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Flashcards in Dietary Calcium Deck (37):
1

Role of calcium in bone health:

A. Most abundant mineral in the body; average adult male contains ~1200-1500 g (1.7% of total body weight); 99% is in the skeleton;
- 0.7 g skeletal calcium turns over each day; bone Ca turns over ~ every 5-6 yr; extracellular Ca turns over 20-30x/day.

B. Metabolism and Homeostasis:
a. Key hormonal regulators that effect Ca Homeostasis are: PTH, 1,25(OH)2D, and Calcitonin; of course many others can play a role, especially at specific times in the life cycle
b. Serum Ca is maintained in a very tight range at all costs
c. Absorption occurs passively in duodenum, jejunum, ileum; Active transport (effected by habitual intake via vitamin D) occurs in the duodenum
a. Enhancers of Absorption: Vitamin D; physiological demand; lactose; Gastric Acidity; protein
b. Impair Absorption: Vitamin D deficiency, Steatorrhea, Oxalic and Phytic Acid, Gastric Alkalinity
d. "Deficiency" acutely is a rare occurrence in adults because of the body's ability to maintain serum levels; with low Ca intakes, however, because maintenance of serum [Ca] is at the expense of bone Ca. Thus development of deficiency is a long-term, “silent” process.

C. Critical times in the life cycle for Ca++ intake:
a. Premature infants: 3rd trimester period of rapid bone mineral accretion; preterm infants at risk for “osteopenia of prematurity”
b. Adolescence: hormonal milieu during puberty favors calcium absorption and bone deposition; ~ 50% of total adult bone mineral mass is accrued during adolescence.
c. After skeletal “maturity,” esp. peri-menopause: associated with relatively high requirements, increased losses, and frequently with low intake
d. Pregnancy and lactation: physiologic responses compensate for increased Ca demand so dietary requirements are not increased
e. Post-Bariatric Surgery

2

Metabolism and Homeostasis of Calcium

a. Key hormonal regulators that effect Ca Homeostasis are: PTH, 1,25(OH)2D, and Calcitonin; of course many others can play a role, especially at specific times in the life cycle

b. Serum Ca is maintained in a very tight range at all costs

c. Absorption occurs passively in duodenum, jejunum, ileum; Active transport (effected by habitual intake via vitamin D) occurs in the duodenum
i. Enhancers of Absorption: Vitamin D; physiological demand; lactose; Gastric Acidity; protein
ii. Impair Absorption: Vitamin D deficiency, Steatorrhea, Oxalic and Phytic Acid, Gastric Alkalinity


d. "Deficiency" acutely is a rare occurrence in adults because of the body's ability to maintain serum levels; with low Ca intakes, however, because maintenance of serum [Ca] is at the expense of bone Ca.
i. Thus development of deficiency is a long-term, “silent” process.

3

Critical times in the life cycle for Ca++ intake:

a. Premature infants: 3rd trimester period of rapid bone mineral accretion; preterm infants at risk for “osteopenia of prematurity”

b. Adolescence: hormonal milieu during puberty favors calcium absorption and bone deposition; ~ 50% of total adult bone mineral mass is accrued during adolescence.

c. After skeletal “maturity,” esp. peri-menopause: associated with relatively high requirements, increased losses, and frequently with low intake

d. Pregnancy and lactation: physiologic responses compensate for increased Ca demand so dietary requirements are not increased

e. Post-Bariatric Surgery

4

Dietary and lifestyle factors that affect bone health

Remember: Genetic/intrinsic factors dominate the determination of bone mineral density (BMD); 60-80% of variance in peak bone mass attributable to heritable factors.

