Poor Calcium Absorption Research Articles

Vitamin D and bone health status in beta thalassemia patients-systematic review.

Thalassemia is a chronic congenital disease characterized by a combination of endocrine and metabolic disorders. Bone disease is a very common complication related to the poor absorption of calcium, the secondary chronic renal disease with low vitamin D, as well as multiple endocrine risk factors. The aim of this systematic review was to estimate the prevalence of vitamin D deficiency in thalassemia, as well as its association with osteoporosis/low bone mass. A systematic review was carried out using PubMed/Medline, Cochrane, and EBSCO databases. The methodological quality of the included studies was assessed with the validated Newcastle-Ottawa Quality Assessment Scale adapted for cross-sectional studies and cohort studies respectfully and the Cochrane Collaboration for clinical trials. After application of predetermined exclusion criteria compatible with the PICOS process, a total of 12 suitable articles were identified. The prevalence of vitamin D deficiency varied considerably. Only five of the reviewed studies examined the correlation between vitamin D levels and BMD of which just three showed a statistically significant positive association of mild/moderate grade. Vitamin D deficiency is a common comorbidity in patients with thalassemia. However, both its prevalence and its severity vary considerably in different populations, and existing evidence is insufficient to conclude whether vitamin D supplementation is also associated with BMD improvement in this special population group.

Calcium content, in vitro digestibility, and bioaccessibility in leaves of spinach (Spinacia oleracea), sweet potato (Ipomea batatas), and drumstick tree (Moringa oleifera)

Low calcium intake, poor calcium absorption, excessive calcium losses, or some combination of these factors contribute to calcium deficiency diseases. Calcium insufficiency is associated with osteoporosis, hypertension and colon cancer among other diseases. For individuals who do not have access to milk and dairy products, do not tolerate them, or prefer not to consume them, plants may be  alternative sources of calcium. However, calcium bioavailability may be low in plant foods because calcium forms complexes with oxalates, phytate and other competing minerals.  The objective of this study was to compare the calcium content, digestibility and bioaccessibility in the leaves of spinach ( Spinacia oleracea) , sweet potato ( Ipomea batatas ), and drumstick tree ( Moringa oleifera ). Calcium content was analyzed in dry leaf powder by atomic absorption, followed by a two-stage in vitro digestion and dialysis against a mock serum solution to determine calcium digestibility and bioaccessibility. Moringa oleifera had higher calcium content than spinach and sweet potato leaves: 1.54±0.11% of dry matter for three Moringa samples (two African and one from India), and 0.99±0.001 and 1.06±0.001, respectively, in spinach and sweet potato leaves. The mean in vitro calcium digestibility was 1.62±0.08% in spinach, 3.4±0.68% in sweet potato leaves and 33.7±9.6% for Moringa . A dialysis system was designed to model bioaccessibility of calcium, revealing that bioaccessible calcium in sweet potato leaves was a non-significant 1.4 times higher and in Moringa was 9.2 to 19.4 times higher than in spinach. Therefore, the calcium contained in Moringa leaves does not appear to be associated with poorly bioavailable complexes such as oxalate. We confirmed previous reports that bioaccessibility of the calcium is low in spinach. These findings imply that increased utilization of Ipomea batatas and Moringa oleifera leaves might increase calcium intake in people in tropical and warm temperate regions where these plants grow, or these plants might become a valuable export crop.

Calcium content, in vitro digestibility, and bioaccessibility in leaves of spinach (Spinacia oleracea), sweet potato (Ipomea batatas), and drumstick tree (Moringa oleifera)

Low calcium intake, poor calcium absorption, excessive calcium losses, or some combination of these factors contribute to calcium deficiency diseases. Calcium insufficiency is associated with osteoporosis, hypertension and colon cancer among other diseases. For individuals who do not have access to milk and dairy products, do not tolerate them, or prefer not to consume them, plants may be alternative sources of calcium. However, calcium bioavailability may be low in plant foods because calcium forms complexes with oxalates, phytate and other competing minerals. The objective of this study was to compare the calcium content, digestibility and bioaccessibility in the leaves of spinach (Spinacia oleracea), sweet potato (Ipomea batatas), and drumstick tree (Moringa oleifera). Calcium content was analyzed in dry leaf powder by atomic absorption, followed by a two-stage in vitro digestion and dialysis against a mock serum solution to determine calcium digestibility and bioaccessibility. Moringa oleifera had higher calcium content than spinach and sweet potato leaves: 1.54±0.11% of dry matter for three Moringa samples (two African and one from India), and 0.99±0.001 and 1.06±0.001, respectively, in spinach and sweet potato leaves. The mean in vitro calcium digestibility was 1.62±0.08% in spinach, 3.4±0.68% in sweet potato leaves and 33.7±9.6% for Moringa. A dialysis system was designed to model bioaccessibility of calcium, revealing that bioaccessible calcium in sweet potato leaves was a non-significant 1.4 times higher and in Moringa was 9.2 to 19.4 times higher than in spinach. Therefore, the calcium contained in Moringa leaves does not appear to be associated with poorly bioavailable complexes such as oxalate. We confirmed previous reports that bioaccessibility of the calcium is low in spinach. These findings imply that increased utilization of Ipomea batatas and Moringa oleifera leaves might increase calcium intake in people in tropical and warm temperate regions where these plants grow, or these plants might become a valuable export crop.

