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Concept: Calcium


To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures.

Concepts: Osteoporosis, Bone, Bone fracture, Fracture, Calcium


To determine whether increasing calcium intake from dietary sources affects bone mineral density (BMD) and, if so, whether the effects are similar to those of calcium supplements.

Concepts: Osteoporosis, Bone, Vitamin D, Apatite, Water, Magnesium, Calcium, Calcium carbonate


Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth, whereas invertebrates utilize calcium carbonate in their mineralized organs. In particular, stable amorphous calcium carbonate is found in many crustaceans. Here we report on an unusual, crystalline enamel-like apatite layer found in the mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite their very different thermodynamic stabilities, amorphous calcium carbonate, amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined functional layers in close proximity within the mandible. The softer amorphous minerals are found primarily in the bulk of the mandible whereas apatite, the harder and less soluble mineral, forms a wear-resistant, enamel-like coating of the molar tooth. Our findings suggest a unique case of convergent evolution, where similar functional challenges of mastication led to independent developments of structurally and mechanically similar, apatite-based layers in the teeth of genetically remote phyla: vertebrates and crustaceans.

Concepts: Arthropod, Calcium, Crustacean, Mineral, Calcium carbonate, Teeth, Crayfish, Aragonite


Vitamin D insufficiency in children may have long-term skeletal consequences as vitamin D affects calcium absorption, bone mineralization and bone mass attainment.

Concepts: Osteoporosis, Bone, Vitamin D, Bone density, Density, Skeletal system, Calcium, Dietary mineral


BACKGROUND: Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OH)D3 (Vitamin D) as well as PTH (Parathyroid Hormone) the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. METHODS: In the presented study, we analyse the time course of 25(OH)D3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OH)D3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value <= 0.05 was considered significant. RESULTS: Serum levels of 25(OH)D3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. CONCLUSIONS: The time course of 25(OH)D3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for therapy and the monitoring of fracture healing.

Concepts: Osteoporosis, Bone, Vitamin D, Calcitonin, Bone fracture, Parathyroid hormone, Calcium, Hyperparathyroidism


INTRODUCTION Dyscalcemia is associated with adverse cardiovascular effects. Therapy of heart failure (HF) may change serum calcium by reduction of urinary wasting or increased calcium apposition to bones.  OBJECTIVES Our objectives were to assess the prevalence of dyscalcemia in patients with newly up-titrated HF therapy, to explore clinical and laboratory determinants of abnormal serum calcium levels and to analyze the relation of dyscalcemia to prognosis. PATIENTS AND METHODS In 722 HF patients (age 53 ± 10 years, 13% female, NYHA class III-IV) naïve to HF drugs, we have assessed crude prevalence of serum dyscalcemia and adjusted risk of calcium abnormalities on top of recommended therapy and analysed the association of calcium abnormalities with mortality at 2 years of follow-up. RESULTS During therapy up-titration NYHA class improved in 66.7% patients, in 31.0% did not change and worsened in 2.4%. Hypocalcemia occurred in 166 (23.0%) patients and was more prevalent in patients who became less symptomatic on target HF therapy. ypercalcemia was diagnosed in 63 (8.7%) patients and predominated in those who did not respond to treatment. These findings were independent of kidney function, BMI, HF ethiology, thiazides use, age and sex. Hypercalcemia was associated with more catabolic profile, hemodynamic compromise, inflammation and lower bone mineral density. Lower albumin, higher serum phosphorus, were independently of kidney function significant predictors of hypercalcemia.  Hypocalcemia was associated with less catabolism, higher albumin, lower phosphorus, treatment of thiazides, smoking history. Neither hypocalcemia nor hypercalcemia affected prognosis.  CONCLUSIONS We concluded that serum dyscalcemia is related to response to HF therapy and HF severity on top of treatment. Mild hypocalcemia is associated with clinical improvement and does not worsen HF outcome. Hypercalcemia occurs more frequently in non-responders to therapy, its clinical significance requires further studies.  

Concepts: Kidney, Bone, Vitamin D, Medical statistics, Calcium, Urinary system, Prevalence, Calcium metabolism


Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. Lifestyle Factor Grade Macronutrients  Fat D  Protein C Micronutrients  Calcium A  Vitamin D B  Micronutrients other than calcium and vitamin D D Food Patterns  Dairy B  Fiber C  Fruits and vegetables C  Detriment of cola and caffeinated beverages C Infant Nutrition  Duration of breastfeeding D  Breastfeeding versus formula feeding D  Enriched formula feeding D Adolescent Special Issues  Detriment of oral contraceptives D  Detriment of DMPA injections B  Detriment of alcohol D  Detriment of smoking C Physical Activity and Exercise  Effect on bone mass and density A  Effect on bone structural outcomes B Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one’s genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.

Concepts: Osteoporosis, Bone, Vitamin D, Nutrition, Systematic review, Calcium, Nutrient, Adolescence


Anthropogenic emissions of carbon dioxide (CO2) are causing ocean acidification, lowering seawater aragonite (CaCO3) saturation state (Ωarag), with potentially substantial impacts on marine ecosystems over the 21(st) Century. Calcifying organisms have exhibited reduced calcification under lower saturation state conditions in aquaria. However, the in situ sensitivity of calcifying ecosystems to future ocean acidification remains unknown. Here we assess the community level sensitivity of calcification to local CO2-induced acidification caused by natural respiration in an unperturbed, biodiverse, temperate intertidal ecosystem. We find that on hourly timescales nighttime community calcification is strongly influenced by Ωarag, with greater net calcium carbonate dissolution under more acidic conditions. Daytime calcification however, is not detectably affected by Ωarag. If the short-term sensitivity of community calcification to Ωarag is representative of the long-term sensitivity to ocean acidification, nighttime dissolution in these intertidal ecosystems could more than double by 2050, with significant ecological and economic consequences.

Concepts: Oxygen, Carbon dioxide, Calcium, Ecosystem, Carbon, Calcium carbonate, Calcite, Aragonite


Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1. Vitamin D3 (D3) induced expression of SKN-1 target genes but not canonical targets of XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.

Concepts: Osteoporosis, Vitamin D, Cancer, Senescence, RNA, Calcium, Vitamins, Aging-associated diseases


Iron, potassium, zinc, and other minerals might impact the development of premenstrual syndrome (PMS) through multiple mechanisms, but few studies have evaluated these relations. We conducted a case-control study nested within the prospective Nurses' Health Study II (1991-2001). Participants were free from PMS at baseline. After 10 years, 1,057 women were confirmed as PMS cases and 1,968 as controls. Mineral intake was assessed using food frequency questionnaires completed in 1991, 1995, and 1999. After adjustment for calcium intake and other factors, women in the highest quintile of nonheme iron intake had a relative risk of PMS of 0.64 (95% confidence interval (CI): 0.44, 0.92; P for trend = 0.04) compared with women in the lowest quintile. Women in the highest quintile of potassium intake had a relative risk of 1.46 (95% CI: 0.99, 2.15; P for trend = 0.04) compared with women in the lowest quintile. High intake of zinc from supplements was marginally associated with PMS (for intake of ≥25 mg/day vs. none, relative risk = 0.69, 95% CI: 0.46, 1.02; P for trend = 0.05). Intakes of sodium, magnesium, and manganese were unrelated to PMS risk. These findings suggest that dietary minerals may be useful in preventing PMS. Additional studies are needed to confirm these relations.

Concepts: Epidemiology, Magnesium, Calcium, Dietary mineral, Mineral, Sodium, Potassium, Dietary minerals