A. Nutritional/dietary factors:
a) Lifetime calcium intake:
- Adolescent females average ~80% of recommended amount (1300 mg/d)
- Adolescence = key time for bone mineral accretion
- Limited ability to adapt to low Ca intake
- Lifetime low intake of dairy products associated with increased osteoporosis
- Optimal calcium intake allows bone density to reach genetic potential

b) Protein intake: increased urinary calcium excretion (in some studies low Ca:protein intake associated with lower bone density); net effect may be negligible, but controversial;

c) Phosphate intake: ? increased PTH, increased bone resorption

d) Vitamin D – critically linked to calcium absorption:
− Status frequently suboptimal, esp in elderly;
− 25(OH)D levels (+) correlated w/ BMD in middle-aged & elderly women
− Target serum 25(OH)D level >30 ng/ml to reap skeletal benefits
e) Vitamin K - co-factor w/ osteocalcin & other bone forming proteins
f) Sodium intake – high Na++ intake increased urine Ca++ excretion
g) Vegetarian diet, w/ high fruit & veg intake (& K+, Mg++ ) associated w/ bone mass preservation, but if diet is low in dairy & high in sodium, not likely to be positive effect
h) Caffeine – increases urine Ca++ excretion (small effect x lifetime)
i) Whole Diet pattern: DASH may have benefits beyond increased Ca intake

B. Behaviors/lifestyle
a) Exercise: weight-bearing;
- muscle mass directly related to bone mass
- Mechano-sensors in bone stimulate osteoblasts
b) Smoking
c) Alcohol - depresses osteoblasts


C. Medications/medical conditions
a) glucocorticoids, immobility, gastrectomy
b) Maintenance of regular menses
b) Chronic illnesses – associated w/ malabsorption, chronic systemic inflammation

5

Dietary and Supplement sources of Calcium

A. Dietary Sources:
Dairy products contribute ~70% of Ca diet in US (slight ↓ past few decades - ↑availability of fortified products?)
Example Food: mg Ca
Milk, 1 cup ~ 300
Yogurt, 8 oz. 350-450
Tofu, 4 oz (processed w/ Ca++) 155
Salmon, canned, w/ bones, 3 oz ~200
Soy milk, fortified, 1 c 295
Collard greens, ckd , 1c 350
Beans, navy, ckd, 1 c 90

B. Supplement Sources:
Ca-Carbonate:
- max elem. Ca++/tablet: 1250 mg = 500 mg elemental Ca++;
- best absorbed w/ meals; has least lead, esp manufactured (vs bone meal, oyster shell, dolomite);
CaCitrate:

6

IV. Strategies to optimize bone density

− Achieve “peak bone mass” when you can – ie, adolescence

− Weight bearing activity

− Maintain good calcium intake over lifetime

− Avoid excessive alcohol and tobacco

− Minimize practices that enhance calcium loss &/or bone resorption

− Maintain healthy diet including other cofactors that support Bone Health
♣ DASH diet: reduction in Na+ not only associated with reduced blood pressure but also with reduced Ca++ excretion and bone turnover.

− Supplement (only) when necessary
♣ Results of meta-analysis supports benefits of calcium supplementation ± Vit D supplementation on fracture reduction and reduced bone loss in subjects > 50 yr.
• Mild caution re Ca supplementation: Ca supplementation (w/o Vit D) associated with increased risk of myocardial infarction

7

Major Minerals:

a. Require intake > 100 mg/day

b. Contribute > 0.01% of body weight
Include:
Calcium Phosphorus
Magnesium Sodium
Potassium Chloride
Sulfur

c. Most abundant mineral: 1200-1500 g

8

Calcium: General Functions

a. Structural functions of extracellular Ca
i. Ca Hydroxyapatite Ca10(PO4)6(OH)2
ii. Bone & teeth (99%)

b. Metabolic functions of extracellular Ca
i. ~1% total extracellular Ca++
ii. Tertiary structure: activate catalytic & mechanical properties
iii. Most common signal transmitter in biology:
-clotting, nerve impulse transmission/relaxation, mediation of hormones, growth factors

9

Ca Homeostasis:Hormones

*Good review slide

a. Decrease in Serum Calcium
↑ PTH :
i. Increase Bone resorption of Ca
ii. Increase Ca reabsorption in ascending loop of henle
-(decrease urinary [Ca])
-Increase Phosphate excretion via kidney
iii. ↑ Vitamin D: Increase Ca intestinal absorption


b. ↑ Serum [Ca]…
i. ↑ Calcitonin---> Deposition of Ca into Bone
ii. Decrease PTH


10

Ca Homeostasis at the GI

a. Calcium is taken by active and passive transport
i. Passive absorption is driven by high concentrations of Ca in the gut, simply diffuse passively though

b. Active Transport happens with low to medium calcium amounts
i. Will need to get Ca into the enterocyte with unique proteins
ii. need important pump proteins on the basolateral side to get Ca to the blood
iii. Active transport happens mostly at the duodenum
iv. Vitamin D is important for active transport


c. When Ca intakes low/moderate – active = major source of Ca – occurs in duodenum VDR highly expressed

d. When Ca intakes high, passive = major source – occurs length intestine mostly in duodenum, jejunum, ileum

