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Calcium -  an overview
 

Calcium - an overview

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calcium, physiology, absorption, renal absorption, deficiency,

calcium, physiology, absorption, renal absorption, deficiency,

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  • Breast Milk Is Good for the Brain, Scans Show
    By NICHOLAS BAKALAR
    Using M.R.I. scans, researchers have added to the evidence that breast-feeding leads to increased rates of brain development in infants.
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  • Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study

    BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f228 (Published 13 February 2013)
    Cite this as: BMJ 2013;346:f228
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  • http://www.medscape.com/viewarticle/778718?nlid=27859_1048&src=wnl_edit_dail
    Heartwire
    Calcium Supplements Linked to Mortality Risk in Men, But Not Women
    Michael O’Riordan
    Feb 04, 2013
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  • very good. but we need to put 4-5 slides in the end with conclusions or take home msg. we must stress and emphasize that it is pointless to use vit D as a routine and as a panacea for each and every problem. giving vit d does not help in most of the situations because calcium metabolism is tightly regulated by the body.
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  • Mechanisms of intestinal calcium absorptionFelix Bronner1,2,*Article first published online: 27 NOV 2002DOI: 10.1002/jcb.10330
  • Mechanisms of intestinal calcium absorptionFelix Bronner1,2,*Article first published online: 27 NOV 2002DOI: 10.1002/jcb.10330
  • Mechanisms of intestinal calcium absorptionFelix Bronner1,2,*Article first published online: 27 NOV 2002DOI: 10.1002/jcb.10330
  • Mechanisms of intestinal calcium absorptionFelix Bronner1,2,*Article first published online: 27 NOV 2002DOI: 10.1002/jcb.10330
  • Read more: http://healthland.time.com/2012/06/12/vitamin-d-and-calcium-not-recommended-for-postmenopausal-women-says-u-s-panel/#ixzz21Z4tgQVX
  • Read more: http://healthland.time.com/2012/06/12/vitamin-d-and-calcium-not-recommended-for-postmenopausal-women-says-u-s-panel/#ixzz21Z4tgQVX
  • J Bone Miner Res. 2009 Aug;24(8):1369-79.Does obesity really make the femur stronger? BMD, geometry, and fracture incidence in the women's health initiative-observational study.Beck TJScienceDaily (Mar. 25, 2011Am J Med. 1997 Oct;103(4):274-80.Body size and hip fracture risk in older women: a prospective study. Study of Osteoporotic Fractures Research Group.Ensrud KE,

Calcium -  an overview Calcium - an overview Presentation Transcript

  • Calcium – an overview Vinod NaneriaChoithram Hospital & Research Centre Indore, India
  • Calcium + Phosphate Calcium• 0.1% of total body calcium is in extra cellular fluid.• 1% is intra cellular.• Rest is in the bone. Phosphates• <1% in extracellular fluid• 14/15% is intracellular• 85% is stored in bone
  • Calcium in extracellular fluid• 41% is combined with plasma protein & is non-diffusible.• 9% is combined with anions (phosphate, citrate)• 50% ionised form for free diffusion & responsible for all functions of Calcium.
  • Calcium• Calcium is critical for• mediating vascular contraction and vasodilatation,• muscle function,• nerve transmission,• intracellular signalling, and• hormonal secretion.
  • Calcium• Calcium is a dietary supplement used when the amount of calcium taken in the diet is not enough.• It is usually taken three or four times a day with food or following meals.
  • Dietary calcium 1000mgm.• 350mg absorb through upper GI.• 250mg of this 350mg is excreted in GI by means of GI juices and sloughed mucosa.• 100mgm is available for blood circulation.
  • Dietary calcium 1000mgm.• Daily exchange of calcium in & out of bone is constant at 500mg.• 59% of total diffusible calcium is excreted through glomeruli in to renal tubules.• 90% of this reabsorbs in proximal tubules, loop of Henle &, early distal tubules.
  • Dietary calcium 1000mgm.• 10% remaining calcium absorption is very selective and is dependent on serum calcium level.• When serum calcium is low – absorption is 100%.• When serum calcium is high – no absorption occurs.• The re-absorption in distal tubules is regulated by PTH.• Only 100mg is excreted through kidney.
  • Ca10(PO4)6(OH)2 Calcium Hydroxyapatite• Over 99 percent of total body calcium is found as calcium hydroxyapatite (Ca10[PO4]6[OH]2) in bones and teeth, where it provides hard tissue with its strength.• It is roughly 1kg.
