (iPTH), 1.25 dihydroxyvitamin D (1.25(OH)₂D₃) levels and Ca absorption, decreased significantly (P < 0.05) with time in LHKS and UHKS compared with their pre-HK values and their respective active controls (LACS and UACS). After Ca load, however, Ca absorption, serum iPTH and 1.25 (OH)₂D₃ levels decreased significantly (P < 0.05) more with time, while fecal Ca loss, urinary Ca and P excretion and Ca imbalance increased significantly (P < 0.05) more with time in LHKS than UHKS. Conversely, before and after Ca load, fecal Ca excretion, urinary P and Ca loss, serum Ca_I, P, Ca, iPTH and 1.25 (OH)₂D₃ levels, Ca absorption and Ca balance did not change in LACS and UACS compared with their pre-HK values. The greater Ca losses with than without Ca load have shown that the more Ca is consumed the more Ca is eliminated during HK and Ca imbalance. The significant increase of Ca loss with Ca imbalance demonstrated reduced Ca deposition. Dissociation between Ca loss and Ca imbalance demonstrated reduced Ca deposition as the mechanism of Ca imbalance development during HK.     

Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis

Energy-dependent intestinal calcium absorption is important for the maintenance of calcium and bone homeostasis, especially when dietary calcium supply is restricted. The active form of vitamin D, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], is a crucial regulator of this process and increases the expression of the transient receptor potential vanilloid 6 (Trpv6) calcium channel that mediates calcium transfer across the intestinal apical membrane. Genetic inactivation of Trpv6 in mice (Trpv6^?/?) showed, however, that TRPV6 is redundant for intestinal calcium absorption when dietary calcium content is normal/high and passive diffusion likely contributes to maintain normal serum calcium levels. On the other hand, Trpv6 inactivation impaired the increase in intestinal calcium transport following calcium restriction, however without resulting in hypocalcemia. A possible explanation is that normocalcemia is maintained at the expense of bone homeostasis, a hypothesis investigated in this study.In this study, we thoroughly analyzed the bone phenotype of Trpv6^?/? mice receiving a normal (～ 1%) or low (～ 0.02%) calcium diet from weaning onwards using micro-computed tomography, histomorphometry and serum parameters.When dietary supply of calcium is normal, Trpv6 inactivation did not affect growth plate morphology, bone mass and remodeling parameters in young adult or aging mice. Restricting dietary calcium had no effect on serum calcium levels and resulted in a comparable reduction in bone mass accrual in Trpv6^+/+ and Trpv6^?/? mice (? 35% and 45% respectively). This decrease in bone mass was associated with a similar increase in bone resorption, whereas serum osteocalcin levels and the amount of unmineralized bone matrix were only significantly increased in Trpv6^?/? mice.Taken together, our findings indicate that TRPV6 contributes to intestinal calcium transport when dietary calcium supply is limited and in this condition indirectly regulates bone formation and/or mineralization.     

Potentiation of the effects ofSolanum malacoxylon extracts on rat intestinal phosphate and calcium absorption by incubation with ruminal fluid

Summary The effects of a partially purified aqueous extract ofSolanum malacoxylon (SM) leaves and of an SM extract incubated with ruminal fluid (RF) prior to administration on intestinal phosphate and calcium absorption in rachitic rats were compared with 1, 25-dihydroxy-vitamin D₃[1,25-(OH)₂-D₃] using a duodenal loop in situ method. The time course responses elicited by both extracts were qualitatively similar to that of 1, 25-(OH)₂-D₃. However, a single dose of SMRF was significantly more effective in stimulating³²P absorption than an equivalent dose of SM. Part of this difference can be accounted for by incomplete saturation of the phosphate transport system with the level of SM employed. Treatment with rumen potentiated the effects of SM on⁴⁵Ca absorption to a lesser extent. Extraction of SMRF with nonpolar organic solvents and purification of the lipid extract by chromatography on Silica Gel G thin-layer plates and on Sephadex LH-20 columns yield two fractions which promote intestinal³²P absorption. The bioactive fraction eluting first from the Sephadex LH-20 column migrates similarly as 1,25-(OH)₂-D₃. The greater effectiveness of SMRF extracts on intestinal phosphate and calcium absorption may be tentatively attributed to the release of 1,25-(OH)₂-D₃ from the corresponding glycoside, shown previously to be present in SM, and to steroid modification during incubation with rumen.     

