calcium, physiology, absorption, renal absorption, deficiency,

1. Calcium – an overview
Vinod Naneria
Choithram Hospital & Research Centre
Indore, India

2. 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

3. 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.

4. Calcium
• Calcium is critical for
• mediating vascular contraction and
vasodilatation,
• muscle function,
• nerve transmission,
• intracellular signalling, and
• hormonal secretion.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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%).

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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

21. 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%.

22. 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.

23. 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.

24. 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%.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

43. 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.

44. 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).

45. 2010
COMMITTEE TO REVIEW DIETARY REFERENCE INTAKES FOR VITAMIN D AND CALCIUM

46. 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.

47. 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.

49. 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.

50. 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.

51. 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.

52. 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.

53. The New York City
health department
began a campaign
to encourage hospitals
to stop handing out
gift containing
free formula,
equipment, &
instruction manuals
for top feed, to
encourage
more mothers
to breast-feed.

54. The American Academy of Peadiatrics recommends breast-feeding
exclusively for 6 months, and continuing it for a year or more.

55. 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.

56. 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.

57. 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,

58. 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.

59. 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).

60. 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.

61. 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.

62. 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.

63. 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.

64. 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.

65. 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.

66. 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.

67. 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.

68. Adults >70 Years of Age
• Bone loss and the resulting osteoporotic
fractures are the predominant bone health
concern for persons >70 years of age.

69. 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.

70. 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.

71. 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.

72. 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.

73. 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.

74. 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.

75. 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.

76. 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.

77. 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.

78. 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.

79. 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.

80. 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.

82. 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.

83. 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.

84. Winter season change in serum 25OHD levels
across age groups

85. 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.

86. 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.

87. 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.

88. 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.

90. 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.

91. 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.

92. 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.

93. 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.

94. 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.

95. 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.

96. 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.

97. 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.

98. 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.

99. 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.

100. 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.

101. 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.

102. 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.

103. 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.

104. 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.

105. 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.

106. 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.

107. 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.

109. 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