Calcium, Vitamin D,osteoporosis by Dr. Saritha Manem

2. Calcium
• Calcium is 5 th most common element of our
body after C,O,H,N, making 2 % of our body
weight- 1-1.5kg in an adult.
• More than 99% stored in bones & teeth.
• Rest distributed to plasma & all tissues of
cells.
• Normal levels = 9 to 11mg/dL

5. Calcium
Ionized Protein
Bound
Complexed
to anions
50 %
exerts the
biological
action
40 % to
albumin
10 %
phosphates,
citrates

7.  Calcium is absorbed from entire intestine by carrier
mediated active transport under influence of Vit –
D.
 Phytates ,phosphates oxalates &tetracyclines
complex calcium in insoluble form - interfere with
absorption.
 Vit –D increases and calcitonin decreases proximal
tubular reabsorption & PTH increases distal tubular
reabsorption.
 Daily dietery allowance for calcium- 0.8-1.5 g per
day.

8. Regulation of plasma level of calcium

10. Preparations of calcium
S.N
o
Preparation Characteristic
1 Calcium chloride 27 % calcium , highly irritant ,
not for IM use. Orally also
irritable
2 Calcium gluconate 9 % calcium , non irritating
Sense of warmth produced on
injection
3 Calcium lactate 13 % calcium, orally well
tolerated , non irritating
4 Calcium dibasic
phosphate
23 % calcium , used as
antacid and calcium
supplement
5 Calcium carbonate 40 % calcium , tasteless, non
irritating , used as antacid

11. Hypocalcemia
• ↑neuromuscular
irritability
• Hyperactive reflexes
• Paresthesia, tetany,
seizures
• Laryngeal spasm
• Teeth hypoplasia
• Bone fractures
• Skin & nails atrophy

12. Uses of calcium
• Tetany (Hypocalcemia) :
• 10 -20 ml of calcium gluconate (90 –180mg)
injected IV over 10 min, followed by slow IV
infusion.
• Total of 50-100 ml of 10 % calcium gluconate
required to reverse the muscle spasms over 6
hrs.
• Long term oral treatment to provide. 1- 1.5 g of
calcium daily is instituted along with Vit D.

13. • As dietary supplement:
• Children 1-10 yr :0.8 – 1.2 g /day
• Young adult, pregnant, lactating female: 1.2 -1.5 g
• Men , women 25 -50 yrs : 1 g
• Women> 50 yr not taking HRT: 1.5 g
• Osteoporosis – with
HRT/Raloxifene/alendronate
• Placebo
• As antacid
• Cardiac arrest
Other uses of calcium

14. Hypercalcemia
• Lethargy, anorexia, weakness
• Nausea, vomiting, constipation
• Polyuria, dehydration
• Irregularities in heart
• Metastatic calcification
• Mental changes indicate severe
hypercalcemia

15. • Polypeptide – 84 AA(1-34 biological action)
• Mol. Wt = 9500
•Released by chief cells in the parathyroid
gland.
•Chief cells contain receptors for Ca2+
• Calcium-sensing receptor (CaSR)
•↓ in plasma Ca2+
levels mediates the
release of PTH by ↑ Camp and rise inhibits
secretion.
•PTH rapidly degraded in kidney & liver.
Parathyroid Hormone (PTH)

16. Actions of PTH-
Increases plasma Ca+2 levels
Increases resorption
of calcium from bone
Increases resorption
of calcium from bone
Increases
number of
bone
remodelling
units
Increases
number of
bone
remodelling
units
Activates the
osteoclasts
Activates the
osteoclastsIncreases
calcium
reabsorption
in distal
tubule
Increases
calcium
reabsorption
in distal
tubule
No direct effect . Increases calcium
absorption by enhancing formation
of calcitriol in kidney by activating
1α hydroxylase..calcitriol
promotes ca+2 absorption.
No direct effect . Increases calcium
absorption by enhancing formation
of calcitriol in kidney by activating
1α hydroxylase..calcitriol
promotes ca+2 absorption.

17. 
Cinacalcet- It activates ca+2 sensing receptor
(CaR) I parathyroid and blocks PTH secretion
.Indicated in secondary hyperparathyroidism and
parathyroid tumour.

Teriperatide- Recently approved recombinant
preperation for treatment of severe
osteoporosis.It stimulates new bone formation.

18. • A hypocalcemic hormone discovered by
Copp .
• 32 AA , 3600 Mol.Wt .
• Produced by para follicular- C-cells of
thyroid gland.
• Physiological effects are opposite to those
of PTH.
• Rapid acting, short term regulator of
plasma Ca levels.
Calcitonin

19. Calcitoni
n
Bone Kidney
Directly inhibits
the osteoclasts of
bone
Decreased
bone
resorption
↓↓ plasma calcium
↓↓ Plasma
phosphate
Inhibits the
reabsorption of Ca &
Po4 in proximal
renal tubule
Actions of calcitonin

20. Preparations of calcitonin
• Porcine (Natural) calcitonin:
• Antigenic
• Synthetic salmon calcitonin:
• More potent due to slower metabolism
• Synthetic human calcitonin:
• 1 IU = 4 μg of std preparation
• Calcitonin is given by SC/IM routes. Salmon
calcitonin is also available as nasal spray

21. Uses of calcitonin
• Hypercalcemia states (e.g associated with
neoplasia) :hyperthyroidism,hyper vitaminosis
D,hyper calcemia of malignancy.
• Pagets disease of bone:
• Chronic use of calcitonin relieves pain &
reduces some neurological complications , but
biphosphonates T/t of choice.
• Postmenopausal osteoporosis &
corticosteroid induced osteoporosis:
• Salmon calcitonin is used as nasal spray along
with Vit D supplements 200 IU /day

22. Vitamin D
• Vitamin D: collective name given to
antirachitic substances synthesized in body
& found in foods activated by UV radiation
• D2: calciferol- present in irradiated food-
yeasts, fungi, bread, milk
• D3: cholecalciferol- synthesized in skin
under influence of UV rays.

