Calcium Metabolism for Medical students, PG residents, Nursing students. Covers role of hormones, basics of osteoporosis.

1. Calcium Metabolism
Maj Mayank Jain
Base Hospital Delhi Cantt

2. Introduction
● Calcium, the most abundant mineral in the body, is found in some foods, added to
others, available as a dietary supplement, and present in some medicines (such as
antacids).
● 100 gm to 170 gm present in the body, out of which 99% is present in bones, 0.5%
in soft tissues, and 0.1% in ECF.
● Normal level in plasma is 9-11 mg/dl

3. Role in the body
● Vascular contraction
● Vasodilation
● Muscle function
● Nerve transmission
● Intracellular signaling
● Hormonal secretion
● Structural function

4. Daily requirement
Children (9 - 18 yr)
1300 mg/day
Adults
1000 mg/day
Pregnancy/lactation
1500 mg/day
Elderly
1200 mg/day
Children (upto 8yr)
800 mg/day

5. Rich in Calcium
Widely distributed in Milk,
Cheese, Egg yolk, Beans,
Lentils, Figs, Nuts, Cabbages

6. Absorption
● Calcium is taken in diet as phosphate,
carbonate and tartarate
● Only 40% of dietary Calcium is absorbed
from the gut
● Most absorption occurs in duodenum
and first half of jejunum
● It involves both active and passive
transport

7. Factors Which Increase
Absorption
● Vitamin D
● Parathyroid hormone
● Gastric acidity
● High protein diet
● Lysine and arginine
● Sugars and organic acids

8. Factors Which Decrease
Absorption
● Phytic acids (eg in cereals)
● Oxalates (eg green leafy veg)
● Excess Fibre in diet
● Malabsorption syndrome
● Glucocorticoids
● Excess phosphate,
magnesium, or iron in diet

9. Quick Question 1:1 is ideal. (Range - Not more than 2:1
and not less than 1:2)
What is the ideal Ca:P in diet for
optimum absorption of calcium ?

10. Another one
In Sprue Syndrome the absorption
of calcium suffers due to
formation of __________
Calcium Soap with Fatty Acids

11. Excretion
● Kidneys filter 250 mmol of Ca everyday
● 95% of it is reabsorbed in tubules
● This is finely modulated by PTH
● Serum ionised Ca is the principal regulator of PTH secretion by negative feedback
● Some calcium is excreted in gut as a constituent of bile and intestinal fluids

12. Parathyroid hormone
● Increases serum ionic Calcium
● Stimulate breakdown of bones and
release of Calcium.
● Activate vitamin D and increases GI
Calcium absorption
● Promotes Calcium reabsorption by
kidneys
● Inhibits proximal tubular reabsorption
of phosphate (thus increasing serum
ionic Calcium)

13. Calcitonin
● Decreases ionic Calcium in serum
● Inhibits osteoclast activity in bones
● Inhibits renal tubular reabsorption of
Calcium and phosphate
Thus, prevents Calcium loss from skeleton
during periods of Calcium mobilization from
body like pregnancy and lactation.

14. Hypercalcemia
When the serum calcium
level exceeds 11.0 mg/dl, it is
called as hypercalcaemia.

15. Hypercalcemia (causes)
1. Primary hyperparathyroidism: (Most common cause for OPD cases).
(a) Familial Hyperplasia-chief cells: Hyperplasia involving all four parathyroid glands
(15% cases)
(b) Tumours
● Solitary adenoma (80 to 85% cases)
● Multiple adenomas (2% cases)
● Parathyroid carcinoma (< 1% cases).

16. Hypercalcemia (causes)
(c) “Ectopic” hyperparathyroidism:
● Multiple endocrine neoplasia type I (MEN I) with pituitary and pancreatic
tumours.
● Multiple endocrine neoplasia type II (MEN II)
● Medullary carcinoma of thyroid
● Pheochromocytoma
2. Malignancy (Most important cause for hospital in-patients)
(a) Humoral factors
● PTH related protein (PTHγP)
● Growth factors, e.g. Tumor growth factor (TGF), Epidermal growth factor
(EGF), Platelet derived growth factor (PDGF).

17. Hypercalcemia (causes)
(b) Direct skeletal involvement by the tumours
● Direct erosion of bone by tumour
● Production of PGE2 by the tumour which can produce bone resorption.
(c) Haematological malignancies:
● Production of Cytokines: Interleukin-1, Tumor necrosis factor (TNF),
Lymphotoxin
● 1,25-di (OH)-D3 (Calcitriol) by lymphomas.
(d) Other Endocrine Causes:
● Hyperthyroidism, Hypothyroidism, Acromegaly, Acute adrenal
insufficiency.
(e) Granulomatous Diseases:
● Tuberculosis, sarcoidosis, berylliosis, coccidioidomycosis.

18. Hypercalcemia (causes)
(f) Overdosage of Vitamins:
● Vitamin A intoxication, and Hypervitaminosis D
(g) Drug-induced Hypercalcaemia (Iatrogenic):
● Thiazide diuretics, Spironolactone, Milk-alkali syndrome.
(h) Miscellaneous Other Causes
● Idiopathic hypercalcaemia of infancy (William syndrome)
● Familial hypocalcinuric hypercalcaemia
● Prolonged immobilisation
● Increased serum proteins
● Hyperalbuminaemia—due to haemoconcentration
● Hyperglobulinaemia—due to multiple myeloma
● Renal failure

19. Hypocalcemia
Hypocalcaemia is said to exist
when serum calcium is less than
8.5 mg/dl as determined by a
standard method.