  • Calcium in serum• An injection of soluble calcium rapidly increase serum concentration of calcium, but within 30 – 60 minutes, it comes down to normal level.• A sudden drop in serum calcium rapidly normalises within 30-60 minutes.• Exchangeable calcium in amorphous form is present in bone for rapid exchange.
  • Calcium sources• Total intake of calcium from all sources for persons > 1 year of age ranges from 918 to 1,296 mg/day, depending upon life stage.• An estimated 72 % of calcium comes from milk, cheese and yogurt and from foods to which dairy products have been added.• The remaining calcium comes from vegetables (7%); grains (5%); légumes (4%); fruit (3%); meat, poultry, and fish (3%); eggs (2%); and miscellaneous foods (3%).
  • Calcium Supplements• The most common forms of supplemental calcium are calcium carbonate and calcium citrate. The bioavailability of the calcium in these forms are different.
  • Calcium Supplements• Fewer tablets of calcium carbonate are required to achieve given dose of elemental calcium.• Calcium carbonate provides 40 % elemental calcium, compared with 21% for calcium citrate.• Costs tend to be lower with calcium carbonate than with calcium citrate, and compliance may be higher among patients who do not want to take (or have difficulty swallowing) multiple pills.
  • Calcium Supplements• Calcium carbonate is more often associated with gastrointestinal side effects, including constipation, flatulence, and bloating.• Should be taken with food.• Gastric acid is required for it’s absorption.• Calcium should be taken in divided dosage, as only 30 - 40% absorb from each dose.
  • Calcium Supplements• Calcium citrate is less dependent on stomach acid for absorption and thus can be taken without food.• It is useful for individuals with achlorhydria, inflammatory bowel disease, or absorption disorders or who are taking histamine-2 receptor blockers or proton pump inhibitors; for residents of long-term care facilities where calcium supplements are not given with meals.
  • Calcium Supplements• Calcium can compete or interfere with the absorption of iron, zinc, and magnesium.• For this reason, persons with known deficiencies of these other minerals who require calcium supplementation usually take calcium supplements between meals.
  • Metabolism Of Calcium Absorption• Calcium is absorbed by active transport (transcellularly) and by passive diffusion (paracellularly) across the intestinal mucosa. Active transport of calcium is dependent on the action of calcitriol and the intestinal vitamin D receptor (VDR). This transcellular mechanism is activated by calcitriol and accounts for most of the absorption of calcium at low and moderate intake levels.
  • Metabolism Of Calcium Absorption• Transcellular transport occurs primarily in the duodenum where the VDR is expressed in the highest concentration, and is dependent on up- regulation of the responsive genes including the calcium transport protein called transient receptor potential cation channel, vanilloid family member 6 or TRPV6.• These features—up-regulation of VDR and TRPV6—are most obvious during states in which a high efficiency of calcium absorption is required.
  • Metabolism Of Calcium Absorption• Passive diffusion or paracellular uptake involves the movement of calcium between mucosal cells and is dependent on luminal:serosal electrochemical gradients.• Passive diffusion occurs more readily during higher calcium intakes (i.e., when luminal concentrations are high) and can occur throughout the length of the intestine.• However, the permeability of each intestinal segment determines passive diffusion rates.• The highest diffusion of calcium occurs in the duodenum, jejunum, and ileum.
  • Metabolism Of Calcium Absorption• mean calcium absorption (“fractional calcium absorption,” which is the percentage of a given dose of calcium that is absorbed) in men and non- pregnant women—across a wide age range— has been demonstrated to be approximately 25% of calcium intake.• Mean urinary loss averages 22% and fecal loss 75% of total calcium intake, with minor losses from sweat, skin, hair, etc.• In general, mean calcium absorption and calcium intake are directly related
  • Metabolism Of Calcium Absorption• Fractional calcium absorption varies inversely with calcium intake when the intake is very low.• When calcium intake was lowered from 2,000 to 300 mg, healthy women increased their fractional whole body retention of ingested calcium, an index of calcium absorption, from 27% to about 37%.
  • Metabolism Of Calcium Absorption• This type of adaptation occurs within 1 to 2 weeks and is accompanied by a decline in serum calcium concentration and a rise in serum PTH and calcitriol concentrations.• The fraction of calcium absorbed rises adaptively as intake is lowered. However, this rise is not sufficient to offset the loss in absorbed calcium that occurs as a result of the lower intake of calcium—however modest that decrease may be—and thus net calcium absorption is reduced.
