Think of it this way: Calcium is ingested through the gut (get more Ca++ into system) Calcium is secreted out of the body through the urine and the feces Calcium is stored in the bones To understand how calcium regulation occurs at the bone, we need to understand how bones work…
Two processes: bone formation and bone resorption, going on continuously Calcium phospate crystals called ‘hydroxyapatite’ surface of crystals can exchange Ca++ and phosphate ions with extracellular fluid Write on board: -osteoblasts: builds bone (takes up Ca++ into bone) -osteoclasts: breaks down bone (removes Ca++ from bone) Now that we understand how calcium cycling happens at the bone, we can go back to the overall picture
CALCITONIN (CT) -Secreted from the C-cells in the thyroid gland -Lowers Ca++ in blood -Promotes deposition of Ca++ into bone -actually inhibits bone resorption in osteoclasts (ask them what osteoclasts do) -control of secretion: -increased plasma Ca++ stimulates C-cells to synthesize and release CT -Ca++ receptor on the cell membrane (draw on board!!) -when Ca++ binds the extracellular domain, activates Gs protein—Adenylate Cyc--increasing Camp -CT action needed -after meals, to prevent post-prandial hypercalcemia -gastrin (secreted in response to food in the stomach) also stimulates CT secretion -CT also important during pregnancy and lactation, to protect mother from Ca++ demands of fetus
PARATHORMONE (PTH) -secreted from cells of the parathyroid glands (chief cells) -increases Ca++ in the blood -remove the gland, plama Ca++ levels plummet, tetanic convulsions and death result -increases Ca++ resorption from the bone (how could it do that?) -stimulates the osteoclasts -increases the number of osteoclasts -increases Ca++ resorption from the pre-urine filtrate in the nephron (draw this!) -Control of secretion: -low extracellular Ca++ causes PTH release -Similar Ca++ receptor as found with CT (how does this work?) -except, when bound by Ca++, activates Gi protein, inhibiting cAMP levels, which decreases PTH secretion -PTH action needed for fine control of plasma Ca++ levels
Define osteoblasts (builders) and osteoclasts (resorbers) again Calcitonin Parathormone Vit D3 Other hormonal regulators of Ca++ homeostasis: Estrogens -stimulate osteoblast activity , limits osteoclast activity, and enhance PTH secretion -although there is a lot of disagreement on what estrogens do exactly in bone
-estrogens changes the set point of PTH cells in the parathyroid so a greater reduction of Ca++ is needed to increase PTH secretion (so E2 decreases Ca++ loss from bones)
Clinical aspects: -(there are not many clinical problems with Ca++, because it rapidly leads to death) -Osteoporosis: decalcification and loss of bone matrix from the skeleton -maximum bone mass is achieved in women at age 35 -in the 30 years after menopause, women lose 30-50% of their bone mass -more common in women than men, may be because women have smaller bone calcium reserves -treatment: -estrogen replacement -increased Ca++ in the diet (slow down Ca++ turnover from bone) -exercise (especially weight bearing activities) stimulates bone deposition raquet arm of tennis players is 35% more dense than other arm
Regulation of serum calcium homeostasis. Serum calcium homeostasis is regulated by a rapid negative feedback hormonal pathway involving the concentration of ionized calcium in serum (Ca, green arrows) and the secretion of parathyroid hormone (PTH, blue arrows) from the parathyroid. A fall in serum calcium (2 Ca) inactivates the calcium receptor in the parathyroid cell (CaR; green circle) and increases PTH secretion (1 PTH), which restores serum calcium (1 Ca) by activating the parathyroid receptor (PTHR; blue circles) in bone, to increase calcium resorption, and in kidney, to increase tubular calcium reabsorption. In kidney, the increased PTH secretion augments its calcium-restorative effect by increasing secretion of 1,25-dihydroxyvitamin D (1,25D; red arrows), which, acting on the vitamin D receptor (VDR, red circles) in gut, increases active calcium absorption and increases calcium resorption in bone.