The assessment of intestinal calcium absorption using stable strontium

Summary The availability of currently used methods of measuring. intestinal calcium absorption is limited by their expense and complexity. Since this measurement may be important in selecting appropriate therapies for patients with osteoporosis, a simpler procedure is required. This paper describes a test which measures the intestinal absorption of stable strontium. A comparison of this test with the single-isotope radio-calcium absorption test in the same group of patients showed a close correlation between the fractional absorption rates of the two elements (r=0.93,P<0.001). Subjects were correctly categorized as having normal or low absorption in 12 out of 13 cases (92%) and the value in the misclassified subject was at the borderline between normal and low calcium absorption. The convenience, low cost, and freedom from radioactivity of stable strontium make it suitable for routine clinical use and, if necessary, repeated testing. If these early results are confirmed, this test will make the assessment of calcium absorption much more widely available.     

The effects of stable strontium on calcium metabolism.: II. Effects of 1α-hydroxyvitamin D3 in strontium-fed rats,and inhibitory effect of strontium on bone resorptionin vitro

It has been postulated that the effect of strontium on bone metabolism due to the reduced plasma 1,25-dihydroxyvitamin D₃ level following the inhibition of 1α-hydroxylation by strontium. The effects of strontium were examined on intestinal calcium absorption when rats were received synthetic 1α-hydroxyvitamin D₃. Four groups of rats at the age of 36 days were fed a semi-synthetic vitamin D-deficient diet for 4 weeks containing 1% strontium and vitamin D₃ (Sr-D group), 1% strontium and 1α-hydroxyvitamin D₃ (Sr-α group), vitamin D₃ (Co-D group), or 1α-hydroxyvitamin D₃ (Co- α group), respectively. At the age of 60 days, calcium and strontium balance studies were conducted to determine intestinal calcium absorption over a 3-day period, and 1,25-dihydroxyvitamin D level was then measured. Serum 1,25-dihydroxyvitamin D in Sr-D group was undetectable, and intestinal calcium absorption significantly decreased. Replacement of vitamin D₃ with 1α-hydroxyvitamin D₃ recovered serum 1,25-dihydroxyvitamin D to the level in Co-D group. However, this substitution in Sr-α group failed to increase intestinal calcium absorption. We also examined the direct of strontium on bone resorption using⁴⁵Ca pre-labeled mouse calvaria. Strontium was injected every day until sacrifice, and percent⁴⁵Ca release from cultured calvariae was measured. Bone resorption was inhibited by strontium dose-dependently in groups which had and had not received parathyroid hormone in culture. These results suggest that strontium inhibits intestinal calcium absorption and has a direct inhibitory effect on bone resorption.     

Malabsorption of calcium in corticosteroid-induced osteoporosis

Summary We have examined the relation between radiocalcium absorption and serum 1,25-dihydroxy-vitamin D [1,25(OH)₂D₃] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age-matched with the “normal” corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)₂D₃ in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid-treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)₂D₃ levels. This apparent resistance to the intestinal action of 1,25(OH)₂D₃ was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)₂D₃ level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions.     

Absorbability of the calcium in a high-calcium mineral water

The availability of the calcium contained in a high-calcium mineral water (Sangemini), popular in Italy, was compared in 18 healthy women with the availability of milk calcium ingested at the same calcium load, using⁴⁵Ca as the tracer in a randomized cross-over design. At an ingested calcium load of 2.5 mmol, absorption fraction averaged 0.433 for milk and 0.475 for Sangemini water. The mean quotient of the two (Sangemini/milk) was 1.129 (±0.056, SEM,P<0.05). The calcium of Sangemini water is thus highly bioavailable, and at least as bioavailable as milk calcium.     