  • Metabolism Of Calcium Absorption• Fractional calcium absorption varies during critical periods of life.• In infancy, it is high at approximately 60%.• Calcium absorption in newborns is largely passive and facilitated by the lactose content of breast milk.• As the neonate ages, passive absorption declines and calcitriol-stimulated active intestinal calcium absorption becomes more important.
  • Metabolism Of Calcium Absorption• In exclusively breast-fed infants on vary low calcium intakes of about 200 mg/ day, absorption fraction ranges above 60%.• Formula-fed infants receiving calcium 900 mg/ day have absorption fraction up to about 30%.
  • Metabolism Of Calcium Absorption• As the infant transitions into childhood, fractional calcium absorption declines, only to rise again in early puberty, a time when modelling of the skeleton is maximal.• Fractional absorption in white girls with a mean calcium intake of about 931 mg/day to average 28% before puberty,• 34% during early puberty (the growth spurt),• 25 percent 2 years after early puberty.• Fractional absorption remains about 25 percent in young adults.
  • Metabolism Of Calcium Absorption• Metabolic status also influences calcium absorption such that severe obesity is associated with higher calcium absorption and dieting reduces the fractional calcium absorption by 5 percent.• With aging and after menopause, fractional calcium absorption has been reported to decline on average by 0.21 percent per year after 40 years of age.
  • Metabolism Of Calcium Absorption• Fractional calcium absorption decreases with age. There is an inverse correlation between age and calcium absorption in women.• Several studies have indicated that despite an increase in circulating levels of calcitriol in older women, which would be anticipated to increase calcium uptake, fractional calcium absorption was unaffected.
  • Metabolism Of Calcium Absorption• Thus, although calcium absorption (active calcium transport) has been reported to decrease with age, it is challenging to take this factor into consideration given that calcium intake must be very high to have a significant effect on calcium uptake via the passive absorption.
  • Paracellular absorption• Concentration and voltage dependence of unidirectional 45Ca transport measurements indicated that approximately 60-70% of the mucosa-to-serosa calcium flux measured across the short-circuited rat duodenum, jejunum and ileum is paracellular, with only 30-40% of the mucosa-to-serosa calcium transport cellular. J Nutr. 1992 Mar;122(3 Suppl):672-7. Paracellular calcium transport across the small intestine. Karbach U.
  • Paracellular absorption• Calcium is absorbed in the mammalian small intestine by two general mechanisms: – a transcellular active transport process, located largely in the duodenum and upper jejunum; – a paracellular, passive process that functions throughout the length of the intestine.
  • Paracellular absorption• The transcellular process involves three major steps: entry across the brush border, mediated by a molecular structure termed CaT1, intracellular diffusion, mediated largely by the cytosolic calcium-binding protein (calbindinD9k or CaBP); and extrusion, mediated largely by the CaATPase.• Chyme travels down the intestinal lumen in ∼3 h, spending only minutes in the duodenum, but over 2 h in the distal half of the small intestine.
  • Paracellular absorption• When calcium intake is low, transcellular calcium transport accounts for a substantial fraction of the absorbed calcium. When calcium intake is high, transcellular transport accounts for only a minor portion of the absorbed calcium, because of the short sojourn time and because CaT1 and CaBP, both rate-limiting, are down regulated when calcium intake is high.
  • Paracellular absorption• Biosynthesis of CaBP is fully and CaT1 function is approximately 90% vitamin D-dependent. At high calcium intakes CaT1 and CaBP are downregulated because 1,25(OH)2D3, the active vitamin D metabolite, is down regulated.
  • Regulation of D3 & 25(HO)D3• Not all 7dehydrocholesterol get converted into Cholecalciferol in the skin.• Not all D3 (Cholecalciferol) get converted in to 25(HO)D3.• It is a tightly controlled conversion• D3 can be stored in liver and fat for months together.
  • Regulation of D3 & 25(HO)D3• 25(HO)D3 can remain in blood for 15 days.• D3 may increase to many fold but 25(HO)D3 level is may remain normal.• This mechanism save D3 in the body for future use.• 1,25,(HO)2D3 have biological life of 15 hours.