The Importance of Calcium
• Aids in building strong bones and
• Prevention of osteoporosis
• Essential in the clotting of blood
• Aids nerves in sending messages
• Aids in the contraction of muscles
Skeletal roles of calcium
• Provides structural integrity of skeleton
Calcium is the substrate for bone mineralisation
Skeletal mass cannot be built or maintained if calcium intake
is insufficient or calcium losses are excessive
• Bone is the reservoir for calcium and replenishes extracellular
fluid (ECF) losses
• Calcium plays a role in muscular, neural and most metabolic
Med J Aust 2005; 182: 281-285
Calcif Tissue Int 2002; 70: 70-73. 2.
Medicine Today 2005; 6: 43-50.
1000 g Ca++
stored in bone
lost in urine
calcium lost in feces
Calcium cycling in bone tissue
• Bone formation
• Synthesize a collagen matrix that holds
Calcium Phospate in crystallized form
• Once surrounded by bone, become
• Bone resorption
• Change local pH, causing Ca++ and
phosphate to dissolve from crystals into
• Secreted from the C cells in
• Lowers Ca++ in blood
• Promotes deposition of Ca++
into bone (inhibits osteoclasts)
• Control of secretion from ccells:
• Increases Ca++ in blood
• Increases Ca++ resorption from the bone
– Stimulates osteoclasts
– Increases number of osteoclasts
• Increases Ca++ resorption from nephron
• Necessary for fine control of Ca++ plasma
• Calcitonin (CT)
– Lowers Ca++ in the blood
– Inhibits osteoclasts
• Parathormone (PTH)
– Increases Ca++ in the blood
– Stimulates osteoclasts
• 1,25 Vitamin D3
– Increases Ca++ in the blood
– Increase Ca++ uptake from the gut
– Stimulates osteoclasts
1,25 Vit. D3 (+)
1,25 Vit D3
Activation of vitamin D3
- Cholecalciferol formed
in the skin by sun
- Converted in liver
- 1,25 DHCC formation in
Controlled by PTH
Relationship between calcium intake and calcium absorption /excretion
Calcium dietary intake
700 – 1000 mg/d
Plasma & ECF
9.0 – 10.5
GH, PO4, Sex hormones,
at intake of
~1000 mg/ day
450 – 900 mg/d
100 – 300 mg/d
FAO/WHO expert consultation on human vitamin and mineral
requirements, Update March 2002; HP Kruse, Grundzüge der
Osteologie, Springer Verlag 1984
Regulation of serum calcium homeostasis
Clin J Am Soc Nephrol 5: S23–S30, 2010
Calcium Demands in Pregnancy
Numerous hormones are
involved in calcium homeostasis:
1, 25-dihydroxyvitamin D (1,25-(OH)2D)
Parathyroid hormone (PTH)
Meeting Fetal Calcium Demands
? BONE DENSITY
Maternal Changes in Bone During
Findings in healthy populations:
No. of Longitudinal Studies
Decrease in bone density
2-4 % loss
Increase in bone density
No change in bone density
Difficulties with previous studies:
Final bone measurements are made up to 6 mo postpartum – a time
when lactation induced bone changes have already occurred.
Small sample sizes
Few studies have measurements throughout pregnancy due to
radiation exposure to DXA.
Role of Calcium in Pregnancy
• Calcium decreases risk of hypertension, pre-eclampsia,
low birth weight, and chronic hypertension in children
• Recommended for high risk women with low calcium
intake, if pre-eclampsia is important in the population
• Calcium has other health benefits not related to
Maintaining bone strength
Proper muscle contraction
Cell membrane function
Role of Calcium Pregnancy: Implications
• Involved in mineralization of bones and teeth, energy and
cell production and electrolyte acid-base buffering.