20. Hypocalcemia (causes)
(a) Reduction in serum albumin: (Hypoalbuminaemia)
● Malnutrition, malabsorption states
● Nephrotic syndrome
● Chronic liver disease and liver failure
● Protein losing enteropathy.
(b) Hypoparathyroidism
● May be surgical-induced partial or complete (90% cases)
● Idiopathic—may be autoimmune (10% cases)
● Bio-inactive parathyroid hormone (PTH)
● Transient hypoparathyroidism of infancy, may be partial.

21. Hypocalcemia (causes)
(c) Renal Diseases and Renal Failure
● Renal tubular dysfunction
● Acute tubular necrosis
● Chronic renal failure (contributing factors for low calcium values are):
1. Hyperphosphataemia
2. Impaired synthesis of 1,25-diOH D3 (calcitriol) due to inadequate renal mass due to
disease process and tubular damage.
(d) Pseudohypoparathyroidism
(e) Hypoparathyroidism (in association with other diseases)
● Addison’s disease
● Pernicious anaemia
● Fungal disease like candidiasis

22. Hypocalcemia (causes)
(f) Other Miscellaneous Causes
● Acute pancreatitis: Haemorrhagic or oedematous
● Osteomalacia and rickets due to vitamin D deficiency or resistance.
● Medullary carcinoma of thyroid
● Hungry bone syndrome
Magnesium deficiency
(g) Iatrogenic:
● Foscarnate
● Mithramycin, glucocorticoids, calcitonin
(h) Neonatal hypocalcaemia
● Prematurity
● Poor feeding

23. Vitamin D Metabolism
(A molecule of D3)

24. Basics
● Vitamin D is a fat-soluble vitamin that is naturally present in very few foods.
● Vitamin D obtained from sun exposure, food, and supplements is biologically
inert and must undergo two hydroxylations in the body for activation.
● The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D
[25(OH)D], also known as calcidiol
● The second occurs primarily in the kidney and forms the physiologically active
1,25-dihydroxyvitamin D [1,25(OH)2
D], also known as calcitriol

25. Role in the body
● Promotes calcium absorption
● Bone growth and remodelling
● Modulation of cell growth
● Neuromuscular function
● Immune function
● Reduces inflammation
● Regulates ~ 2000 genes

27. Action of
Calcitriol
(Net increase of Ca and P in ECF)
● Promotes absorption of Calcium
and phosphorus from intestine
● Increases re absorption of
phosphate in the kidney
● Acts on bone to release Calcium
and phosphate

28. Recommended intake
Infants 400 IU (10mcg)
Adults 600 IU (15mcg)
>70 Years 800 IU (20mcg)
(Countries like USA and Canada follow
routine fortification of the milk supply
with Vit D)

29. How much Sun ?
Most people meet a large portion of Vit
D requirement through sun exposure.
5–30 minutes of sun exposure between
10 AM and 3 PM at least twice a week to
the face, arms, legs, or back without
sunscreen usually lead to sufficient
vitamin D synthesis.
UVB does not penetrate glass, thus
sunlight through a window does not
produce Vit D.

30. Deficiency
Serum concentration of 25(OH)D is
the best indicator of vitamin D
status (Half life of 15 days)
Levels <12 ng/ml are related to
rickets in children and osteomalacia
in adults
30-50 ng/ml is considered optimum
for skeletal metabolism

31. Risk Factors
● Exclusive Breastfeeding
● Elderly
● Obese individuals
● IBD and Malabsorption Syndromes
● Dark skinned races
● Drug intake :
○ Corticosteroids
○ Cholestyramine
○ Orlistat
○ Phenobarbital
○ Phenytoin

32. Bowing of Long Bones Swelling of wrists and ankles
Features of Rickets

33. What are these signs called ?
Harrison’s Groove
Rachitic Rosary
Craniotabes

34. Radiological findings
Cupping and fraying of metaphyses Fraying of metaphyses

35. Bone Density
scans
Bone density scan uses
low energy X rays for
early detection of
mineral loss and bone
thinning.
Recommended for post
menopausal women
and adults above 50 yr
age.

36. Hypervitaminosis
Levels >60 ng/ml are related to various
adverse effects
● Loss of apetite
● Nausea, vomiting
● Excess thirst and urination
● Muscular weakness
● Calcium deposits in soft tissues
● Renal Calculi
● Cardiovascular diseases

37. To D or not to D ?*
*(Excerpts from MJAFI Editorial of October 2015)
“India is a country of widespread Calcium and Vit D Deficiency”
“The scare generated regarding adverse impact of this supplementation is mainly from
studies with weak evidence and generated from populations which are largely Calcium
and Vit D sufficient”
“These studies were conducted in countries where daily calcium intake is to the tune of
800-1200mg. Countries with intake as low as 300-500mg daily have excess
cardiovascular mortality by itself due to this reason.”

38. Osteoporosis
● Decrease In Bone Mass
● Disrupted Bone Microarchitecture
Causes
● Increased Age
● Menopause
● Metabolic Abnormalities
Abnormally low bone mass and defects in bone
microstructure

39. Osteoporosis : Diagnosis
● DEXA Scan
○ Osteopenia = T-score 1 to
2.5 standard deviations
below the peak bone mass
of a 25 year old individual
○ Osteoporosis = T-score
>2.5 standard of
deviations below the peak
bone mass of a 25 year old
individual

40. Osteoporosis : Diagnosis
● pQCT
○ Bone mineral density (BMD)
○ Marrow and cortical
Cross-Sectional Area (CSA)
○ Cortical Thickness (CoTh)
○ Periosteal and endosteal
circumference
○ Cross-Sectional Moment of Inertia
(CSMI)
○ Polar moment of inertia
○ Strength Strain Index (SSI)