  • Regulation of 1,25(HO)2 D3• Inversely proportional to serum calcium level.• Less calcium - more synthesis of 1,25(HO)2D3• More calcium - less synthesis of 1,25(HO)2D3• This is under the control of PTH.• ↓ Calcium → ↑PTH → ↑1,25(HO)2D3• ↑ Calcium → ↓ PTH → ↓1,25(HO)2D3• ↑ Calcium → ↓ PTH → ↑ 24,25(HO)2D3
  • Renal handling of Calcium• Calcium is filtered at the glomerulus, with the ultra filterable fraction of plasma Ca entering the proximal tubule .• Within the proximal convoluted tubule and the proximal straight tubule, isosmotic reabsorption of Ca occurs such that at the end of the PST the UFCa to TFCa ratio is about 1.1 and 60% to 70% of the filtered Ca has been reabsorbed.
  • Renal handling of Calcium• Passive paracellular pathways account for about 80% of Ca reabsorption in this segment of the nephron, with the remaining 20% dependent on active transcellular Ca movement.• No reabsorption of Ca occurs within the thin segment of the loop of Henle.• Ca is reabsorbed in small amounts within the medullary segment of the thick ascending limb (MAL) of the loop of Henle and calcitonin (CT) stimulates Ca reabsorption here.
  • Renal handling of Calcium• However, the cortical segments reabsorb about 20% of the initially filtered load of Ca.• Under normal conditions, most of the Ca reabsorption in the cTAL is passive and paracellular, owing to the favorable electrochemical gradient.• Active transcellular Ca transport can be stimulated by both parathyroid hormone and 1,25-dihydroxy-vitamin D3 in the cTAL.
  • Renal handling of Calcium• In the early distal convoluted tubule (DCT), thiazide-activated Ca transport occurs. The DCT is the primary site in the nephron at which Ca reabsorption is regulated by PTH and 1,25(OH)2D3.• Active transcellular Ca transport must account for Ca reabsorption in the DCT, because the transepithelial voltage becomes negative, which would not favor passive movement of Ca out of the tubular lumen.
  • Renal handling of Calcium• About 10% of the filtered Ca is reabsorbed in the DCT, with another 3% to 10% of filtered Ca reabsorbed in the connecting tubule (CNT) by way of mechanisms similar to those in the DCT. ATPase—adenosine triphosphatase; CaBP-D—Cabinding protein D; DT—distal tubule; VDR—vitamin D receptor.
  • Mechanism of action of 1,25(HO)2 D3• ↑ Calcium binding protein in the mucosal cells of intestine.• CBP actively transport Calcium from mucosa to blood.• The calcium absorption is directly proportional to the quantity of CBP.• CBP remains in the cells for many weeks, causing prolonged effect of calcium absorption.• Increases calcium absorption from renal tubules.
  • Mechanism of action of 1,25(HO)2 D3• Administration of extreme quantity of D3 causes absorption of bone.• In the absence of D3, the effect of PTH on bone absorption is markedly reduced.• Vit D3 in small quantity promotes bone calcification. (↑ intestinal absorption, & enhancement of calcium mobilization through cell membrane – during osteoclastic activity).
  • 2010COMMITTEE TO REVIEW DIETARY REFERENCE INTAKES FOR VITAMIN D AND CALCIUM
  • IOM – Recommended Dietary indexes• The DRIs established in this report are based on the current understanding of the biological needs for calcium and vitamin D across the North American population.
  • DRI• In vitamin D–deficient states with minimal calcium intake, absorption of calcium from the gut cannot be enhanced.• No amount of vitamin D is able to compensate for inadequate total calcium intake.• DRI value for vitamin D setting requires that calcium is available in the diet in adequate amounts.
  • Calcium: Dietary Reference Intakes For Adequacy• Infants 0 to 6 Months AI 200 mg/day Calcium• Infants 6 to 12 Months AI 260 mg/day Calcium• Human milk is recognized as the optimal source of nourishment for infants There are no reports of any full-term, vitamin D–replete infants developing calcium deficiency when exclusively fed human milk.
  • Breast feed• A infant consume 780 mL/day average amount of breast milk. The average level of calcium within a litre of breast milk is 259 mg (± 59 mg). It is therefore estimated that the intake of calcium for infants fed exclusively human milk is 202 mg/day. This number is rounded to 200 mg/day.
  • Breast feed• Calcium absorption for this age group is around 60% depending upon the total amount of calcium consumed.• The usual accretion rate for calcium in infants is estimated at 100 mg/day overall during the first year of life.• The expected net retention of calcium from human milk assuming 60 percent absorption would be 120 mg/day.