Optimal Vitamin D Status

In the July issue of the Journal, Hansen et al.1 presented results of calcium absorption measurements in postmenopausal women studied at low (22 ng/ml) and high (64 ng/ml) vitamin D status. They report a statistically significant improvement in absorption efficiency (from 24% to 27%) but concluded that this improvement is too small to make much of a difference and that, therefore, the vitamin D status of individuals with 25(OH)D levels <30 ng/ml should not be designated “insufficient.” Although quantitatively less than the result we had previously reported,2 the results of Hansen et al. are qualitatively confirmatory of our own findings, as are the results of Kendler et al.3 Now three studies-the only work of the sort in the world literature-point to the same conclusion: Raising serum 25(OH)D from basal values in the range of 20–25 ng/ml improves calcium absorption efficiency. What remains at issue is how much of a difference that improvement makes. The response found by Hansen et al., the smallest of the three reported effects, amounts to a 12.5% improvement in absorption efficiency. [Actually, it is slightly more than that (effectively equivalent to 13.9%) when one takes into consideration the countervailing secretion of calcium into the gut.4] Taking that figure and applying it to an intake of 1000 mg Ca/d (the recommended intake for premenopausal women) results in 34 mg additional absorbed Ca/d. This translates to 12.4 g Ca/yr, or a potential gain/loss of >30% of the skeleton in a 25-yr period. At the 1200-mg Ca intake level recommended for postmenopausal women, the difference would be +41 mg/d. I thus conclude that even the low estimate of Hansen et al. is clinically significant. Moreover, pooling the values from all three studies, truncating the rise in 25(OH)D at 32 ng/ml, and weighting for sample size yields a mean increase in absorption fraction of 0.0132/ng/ml, or a rise in absorption fraction of 0.13 for a change in 25(OH)D from 20 to 30 ng/ml. This is a biologically large and important effect. Perhaps what is most remarkable is the fact that the three studies showed any effect at all of improved 25(OH)D status. Although in pharmacologic doses, 25(OH)D has been shown to increase calcium absorption in its own right,5 under physiological circumstances, the body regulates calcium absorption efficiency by controlling the secretion of 1,25(OH)2D. It is a commonplace observation to those who measure calcium absorption that individuals with full vitamin D repletion (by any criterion) will often have low absorption efficiencies, reflecting the fact that the body has no perceived need for extra calcium. Thus, it is probably an oversimplification (which we and others have been guilty of in the past) to postulate that vitamin D causes calcium absorption. It seems better to conceptualize the action of vitamin D in this regard as enabling physiological regulation of calcium absorption rather than directly causing it. Thus, in studies such as the three that have been performed to date, the rise in absorption efficiency in women given vitamin D would seem to reflect the fact that they were not able to regulate absorption optimally at their prevailing levels of 25(OH)D. How 25(OH)D functions in this regard is unclear, but there is a possible parallel in the role of serum 25(OH)D in enabling macrophage response to Mycobacterium tuberculosis.6 There the intracellular synthesis of 1,25(OH)2D in the macrophage is dependent on the ambient concentration of 25(OH)D. The 1-α-hydroxylation is not caused by the 25(OH)D but by the cellular genomic response to the tuberculosis antigen. However, this response needs an adequate quantity of 25(OH)D to be fully expressed. This is, I believe, a useful illustration of the distinction between an enabling and a causative effect of 25(OH)D. An instance of the fact that the body needs both molecules to stimulate and sustain calcium absorption is seen in the fact that patients with nutritional vitamin D deficiency and osteomalacia, who invariably have poor calcium absorption, commonly have normal to high levels of 1,25(OH)2D but low levels of 25(OH)D. Clearly, much more work needs to be done to understand the constructive interaction between the two molecules.

Osteoporosis in celiac disease and in endocrine and reproductive disorders

As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density (BMD), the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note: indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1beta, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primary and secondary endocrine pathologies are important for the prevention of damage to the bones.