23. Activation of Vit D
7
dehydrocholester
ol
Ergosterol
Cholecalciferol Vit
D3
Calciferol Vit D2
Calcifediol (25 OH
Vit D3)
Calcitriol (1,25 (OH)2
Vit D3)
25 OH Vit D2
1,25 (OH)2 Vit D2
UV Light
Liver
microsomes
Kidney mitochondria
Active forms

25. Actions of Vit D
• Enhances absorption of calcium & phosphate from
intestine
• Enhances resorption of calcium & phosphate from
bone , similar mechanism to PTH.
• Calcitriol enhances the tubular resorption of
calcium and phosphate in kidneys.
• Cell differentiation: Particularly of collagen & skin
epithelium.
• Immunity: Important for Cell Mediated Immunity &
coordination of the immune response.

26. Pharmacokinetics
• Well absorbed from intestines in presence of bile
salts
• Absorption of D3 little better than D2
• In circulation bound to alpha globulin and stored
mainly in adipose tissues for months.
• Hyroxylated in liver to active & inactive
compounds
• Half life varies 1- 18 days , 25-OH D3 has longest
half life
Unitage
• 1 μg of cholecalciferol = 40 IU of Vit D
• RDA = 400 IU /day

27. Preparations
• Ergocalciferol:Vit D2
• oral capsules
• Cholecalciferol: Vit D3
• Oral/IM injection 3-6 lac IU every 2-6 month
interval .
• Calcitriol:
• oral capsules & solution 0.25 - 1 μg daily or IV
on alternate days .
• Alfacalcidiol & dihydrotachysterol:
• Prodrugs orally effective and rapidly
biotransformed into calcitriol in liver. They are
effective in renal bone disease,vit D resistant
and dependent rickets & hypoparathyroidism.
• Calcipotriol : Vitamin D analog used topically in

28. Uses of Vit D
1. Prophylaxis: 400 IU/day and treatment of rickets
& osteomalacia - 3000 -4000 IU/day or
alternatively Oral/IM injection 3-6 lac IU every
2-6 month interval .
2. Metabolic rickets :
1. Vit D resistant rickets: high doses.
2. Vit D dependent rickets: calcitriol or
alphacalcidiol
3. Renal rickets: calcitriol or alphacalcidiol .
3. Senile or post menopausal osteoporosis
4. Hypoparathyroidism : calcitriol or alphacalcidiol
are better
5. Fanconis syndrome: Vit D can raise lowered
phosphate levels that occur in this condition.

29. Bisphosphonates(BPNs)
• Analogs of pyrophosphate
• Most effective anti resorptivedrugs.
• 3 generaions according to potency
• First generation:
• Etidronate
• Second generation:
• Pamidronate
• Alendronate
2nd
and 3rd
generations more potent,highly
efficacious with additional modes of action.
• Third generation :
• Risedronate
• Zoledronate

30. 
Have stronger affinity for calcium phosphate.

Have selective action on calcified tissues.

2 main components of bone are protein
matrix and solid mineral phase
(hydroxyapatite)

31. • Mechanism of action
Protect
dissolution of
hydroxyapatite
from bone
 Accelerates
apoptosis of
osteoclasts
 Inhibits release
of IL-6 to supress
differentiation of
osteoclast
precursors.

32. Bisphosphonates uses and adverse
effects• Uses
• Pagets disease of bone: Treatment of choice
• For prevention and treatment of post-
menopausal osteoporosis .
• To prevent corticosteroid induced osteoporosis
along with calcium carbonate .
• Hypercalcemia of malignancy : Zolendronate
• Control hypercalcemia of hyperparathyroidism.
• To relieve pain of lytic bone lesions.
• Nausea, vomiting diarrhoea, esophagitis, peptic
ulcer, fever, myalgia, hypocalcemia, headache &
skin rashes
• osteonecrosis , renal impairment .
• Adverse effects

34. Actions of Vit D
Groff & Gropper, 2000
• 1,25-(OH)2 D
binds to
vitamin D
receptor (VDR)
in nucleus
• ↑ in calbindin
(Ca-binding
protein)
• Net effect is ↑
absorption of
calcium &
phosphorus
from intestine

35. • Highly polar so less poorly absorbed through
GIT
• Part of absorbed drug is incorporated into
bone & remains for long periods years to
months
• The free drug is excreted unchanged in urine
• Pharmacokinetics (BP)

36. Treatment of hypercalcemia
• Hydration & dietary calcium restriction < 400
mg/day
• Sodium chloride:
• Saline administration will cause renal
elimination of calcium
• Furosemide : 20 -40 mg every 2-4 hrs
• Glucocorticoids: reduce intestinal absorption &
tubular reabsorption of calcium
• Calcitonin: 4 IU/kg SC OR IM twice or once daily can
be increased to 8 IU/kg IM 6 hrly
• Mithramycin : 25 μg/kg IV over period of 4- 6 Hrs
• Inorganic phosphate: phosphosoda 5 ml TDS