  • Breast feed• human milk–fed infants, the mean calcium intake was 327 mg/day, and calcium retention was 172 mg/day on average (Fomon and Nelson, 1993).• If infants consume calcium at the AI daily, they would achieve similar or greater calcium retention even if the efficiency of absorption was at the lower observed value of 30 percent.
  • The New York Cityhealth department began a campaignto encourage hospitalsto stop handing outgift containingfree formula,equipment, &instruction manualsfor top feed, toencouragemore mothersto breast-feed.
  • The American Academy of Peadiatrics recommends breast-feedingexclusively for 6 months, and continuing it for a year or more.
  • Children and Adolescents 1 Through 18 Years of Age• Children 1 - 3 Years EAR 500 mg/day Calcium RDA 700 mg/day Calcium.• Children 4 - 8 Years EAR 800 mg/day Calcium RDA 1,000 mg/day Calcium.• Children 9 - 18 Years EAR 1,100 mg/day Calcium RDA 1,300 mg/day Calcium.• The focus is the level of calcium intake consistent with bone accretion and positive calcium balance.
  • Adults 19 Through 50 Years of Age• EAR 800 mg/day Calcium• RDA 1,000 mg/day Calcium• While there is evidence of minor bone accretion into early adulthood, the levels required to achieve this accretion—which appears to be site dependent—are very low.• The goal, therefore, is intakes of calcium that promote bone maintenance and neutral calcium balance.
  • Adults 19 Through 50 Years of Age• There is no evidence that intakes of calcium higher this offer benefit for bone health in the context of bone maintenance for adults 19 to 50 years of age.• Osteoporotic fracture is not a relevant measure for this life stage,
  • Adults 51 Years of Age and Older• Men 51 - 70 Years of Age EAR 800 mg/day Calcium RDA 1,000 mg/day Calcium• Women 51 - 70 Years of Age EAR 1,000 mg/day Calcium RDA 1,200 mg/day Calcium• Adults >70 Years of Age EAR 1,000 mg/day Calcium RDA 1,200 mg/day Calcium The goal of calcium intake during these life stages is to lessen the degree of bone loss. calcium intake at any level is not known to prevent bone loss.
  • Adults 51 Years of Age and Older• Calcium absorption (active calcium transport) has been reported to decrease with age, it is challenging to consider higher calcium intake as a remedy given that calcium intake must be extremely high to have an effect on calcium uptake via passive absorption ( paracellular transport).
  • Adults 51 Years of Age and Older• Cross–sectional data suggest that, overall, the rate of bone loss in men is substantially slower than that in women, and men have a lower incidence of fractures.• National Osteoporosis Foundation have issued guidelines that do not stipulate BMD testing for men until the age of 70 years (NOF, 2008), whereas they recommend BMD testing at an earlier age for women.
  • Adults 51 Years of Age and Older• Women 51 through 70 years of age are considered separately from men. Although calcium intake does not prevent bone less during the first few years of menopause, there is the question of whether or to what extent calcium intake can mitigate the loss of bone during and immediately following the onset of menopause.
  • Adults 51 Years of Age and Older• Absolute hip fracture rates are lower than for women in this age range than for women over the age 70 but still greater than for premenopausal women. Moreover, BMD is a reliable predictor for fracture risk later in life and therefore becomes a useful measure for DRI purposes.
  • Vitamin D and Calcium: Not Recommended for Postmenopausal Women• The U.S. Preventive Services Task Force (USPSTF) based its draft recommendation — available for public comment until July 10 — on a recent review of the latest research, which found that taking daily supplements of 400 IU of vitamin D combined with 1,000 mg of calcium did little to reduce the risk of bone fracture in healthy postmenopausal women.
  • Vitamin D and Calcium: Not Recommended for Postmenopausal Women• The evidence also suggested that low-dose supplementation slightly increased the risk of kidney stones, and therefore confers “no net benefit” for the prevention of fractures.• The panel said there wasn’t adequate evidence on the benefits of higher daily doses of vitamin D and calcium to make a recommendation either way. It also found insufficient evidence to determine whether the supplements had any effect on users’ cancer risk.
  • Women’s Health Initiative trial• Evidence from the (WHI) conducted using 36,282 women ages 50 to 79 years indicated that participants who were randomized to 1,000 mg of calcium plus 400 International Units of vitamin D per day experienced a small, but significant, improvement in hip bone density and a modest reduction in hip fractures, although the change in hip fracture risk was not statistically significant.