Does the response of bone mass to calcium supplements depend on calcium absorption efficiency?

Calcium supplements can reduce bone resorption and slow bone loss after the menopause, but these effects may be limited by poor intestinal absorption. Since the increase in blood ionised calcium and decrease in serum parathyroid hormone after a calcium load are diminished in patients with poor calcium absorption, we aimed to see whether the response of bone mineral content (BMC) to calcium is related to initial calcium absorption. We retrospectively examined the changes in forearm BMC in 164 patients (139 women and 25 men) receiving calcium therapy alone for low bone density in a university hospital. BMC was measured in a Molsgaard single energy absorptiometer and calcium absorption in a single blood sample 1 h after a dose of 5 microCi (45)Ca in 20 mg calcium carrier. Results were analysed by simple and multiple regression analysis. Mean forearm BMC did not change significantly over the mean 43 (S.D., 33) months of treatment (1.023 (0.247) to 1.017 (0.246) g/cm). The annual percentage of change was positively related to both body weight (r=0.180; P=0.020) and radiocalcium absorption (r=0.185; P=0.017). Multiple linear regression confirmed that both variables contributed to the change in BMC (P=0.023 and 0.019 respectively). The mean annual percentage of change in BMC on calcium therapy was not related to age, initial BMC, serum 1,25-dihydroxyvitamin D or fasting urinary calcium/creatinine ratio. These results support our earlier studies which suggest that poor calcium absorption limits the response of bone to calcium supplements.

Bone Density in Axial and Appendicular Skeleton in Patients with Lactose Intolerance: Influence of Calcium Intake and Vitamin D Status

Background: Lactose intolerance (LI) is a common enzymatic insufficiency, manifesting by poor tolerance of dairy products, leading to low calcium intake and poor calcium absorption from dairy products. These changes might lead to an impairment of bone metabolism [1].Objectives: To evaluate the impact of LI on quantitative bone parameters in axial and appendicular skeletal sites. To assess the impact of calcium intake from dairy and non-dairy nutritional sources, calcium regulating hormones and bone turnover on quantitative bone parameters in LI patients.Methods: We evaluated calcium intake and bone status in sixty-six patients with LI, 49 women and 17 men, aged 20 to 78. Bone mass was assessed at the lumbar spine (LS), total hip (TH) and femoral neck (FN) by dual-energy x-ray absorptiometry (DEXA) and at the radius, tibia, phalanx by quantitative ultrasound. Serum calcium, albumin, inorganic phosphate, calcium regulating hormones and markers of bone turnover were evaluated.Results: Total daily calcium intake was below the recommended by the American Dietetic Association [2] in all study participants (mean 692 mg/day ± 162). Elevated level of urinary deoxypyridinoline crosslinks (DPD) was observed in 63 (96%) patients and was negatively correlated with total daily calcium intake (r = −0.998, p = 0.025) and with nondairy calcium intake (r = −0.34, p = 0.015). Parathyroid hormone (PTH) level in the upper third of normal range (45–65 ng/L) was observed in 11 (17%) patients. Parathyroid hormone (PTH) was inversely correlated with total calcium intake (r = −0.4, p = 0.001), dairy calcium intake (r = −0.83, p = 0.05), non-dairy calcium intake (r = −0.29, p = 0.043), 25OHD3 serum level (r = −0.3, p = 0.007) and positively correlated with bone turnover markers (deoxypyridinoline crosslinks [DPD], r = 0.36, p = 0.01 and bone specific alkaline phosphatase [BSAP] r = 0.36, p = 0.01). Decrease in quantitative bone parameters compared to age-matched controls was observed in the axial and in the appendicular skeleton in men and in postmenopausal women: mean z-score for LS −0.87 ± 0.22 and −1.32 ± 0.65, p = 0.004 and 0.015, tibia −1.15 ± 0.53 and −0.44 ± 0.044, p < 0.001 and 0.27, phalanx −0.98 ± 0.22 and −0.52 ± 0.98, p < 0.001. We observed decrease in bone mass in patients with serum PTH in the upper tertile of normal range in the FN (z-score −0.57 ± 0.6 versus −0.03 ± 0.9, p = 0.025), TH (−0.51 ± 0.96 versus 0.04 ± 0.9, p = 0.05) and radius (−1.84 ± 0.27 versus −0.07 ± 1.61, p = 0.025, respectively). z-scores in FN and TH positively correlated with serum 25OHD3 level (r = 0.31, 0.29; p = 0.014, 0.019). In postmenopausal women serum 25OHD3 level correlated also with LS z-scores (r = 0.52, p = 0.004); FN and TH z-scores negatively correlated with DPD level (r = −0.51, p = 0.02 and r = −0.55, p = 0.04).Conclusion: LI state may lead to increased bone turnover and decreased bone mass especially in men and postmenopausal women. Impaired vitamin D status and low calcium intake may be deleterious to bone in this condition.