11

VDR/VDRE regulation of:
-Intestinal Ca Absorption
-Renal Ca Excretion

a. For the active transport of Ca, Vitamin D is critical
i. Active form of Vitamin D (1,25 OH Vitamin D3) will enter cell and bind to receptor
ii. Active Vit D3 will bind to the VDR, will lead to transcription and building of BDRE

b. This increased transcription leads to:
1. Increased basolateral membrane transport
2. Cystolitic shuttling
3. Apical membrane Export
* These three set of proteins lead to increased duodenum Ca2+ active absorption, also effects the nephron of the kidney

12

Calcium Absorption & Habitual intake

a. Limited “up-regulation” to compensate for low intake
i. 2,000 to 300 mg/day
ii. Absorption Increased from 27 to 37% in 1-2 wks
iii. 540 ---> 111 mg absorbed


b. Ca intake (chronic) is associated w/ Increased bone accretion

13

Calcium Absorption Enhanced by…

Physiological
a. Vitamin D --> synthesis of Ca-transport proteins
b. Increased physiologic demand (Pregnancy/adolescence)

Dietary
a. Gastric acidity: Release from food matrix

b. Lactose (maintains solubility)

c. Dietary protein*: Increased intake assoc w/ increased absorbed Ca

[NOT by bone mineral depletion]

14

Calcium Absorption Impaired by…

Physiological
a. Vitamin D deficiency: northern latitudes, limited skin exposure, dark pigmentation, elderly

b. Steatorrhea: unabsorbed fatty acids bind Ca2+ ---> “soaps”

Dietary
a. Gastric alkalinity: especially gastric achlorhydria in elderly

b. Oxalic acid: ex: spinach

c. Phytic acid : ex: legumes, soy beans, corn, wheat

d. Caffeine: ↑ urine Ca2+ (Easy to offset)

e. Dietary Protein*: Increased urine Ca2+ (net effect neutral/positive)

15

Ca Absorption Through the life cycle

Rates of absoprtion throughout different points of life:
a. Average healthy American Adult ~ 25%

b. Fetus: 80% transfer in 3rd trimester

c. Infants: ~40 - 60% (lactose)

d. Early puberty ~34%

e. Pregnant women ~50%

f. May ↓ in elderly (VD, gastric acidity)

16

Lifestage with ↑ Ca Requirements:
Premature Infants

a. 30g total crosses the placenta
i. during a healthy pregnacy

b. 80% total Ca transfer occurs in 3rd trimester (endochondral bone formation)
i. Critical that infants get plenty of Ca into babies, premature misses out on this time

c. 330 mg/day at 35 weeks

17

Lifestage with ↑ Ca Requirements:
School Age Children

Ca deficient Rickets

a. Rickets is defective mineralization or calcification of bones before epiphyseal closure in immature mammals due to deficiency or impaired metabolism of vitamin D, phosphorus or calcium, potentially leading to fractures and deformity.

b. Rickets is among the most frequent childhood diseases in many developing countries.
i. The predominant cause is a vitamin D deficiency, but lack of adequate calcium in the diet may also lead to rickets (cases of severe diarrhea and vomiting may be the cause of the deficiency).
ii. Although it can occur in adults, the majority of cases occur in children suffering from severe malnutrition, usually resulting from famine or starvation during the early stages of childhood.

c. Osteomalacia is a similar condition occurring in adults, generally due to a deficiency of vitamin D but occurs after epiphyseal closure

18

Question: Does Ca++ (Dairy) intake matter in young children?