  • Women’s Health Initiative trial• It would appear that the life stage consisting of women 51 through 70 years of age reflects a diverse set of physiological conditions—notably premenopausal, perimenopausal, and postmenopausal—with respect to the condition of bone health, and cannot be reliably characterized as a homogeneous single group for the purpose of deriving EARs and RDAs for calcium. Some may benefit from increased calcium, and some may not.
  • Women’s Health Initiative trial• Therefore, to ensure public health protection and to err on the side of caution, preference is given to covering the apparent benefit for BMD with higher intakes of calcium for postmenopausal women within this group. The EAR for women 51 through 70 years is set at 1,000 mg calcium per day.
  • Adults >70 Years of Age• Bone loss and the resulting osteoporotic fractures are the predominant bone health concern for persons >70 years of age.
  • Pregnancy• The EAR for non-pregnant women and adolescents is appropriate for pregnant women and adolescents based on the randomized controlled trials (RCTs) of calcium supplementation during pregnancy that reveal no evidence that additional calcium intake beyond normal non-pregnant requirements has any benefit to mother or fetus.
  • Pregnancy• Consistent with the RCT data indicating the appropriateness of the non-pregnant EAR and RDA for the pregnant woman is the epidemiologic evidence suggesting that parity is associated with a neutral or even a protective effect relative to maternal BMD or fracture risk.
  • Pregnancy• The physiologic evidence that maternal calcium needs are met through key changes resulting in a doubling of the intestinal fractional calcium absorption, which compensates for the increased calcium transferred to the fetus (200 to 250 mg/day) and potentially some transient mobilization of maternal bone mineral, particularly in the late third trimester.
  • Pregnancy• Overall, it appears that pregnant adolescents make the same adaptations as pregnant women, and there is no evidence of adverse effects of pregnancy on BMD measures among adolescents.• The EARs are thus 800 mg/day for pregnant women and 1,100 mg/day for pregnant adolescents.• Likewise, the RDA values for non-pregnant women and adolescents are applicable, providing RDAs of 1,000 mg/day and 1,300 mg/day, respectively.
  • Lactation• The EAR for non-lactating women and adolescents is appropriate for lactating women and adolescents based on the strong evidence of physiologic changes resulting in a transient maternal bone resorption to provide the infant with calcium.
  • Lactation• Evidence from RCTs and observational studies that increased total calcium intake does not suppress this maternal bone resorption or alter the calcium content of human milk.• Post-lactation maternal bone mineral is restored without consistent evidence that higher calcium intake is required, as based on two RCTs and several observational studies.
  • Lactation• Adolescents, like adults, reabsorb bone during lactation and recover fully afterward with no evidence that lactation impairs achievement of peak bone mass.• The EARs are thus 800 for lactating women and 1,100 mg/day for lactating adolescents. Likewise, the RDA values for non-lactating women and adolescents are applicable, providing RDAs of 1,000 and 1,300 mg/ day, respectively.
  • Vitamin D: Dietary Reference Intakes For Adequacy• A dose–response relationship between vitamin D intake and bone health is lacking. Rather, measures of serum 25OHD levels as a biomarker of exposure (i.e., intake) are more prevalent.
  • Conclusions Regarding Data for 25OHD and Bone Health Calcium absorption• Given that an identified key role of vitamin D is to enhance calcium absorption, evidence regarding the level of serum 25OHD associated with maximal calcium absorption is relevant to establishing a dose–response relationship for serum 25OHD level and bone health outcomes.• Both children and adults there was a trend toward maximal calcium absorption between serum 25OHD levels of 30 and 50 nmol/L, with no clear evidence of further benefit above 50 nmol/L.
  • Rickets• In the face of adequate calcium, the risk of rickets increases below a serum 25OHD level of 30 nmol/L and is minimal when serum 25OHD levels range between 30 and 50 nmol/L. Moreover, when calcium intakes are inadequate, vitamin D supplementation to the point of serum 25OHD concentrations up to and beyond 75 nmol/L has no effect.
  • Osteomalacia from post-mortem observational study• Evidence indicated that even relatively low serum 25OHD levels were not associated with the specified measures of osteomalacia, mostly likely owing to the impact of calcium intake.• This is consistent with a number of studies, both from trials and from observational work, indicating that vitamin D alone appears to have little effect on bone health outcomes; it is most effective when coupled with calcium.