Calciuria in symptom-free primigravid women remote from term: Is the response to an oral calcium challenge predictable?

Objective: This study was undertaken to compare the calciuric response in symptom-free primigravid women to an oral calcium load between those with normal urinary calcium excretions and those with relatively low urinary calcium excretions. Study Design: This was a prospective clinical trial. Eligible primigravid women between 16 and 20 weeks’ gestation provided a 24-hour urine sample for determination of urinary calcium/urinary creatinine ratio. On the basis of these results the patients were divided into 2 groups: a relatively hypocalciuric group, in which the urinary calcium excretion was ≤3.4 mg · kg –1 · 24 h –1, and a normocalciuric group, in which the urinary calcium excretion was >3.4 mg · kg –1 · 24 h –1. All participants undertook a 3-day low calcium dietary regimen. On the fourth day women underwent an oral calcium challenge. A 2-hour urine sample was collected before ingestion of 1 g calcium carbonate (preload). One hour after ingestion the women again collected a 2-hour urine sample (postload). The urinary calcium/urinary creatinine ratios in the preload and postload samples were determined and compared within and between the groups. Results: The mean change (±SD) between the preload and postload urinary calcium/urinary creatinine ratios in the relatively hypocalciuric group was 0.60 ± 1.44 ( P = .04); that in the normocalciuric group was 3.09 ± 2.26 ( P = .11 ). There was a 5-fold difference in the response to calcium load between the hypocalciuric women and the normocalciuric women (0.60 vs 3.09), although this difference was not statistically significant ( P = .20). Conclusions: Both hypocalciuric and normocalciuric women responded to an oral calcium challenge by an increase in the calcium excretion. The cause of the hypocalciuria in women at increased risk for preeclampsia is therefore not simply poor absorption of calcium. (Am J Obstet Gynecol 1999;180:1419-21.)

Metabolic bone disease in primary biliary cirrhosis at presentation

Metabolic bone disease, particularly osteoporosis, is a complication of advanced primary biliary cirrhosis, but the extent of the problem is unclear. We present 33 patients who were investigated for bone disease at the time of diagnosis of their liver disease and who had received no prior treatment likely to influence their bones. Iliac crest bone biopsy showed no patient with osteoporosis, and mild osteomalacic changes in 1 patient. Slight elevations in appositional rate, osteoid volume, and resorption surface were compatible with a state of high bone turnover. Photon absorptiometry revealed a low forearm bone mineral content in 3 of 25 patients, calcium absorption was below normal in 14 of 24 patients, and there was evidence of fat malabsorption in 11 of 25 patients. Five patients also had low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Thus, little evidence of significant metabolic bone disease was found in this group by these methods, but abnormalities were seen, such as poor calcium absorption, that may predispose to its later development.

Vitamin D metabolism in preterm infants.

Perinatal metabolism of vitamin D was studied in premature babies with the aim of: (1) reporting the relationship between the pregnant mother and her preterm infant and the metabolism of vitamin D during the first weeks of life, and (2) assessing the effect of vitamin D metabolites on phosphorus calcium and magnesium intestinal absorption. There was only a positive correlation between plasma cord calcium and 25-hydroxyvitamin D levels and the mother's plasma levels at birth. During the hypocalcemic episode observed during the first week of life, vitamin D activation did occur, but later on rickets or osteomalacia cannot be due to the low levels of vitamin D metabolites in the preterm receiving an adequate dose of vitamin D (1,000-1,200 IU of D2). Calcitriol, the major metabolite of vitamin D, is acting on the intestine and promotes calcium absorption even in very tiny prematures. The pathogenesis of hypomineralization in the preterm infant is due to the low intake of calcium or phosphorus and/or poor absorption of calcium in the case of vitamin D deficiency.

On the requirement of calcium, phosphorus and vitamin D by premature and low birthweight infants.

During recent years the increased survival rate of very low birthweight infants has lead to an increased incidence of rickets and/or osteopenia in these infants. The pathogenesis is multifactorial. From several studies performed under different conditions it can be concluded that the vitamin D requirement of these infants is about 3 times higher than the normal prophylactic dose. Breastfed infants should be supplemented with extra phosphorus and possibly also extra calcium. Infant formulas designed for low birthweight infants should have a calcium content compensating for the initially poor calcium absorption of these infants.