YES

a. Framingham Children’s Study
Children 3-5 yr x 12 yr follow-up
Dairy intake ≥ 2 svg/d
Higher BMC
Highest BMC in high dairy and high meat/protein

b. Beneficial effect of childhood dairy consumption on adolescent bone status (Moore, J Peds, 2008)

“…These studies support an increase in skeletal size and mineralization that occurs with Ca supplementation, but fail to show consistently that BMC is retained over the long term, especially if supplementation is withdrawn”.
(DRI, 2011)

“Numerous Observational Studies and RCT’ have shown a favorable effect of dairy products on bone health during childhood and adolescence.”
(Belgian Bone Club and ESCEO, Calcif Tissue Int; 2016)

19

Lifestage with ↑ Ca Requirements: Adolescence

a. 30-50% bone mass accrued during adolescents

b. Shown here is the familiar curve indicating the steep accrual of bone mass that occurs during adolescence. It is commonly appreciated that inadequate lifestyle or dietary factors may slow this bone mass accrual placing women at increased risk for fracture later in life when bone mass begins to diminish, as shown by the dashed line.

c. In fact a recently published study confirmed that women who experienced a pregnancy during adolescence were at increased risk of becoming osteoporotic post-menopause; OR = 2.2

20

Bone Accretion During Adolescence

a. Calcium absorption & retention highest in early puberty

b. Slower bone mineralization occurs throughout adolescence

21

Lifestage with ↑ Ca Requirements:
Pregnancy and Lactation

a. Physiological - but not dietary - requirements increase.

b. Pregnancy: Ca absorption increases (active) to accommodate fetal demand

c. Lactation: PTH ↑ and bone mass lost, but recovered with post-weaning

22

DRI's

a. For adolescents, will have really high DRI for their calcium
i. suggested intakes are increased

b. For elderly, will have higher DRI for Ca intake
i. need it more during this time

23

Where Is Calcium in Food?

a. Milk has an extreme amount of calcium

b. Kale and Tofu has a high amount

c. Calcium is in other foods as well

24

Supplements

1. Calcium carbonate (e.g. TUMS)
i. Maximum elemental Ca/tablet (40%);
ii. 1250 mg = 500 mg Ca
iii. Best absorbed w/ meals (30%)
iv. Least lead

2. Calcium citrate malate
i. 21% elemental Ca
ii. Best absorbed between meals (36%)

43% of Americans (70% of older women) consume Ca supplements

25

Ca Intakes (50th percentile) From Food AND supplements

a. Women are doing worst at having Ca intake than males
i. Women of multiple ages are struggling with Ca intake

b. Only elderly males are concerned in the male population

26

Conclusions of DRI for Ca & Vit D

a. “Overall…the majority of Americans…are receiving adequate amounts of both calcium and Vitamin D…

b. High-risk groups:
i. Premature infants
ii. Adolescents
iii. Peri-menopausal women
iv. Bariatric Surgery

27

Osteoporosis - neck or spine in women > 50 yr

a. Certain populations are at a greater risk for osteoperosis (hispanic woman at greater risk)

b. Genetics lead to this risk drastically

28

Non-Nutritional Factors Associated w/ BMD

a. Initial bone mineral density

b. peak bone mass (PBM)

c. heredity (~ 70 - 80% variability in PBM)

29

Non-Nutritional Factors Associated w/ BMD

a. Initial bone mineral density
i. peak bone mass (PBM)
ii. heredity (~ 70 - 80% variability in PBM)

b. Hypogonadism (esp decreased estrogen)

c. Age – strongest empiric predictor of BMD

d. Medications (esp corticosteroids)
a) glucocorticoids, immobility, gastrectomy
b) Chronic illnesses – associated w/ malabsorption, chronic systemic inflammation;
c) Magnitude of steroid use = single strongest predictor of osteopenia pts w/ inflammatory bowel disease (both ulcerative colitis & Crohn’s disease); obesity

d. Behaviors/lifestyle
i. Tobacco & Alcohol – depress osteoblast activity, impair nutrition
ii. Weight bearing exercise
iii. Muscle mass directly related to bone mass
iv. Mechanosensors on bone regulate (increase) osteocyte and osteoblast activity