Intestinal calcium absorption during hyperinsulinemic euglycemic glucose clamp in healthy humans

Summary The influence of postprandial-like plasma insulin levels on intestinal calcium absorption (CaA) was studied in 9 health men. On separate occasions, they received either an i.v. infusion of 40 mU/m² minute synthetic human insulin as well as a variable glucose infusion in order to clamp the plasma glucose at the baseline level (=glucose clamp), or insulin- and glucose-free vehicle infusions (=vehicle). During these infusions, an oral load containing 326 mg Ca in the form of Ca chloride was administered and CaA was determined thereafter with a⁴⁷Ca/⁸⁵Sr double tracer method. During glucose clamp, mean plasma insulin was 172 ±(1 SEM) 10 as compared to 6±1 μU/ml during vehicle infusions. During the clamp, 3-hour cumulative CaA rose significantly by 14% as compared to vehicle (39.2±2.5 vs. 34.4±2%,P<0.02). At the same time, serum potassium and phosphorus dropped significantly, whereas serum parathyroid hormone (PTH) and 1,25(OH)₂D levels were unchanged as compared to vehicle. The urinary excretions of potassium, sodium, and inorganic phosphorus as well as the urinary specific activity of⁴⁷Ca, dropped significantly during glucose clamp, whereas the urinary excretion of cAMP was unchanged as compared to vehicle. The results suggest that, under the conditions of euglycemic hyper-insulinemic clamp, insulin stimulates CaA of healthy humans in a PTH- and 1,25(OH)₂D-independent manner. Insulin may thus possibly be regarded as a factor participating in the regulation of CaA in humans.     

Extra-intestinal calcium handling contributes to normal serum calcium levels when intestinal calcium absorption is suboptimal

The active form of vitamin D, 1,25(OH)₂D, is a crucial regulator of calcium homeostasis, especially through stimulation of intestinal calcium transport. Lack of intestinal vitamin D receptor (VDR) signaling does however not result in hypocalcemia, because the increased 1,25(OH)₂D levels stimulate calcium handling in extra-intestinal tissues. Systemic VDR deficiency, on the other hand, results in hypocalcemia because calcium handling is impaired not only in the intestine, but also in kidney and bone. It remains however unclear whether low intestinal VDR activity, as observed during aging, is sufficient for intestinal calcium transport and for mineral and bone homeostasis. To this end, we generated mice that expressed the Vdr exclusively in the gut, but at reduced levels. We found that ~ 15% of intestinal VDR expression greatly prevented the Vdr null phenotype in young-adult mice, including the severe hypocalcemia. Serum calcium levels were, however, in the low-normal range, which may be due to the suboptimal intestinal calcium absorption, renal calcium loss, insufficient increase in bone resorption and normal calcium incorporation in the bone matrix. In conclusion, our results indicate that low intestinal VDR levels improve intestinal calcium absorption compared to Vdr null mice, but also show that 1,25(OH)₂D-mediated fine-tuning of renal calcium reabsorption and bone mineralization and resorption is required to maintain fully normal serum calcium levels.     

Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway

Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)₂D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)₂D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1α-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)₂D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)₂D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.     

Classification of idiopathic hypercalciuric patients by isotopic calcium absorption: A comparison with oral calcium tolerance test

Summary To test the accuracy of calcium tolerance test in estimating calcium absorption, we have measured the radioactive calcium absorption (expressed as Fx) in 27 patients with IH and renal calcium stones. The results of this test were compared with those of a standard oral calcium tolerance test. Although only seven of nine AH patients displayed normal fasting calcium excretion, they all displayed Fx values above normal and a normal parathyroid activity. Conversely, only 5 of our 18 RH patients demonstrated a hyperabsorption of radioactive calcium and an elevation in iPTH and cAMP above normal limits, yet all of them showed an increased calciuric response to an oral calcium challenge. Calcium absorption was inversely related to iPTH (r=−082;P<0.001) and cAMP (r=−064P<0.05) in AH, but directly proportional to these parameters (r=0.62P<0.001 andr=0.46P<0.05, respectively) in RH patients. In view of these results, two ratios, iPTH/Fx and cAMP/Fx were used to discriminate between the two groups of patients. Both ratios were over normal limits in all RH patients and within normal range in all but one AH patient. Furthermore, no overlap was found between the two groups. Conversely, we were unable to completely separate AH from RH subjects on the basis of the oral calcium tolerance test, since in both groups the fasting and the absolute (or percentage) changes in urinary calcium, cAMP and blood iPTH levels following oral calcium loading, overlapped in each instance. The result of this study indicates that two indices, iPTH/Fx and cAMP/Fx, may prove particularly useful in differentiating AH from RH patients. Furthermore, since only a subgroup of patients with an abnormal calciuric response to an oral calcium load manifest an increase in calcium absorption, it is concluded that the calcium tolerance test overestimates calcium absorption in IH. Supported in part by Grant No. 5T32 AM0703310