  • 25OHD levels below 30 nmol/L• outcomes: increased risk of rickets, impaired fractional calcium absorption, and decreased bone mineral content (BMC) in children and adolescents; increased risk of osteomalacia and impaired fetal skeletal outcomes; impaired fractional calcium absorption and an increased risk of osteomalacia in young and middle-aged adults; and impaired fractional calcium absorption and fracture risk in older adults.
  • Inter-relationship between calcium and vitamin D• At lower levels of vitamin D, there appears to be a compensation on the part of calcium, and calcium intake can overcome the marginal levels of vitamin D.• Calcium appears to be the more critical nutrient in the case of bone health, and therefore has an impact the dose– response relationship.• Therefore, calcium or lack thereof may “drive” the need for vitamin D.
  • Inter-relationship between calcium and vitamin D• Overall data suggest that 50 nmol/L can be set as the serum 25OHD level that coincides with the level that would cover the needs of 97.5 percent of the population. The serum 25OHD level of 40 nmol/L serum 25OHD is consistent with the median requirement. The lower end of the requirement range is consistent with 30 nmol/L, and deficiency symptoms may appear at levels less than 30 nmol/L depending upon a range of factors.
  • Winter season change in serum 25OHD levels across age groups
  • Inter-relationship between calcium and vitamin D• In one study where participants started the season with lower baseline serum 25OHD levels (i.e., 36 nmol/L), the concentrations decreased only slightly (i.e., to 34 nmol/L).• In other studies where participants began the season with higher baseline serum 25OHD levels (i.e., 57 to 66 nmol/L, respectively) the serum 25OHD levels decreased more (i.e., to 34 and 43 nmol/L, respectively), compared with those participants with lower baseline levels.• In short, the decline in serum 25OHD levels in the placebo arm of these studies appears to be greatest when initial serum 25OHD levels are higher.
  • Inter-relationship between calcium and vitamin D• The kinetics of vitamin D turnover or mobilization from stores may differ in those who have lower baseline serum 25OHD levels.• There is a steeper rise in serum 25OHD levels when vitamin D dosing is less than 1,000 IU/day of vitamin D.• A slower, more flattened response is seen when doses of 1,000 IU/day or higher are administered.
  • Inter-relationship between calcium and vitamin D• In short, regardless of baseline intakes or serum 25OHD levels, under conditions of dosing the increment in serum 25OHD above baseline differs depending upon whether the dose was above or below 1,000 IU/ day.
  • Adiposity• Excess adiposity or obesity—defined as a body mass index (BMI) measure of 30 mg/m2 or higher—is associated with lower serum 25OHD concentrations (and higher parathyroid hormone levels) than found in non-obese counterparts. It is due of 25OHD by adipose tissue.
  • Adiposity• A modest weight loss have found circulating 25OHD levels to increase despite no increased intake of vitamin D from diet or sun exposure, suggesting release from adipose stores with adipose depletion.• Further, neither season nor ethnicity influences these biochemical parameters.
  • Adiposity• The combined influence of increased weight- bearing activity and endogenous synthesis of estrogen due to outcomes of increased adiposity has long been associated with higher bone density.
  • Adiposity• In a population-based study in Finland of perimenopausal and early postmenopausal women, it was found that increased body weight was a strong predictor of high bone density.• Likewise, in a retrospective cohort study, found a strong correlation between higher BMI category and high bone density in postmenopausal women.
  • Adiposity• Traumatic forces increase with body weight, but fracture rates at the hip and central body were less frequent with increasing BMI, possibly because of greater soft tissue padding.• Fractures of the wrist, hip and pelvis were significantly less common obese women, When compared to non-obese women.• Older women with smaller body size are at increased risk of hip fracture. This effect is because of lower hip BMD in women with smaller body size.
  • Obesity paradox• Refers to the unexpected findings that obese subjects seem to fare better than, or at least as well as, their normal- or low-weight counterparts in terms of mortality rates in the context of conditions, such as coronary artery disease in hypertensive subjects, congestive heart failure, chronic kidney disease, hemodialysis, postcoronary revascularization, and some instances of non-ST segment elevation in myocardial infarction.
  • Persons Living at Upper Latitudes in North America• The prevailing assumption about the effect of latitude is that ultraviolet B (UVB) penetration decreases with increasing latitude (i.e., distance from the equator) and this, in turn, causes persons living at higher latitudes in North America to experience little or no UVB exposure, making them at risk for vitamin D deficiency.