30

Nutritional Factors Associated w/ BMD - Ca

a. Lifetime Calcium intake
i. Chronic low intake of Ca++ /dairy assoc w/ decreased BMD

b. Vitamin D: low status/intake assoc w/ decreased Ca absorption
i. diet, race, age, location-->VD status

c. Oxalic acid & phytic acid
i. Caffeine - ↑ urine [Ca++] (Easy to offset)

ii. Protein intake: increased intake assoc w/ increased absorbed Ca & increased urine [Ca++]

iii. Sodium intake: increased intake assoc w/ increased urine [Ca++]
- 23 mg/d for each teaspoon of salt (2.1 g Na+)

iv. Vegetarian diet: high in fruit/veg--> ↓ urine [Ca++]

31

Nutritional Factors Associated w/ BMD – Not Ca

a. Phosphorus: Hydroxyapatite = Ca(PO4)6(OH)2

b. Mg++ deficiency: ( hypoparathyroid)

c. Vitamin C: cofactor in collagen synthesis

d. Vitamin K: cofactor with osteocalcin

e. Vitamin D

32

Diets Associated w/ BMD

DASH = Dietary Approaches to Stop Hypertension

Emphasizes:
Fruits & vegetables
Low-fat dairy
Whole grains
Poultry, fish & nuts

Limit:
Red meat
Sweets & sugar containing beverages
Total & saturated fat

Dietary Na:
3-levels

33

DASH and Bone Health

1. DASH ↑ Diet calcium: 1250 vs 450 mg/d

2. Higher fruit/veg intake (Mg, Vit C)

3. Na+ reduction: Urine Ca+ ↓ dose dependently as diet Na+ ↓

4. DASH  ↓ turnover of bone

5. No BMD data collected …

* DASH may have benefits to long term bone status

34

Can Ca supplements help BMD???

Small benefit to those at-risk - low diet Ca, older, institutionalized, compromised BMD

a. Meta analysis 2007: (Lancet)
i. Examined RCT w/ Ca ± Vit D supplements & risk of fractures & bone loss
Supplements ≥ 1200 mg Ca & ≥ 800 IU Vit D
12% risk reduction in fractures of all types
Reduced rate of bone loss (hip > spine)

b. 2016 Systematic Reviews:
i. Supplemental Ca does result in small acute increases in BMD but these increases are NOT compounded over time (Tai, BMJ, 2016)
ii. Supplemental Ca may be associated with a small and less-robust reduction in fracture risk (Bolland, BMJ, 2016)
2016 Consensus statement of ESCEO and IOF (Osteopor Int; 2016)
Ca + Vit D supplementation can lead to modest reduction in fracture risk

General consensus:
Small benefit to those at-risk - low diet Ca, older, institutionalized, compromised BMD

35

Can Ca supplements be harmful???

MAYBE....
*Dietary Ca has no risk of CV events, maybe high supplements can lead to risk

a. 2010 Meta-analysis (15 trials) to determine if Ca supplements (± Vit D) ↑ risk cardiovascular events (Bolland, BMJ)
i. ↑ risk of MI ~ 30%
ii. marginal ↑’s risk of stroke, death
iii. highest risk if diet Ca high (> median ~800 mg/d)
iv. Dietary Ca not associated w/ ↑ risk

“…Bias and confounding cannot be excluded as explanation for the reported associations” (Heaney, Adv Nutr, 2012)
“Assertions of ↑ CVD risk consequent to Ca supplementation are not convincingly supported by current evidence” (2016 Consensus statement of ESCEO and IOF; Osteopor Int)

36

Summary on Supplements

a. “Ca + VD supplementation is supported for patients at high risk of Ca and VD insufficiency and in those who are receiving treatment of osteoporosis”
(Consensus statement of ESCEO and IOF; Osteopor Int; 2016)

b. Supplement rules of thumb:
i. Try diet/food first
ii. Supplement when necessarily and appropriately
iii. Use your common sense…

37

Take a holistic and lifecycle approach to optimizing bone health

a. Achieve “peak bone mass” when possible
i. Optimize Ca intake and dietary quality throughout childhood, especially adolescence, and in early adulthood

b. Dietary Focus: Ca, Vit D, Vit K, protein, ↓Na … DASH style diet

c. Maintain ovulation/regular menses

d. Weight bearing exercise

e. Avoid: smoking, alcohol, steroids

f. Supplement: judiciously when necessary