• Fetal bone and teeth calcification primarily occurs in last 2-3
• If calcium levels are too low, demineraliztion of mothers
bones and teeth may occur.
• 4 c milk daily or equivalent to supply 1200 mg calcium daily
Calcium Supplementation in Pregnancy
• Association between reduction in pregnancy induced
hypertension (PIH) and calcium supplementation.
– Reduction of incidence of PIH.
– Routine supplementation likely to be beneficial in women at high
risk of developing PIH or have low dietary calcium intake
– High calcium doses (2 g/day) not associated with adverse events.
– Need adequately sized and designed trials in different settings to
confirm beneficial effects.
• Ca is recommended through diet in women at risk of
hypertension or low calcium areas.
Bucher et al 1996; Kulier et al 1998; Lopez-Jaramillo et al 1997.
Calcium Supplementation in Pregnancy…
• Meta analysis of randomized controlled trials regarding– Mothers: hypertension +/- proteinuria, maternal death
or serious morbidity, abruptio placetae, caesarean
section, length of stay
– Newborns: Preterm delivery, low birth weight/small for
gestational age, neonatal intensive care unit admission,
length of stay, still birth/death, disability, hypertension
Atallah, Hofmeyr and Duley 2000.
• Less hypertension: RR 0.81 (0.74–0.89).
• Less pre-eclampsia: RR 0.70 (0.58–0.83).
• Better if low calcium intake, high risk.
– Low birth weight: RR 0.83 (0.71–0.98), best for women
at highest risk.
– Chronic hypertension: RR 0.59 (0.39–0.91).
– No difference in preterm delivery, neonatal intensive
care unit admission, stillbirth, death.
Atallah, Hofmeyr and Duley 2000.
Specific Causes of Nutritional Calcium
Deficiency in children
• Early weaning( breast milk and formula are excellent source of calcium)
• Diet with low calcium content( <200 mg/day)
• Diet with high phytate, oxalate, phosphate( due to reliance on green leafy
vegetables decreased absorption of dietary calcium)
• Children with unconventional diet (children with milk allergy)
• Transition from formula or breast milk to juice, soda, calcium poor soy milk
without alternative source of dietary calcium
• IV nutrition without adequate calcium
• Calcium malabsorption- celiac disease, intestinal abetalipoproteinemia, small
Clinical Manifestation of Calcium Deficiency
• Classical sign & symptoms of rickets
• Presentation may occur during infancy/childhood although
some cases are diagnosed at teen age
• Occur later than nutritional vitamin D deficiency
Calcium RDA Across Various Age-groups
Calcium RDA (mg/d)
Post menopausal women
1 – 3 yrs
4 – 6 yrs
7 – 9 yrs
10 – 12 yrs
16 -18 yrs
13 -15 yrs
* Nutrient Requirements & RDA in Indians. ICMR Report; National Institute & Nutrition, Hyderabad
Active absorbable algal calcium:
• Treated seaweed Cystophyllum fusiforme added HAI
(heated algal ingredient).
• Contains aminoacids which improve absorption at
intestinal villi and provide a neutral coat for +ve ionic
• Major feature: Vitamin D usually is not required for
the absorption of AAA cal
Benefits of AAA cal Women Health
Meets extra demands of Calcium especially in Pregnancy &
Absorption is independent of gastric acid content and
plasma vitamin D levels unlike CaCO3
Offers 57% better absorption than CaCO3.
Useful for Ca supplementation in elderly patients with Ca
deficiency & secondary Hyperparathyroidism due to its high
absorbability from the intestine.
Calcium is an important mineral with numerous health benefits with a
major role in bone development
Calcium deficiency has numerous implications in women from the fetal
phase to the elderly post-menopausal age
The major reason for calcium deficiency in pregnant women in poor
nutrition which can have detrimental effects on the bone health.
Calcium supplementation is thus imperative to ensure optimal bone as
well as extra-skeletal health in a woman throughout her life especially
during pregnancy & lactation.