  • Latitude - Factors• Reduced atmosphere at the poles (about 50% less than at the equator),• More cloud cover at the equator than at the poles,• Differences in ozone cover,• Duration of sunlight in summer versus winter.• UVB penetration over 24 hours during the summer months at Canadian north latitudes equals or exceeds UVB penetration at the equator.
  • Latitude - Factors• Persons living in the northern latitudes are not necessarily receiving notably less total sunlight during the year.• There may be considerable opportunity during the spring, summer, and fall months in the far north for humans to form vitamin D and store it in liver and fat.• Animals living in the same region that are consumed as part of the traditional diet are also rich sources of vitamin D.
  • Latitude - Factors• These factors help to explain why latitude alone does not appear to predict serum 25OHD concentrations in humans.• In a Finnish study, healthy subjects living above the Arctic Circle (latitude 66°N) did not have lower serum 25OHD levels than subjects living in southern Finland; in fact, the group living above the Arctic Circle had higher levels.
  • Persons Experiencing Reduced Vitamin D Synthesis from Sun Exposure• A number of reports through the years have indicated consistently lower serum 25OHD levels in persons identified as black compared with those identified as white.
  • Persons Experiencing Reduced Vitamin D Synthesis from Sun Exposure• The National Health and Nutrition Examination Surveys (NHANES) 2000 to 2004, reported lower serum 25OHD levels for non- Hispanic blacks compared with Mexican Americans and whites. Mexican Americans had serum 25OHD concentrations that were intermediate between those of non-Hispanic blacks and whites.
  • Dark skin• The question is whether the consistently lower levels of serum 25OHD for persons with dark skin pigmentation have significant health consequences.• Tanning indicate Melanin synthesis – as a proof of enough sun exposure for synthesis of vitamin D.
  • Dark-skinned, exclusively breast-fed infants In 2000, a report was published• concerning rickets among nine children from various areas of the United States (Shah et al., 2000). Eight children were described as African American, and one child was described as Hispanic. All patients were primarily breast- fed for more than 11 months, with minimal intake of dairy products and without vitamin D supplementation. Breast milk, is of course, not a source of vitamin D for infants.
  • Use of Sunscreen• Sunscreen absorbs ultraviolet light and prevents it from reaching the skin. It has been reported that sunscreen with a sun protection factor (SPF) of 8 based on the UVB spectrum can decrease vitamin D synthetic capacity by 95 percent, whereas sunscreen with an SPF of 15 can reduce synthetic capacity by 98 percent.
  • Indoor Environments and Institutionalized Older Persons• Increased urbanization and the normative condition among North Americans to work and recreate indoors cannot be quantified or addressed in terms of increased risk for vitamin D deficiency.• Data for institutionalized, frail older persons suggest a propensity for lower serum 25OHD levels generally.
  • Indoor Environments and Institutionalized Older Persons• Restriction to primarily indoor environments inadequate total intake overall.• Aging skin is known to be less effective in synthesizing vitamin D in part because of a decrease in skin provitamin D (7- dehydrocholesterol) levels and in part because of alterations in skin morphology.
  • Alternative Diets or Changes in Dietary Patterns• American Dietetic Association (American Dietetic Association and Dieticians of Canada, 2003; Craig and Mangels, 2009) as well as the Dietitians of Canada (American Dietetic Association and Dietitians of Canada, 2003), appropriately planned vegetarian diets, including total vegetarian or vegan diets, are healthful and nutritionally adequate.
  • Alternative Diets or Changes in Dietary Patterns• low-oxalate vegetables (e.g., kale, bok choy, Chinese cabbage, broccoli, and collards), calcium-containing tofu, or fortified plant- based foods, such as cereals or fruit juice are feasible strategies to ensure adequate intakes of highly bioavailable calcium. Finally, supplements of calcium are also a strategy, although care should be taken not to over- supplement.
  • DISCLAIMER• Information contained and transmitted by this presentation is based on review of literature from internet and form Institute of Medicine summary on DRI for Vitamin D & Calcium.• It is intended for use only by the students of orthopaedic surgery.• Many Gif/Jpeg files are taken from Internet/Textbooks.• Views and opinion expressed in this presentation are personal.• For any confusion please contact the sole author for clarification.• Every body is allowed to copy or download and use the material best suited to him.• There is No financial involvement in preparation of this PPT.• For any correction or suggestion please contact naneria@yahoo.com