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Flashcards in Calcium & Bone Deck (47):
1

Parathyroid glands and calcium

sense low serum calcium and increase PTH secretion

2

releases calcium and phosphorus

bone ultimately --> increases serum calcium

3

kidney and calcium

- increases calcitriol formation
- decreases excretion of calcium

4

small intestine

increases absorption of dietary calcium --> increases serum calcium

5

what induces parathyroid hormone release

hypocalcemia

6

parathyroid hormone

↑ serum Ca by increasing:
a. Formation of active 1,25 dihydroxyvitamin D3 in the kidney, which increases the absorption of calcium in the gut
b. Bone resorption of calcium
c. Kidney reabsorption of calcium (and increasing phosphate excretion)

7

teriparatide

Recombinant PTH: FDA approved for osteoporosis (given subcutaneously)

8

Vitamin D3 from the diet or from exposure to sunlight is hydroxylated to

25 hydroxyvitamin D3, calcifediol in the liver.

9

25 hydroxyvitamin D3, calcifediol in the liver...

a. This intermediate (hydrolyzed VD3 from diet or from sunlight exposure) is further hydroxylated in the kidney to 1,25 dihydroxyvitamin D3, calcitriol (Rocaltrol).
b. Dihydroxyvitamin D3 increases the intestinal absorption of calcium.

10

Effect of Calcitonin release and what triggers this?

calcitonin released in response to hypercalcemia, decreases bone resorption.

11

Vit D activation

➢ 7-Dehydrocholesterol
(Skin) ⇓ UV light
➢ Cholecalciferol(D3)
⇓ Liver
➢ Calcifediol 25(OH)D3
⇓ kidney
➢ *Calcitriol 1,25(OH)2D3

Calcitriol 1,25(OH)2D3 = Most active metabolite of vitamin D

12

Dihydroxyvitamin D3

increases the intestinal absorption of calcium.

13

Recombinant PTH: FDA approved for osteoporosis

teriparatide

14

Actions of Vitamin D

• ↑Absorption of Ca and Phosphate from intestine
• ↑ tubular reabsorption of calcium
• Help bone mineralization

15

Uses of Vit D

• Hypocalcemia caused by diseases -
• Nutritional rickets, hypoparathyroidism, renal disease, osteoprosis, amlabsorption
• Topical calcipotriene – used for treatment of psoriasis

16

Calcitonin

➢ Secreted by Parafollicular ‘C’ cells of thyroid
• Released in response to hypercalcemia and ↓ bone resorption

➢ Salmon calcitonin - i.m/s.c, nasal spray

➢ Actions
• Inhibits osteoclastic bone resorption
• Inhibits calcium and phosphate reabsorption in kidney
• ↓ serum calcium and phosphate

➢ Uses:
• Hypercalcemic states- Paget’s disease
• Post menopausal osteoporosis

17

Uses of Calcitonin

• Hypercalcemic states- Paget’s disease
• Post menopausal osteoporosis

18

Actions of Calcitonin

• Inhibits osteoclastic bone resorption
• Inhibits calcium and phosphate reabsorption in kidney
• ↓ serum calcium and phosphate

19

Net effect of PTH

↓ Plasma PO4
↑ Plasma Ca

20

Net Effect of Vit D

↑ Plasma Ca
↑ Plasma PO4

21

Net Effect of Calcitonin

↓ Plasma PO4
↓ Plasma Ca

22

PTH's effect on Intestine

↑ Ca and ↑ PO4 absorption

23

PTH's effect on kidney

↓Ca and ↑ P04 excretion

24

PTH's effect on bone

↑ bone resorption (High dose, increasing osteoclasts)
↑ bone formation (Low dose by increasing osteoblasts)

25

Vit D's effect on Intestine

↑ Ca and P04 absorption

26

Vit D's effect on Kidney

↓Ca and PO4 excretion

27

Vit D's effect on Bone

↑ bone resorption
↑ bone formation

28

Calcitonin's effect on intestine

NONE

29

Calcitonin's effect on kidney

↑ Ca and PO4 excretion

30

Calcitonin's effect on bone

↓ bone resorption

31

Estrogens effect on Calcium and bone

• Inhibition of PTH stimulated bone resorption
• Use in postmenopausal osteoporosis

32

Glucocorticoids effect on Calcium and bone

➢ Antagonize the vitamin D stimulated intestinal calcium absorption
➢ Stimulate renal calcium excretion
➢ Prolonged administration- can cause osteoporosis in adults and stunted growth in children

• Use: reversing hypercalcemia in lymphomas, sarcoidosis

33

Bisphosphonates MOA

• Retard the formation and dissolution of hydroxyapatite crystals in bone
• Inhibit osteoclast mediated bone resorption

34

Bisphosphonates

➢ Etidronate , Alendronate
➢ Pamidronate, Residronate, Zolendronate

35

Bisphosphonates Uses

• Postmenopausal Osteoporosis
• Hypercalcemia associated with malignancy
• Paget’s disease

36

Bisphosphonates A/E

• Gastric irritation (Except etidronate)
• Tell patient to take drug with pleanty of water and sit in an upright position for 20-30 minutes following drug (bc causes reflux esophagitis)
• Esophageal ulceration

37

Plicamycin (Mitramycin)

Cytotoxic antibiotic
• Reduce serum calcium levels and bone resorption
➢ Use :
• Pagets disease
• Hypercalcemia

38

Thiazide diuretics

➢ Increased calcium reabsorption from renal tubules (acts at DCT)
➢ Use: Idiopathic hypercalciuria

39

Causes of Hypercalcemia

• Hyperparathyroidism
• Malignancy
• Hypervitaminosis
• Sarcoidosis

40

Hypercalcemia Treatment

• Rehydration with saline and diuresis with furosemide
• Pamidronate/zoledronate - hypercalcemia in malignancy
• Calcitonin
• Plicamycin
• Glucocorticoids - hypercalcemia in sarcoidosis

41

Causes of Hypocalcemia

• Hypoparathyroidism
• Vitamin D defeciency
• Chronic kidney disease
• Malabsorption

42

Treatment for Hypocalcemia

1. Calcium
➢ IV:
• Calcium chloride
• Calcium gluconate*
• Calcium gluceptate
➢ Oral:
• Calcium lactate
• Calcium carbonate
• Calcium citrate

2. Vitamin D: Calcitriol

43

Osteoporosis:
• Def
• Causes

➢ Abnormal loss of bone predisposing to fractures
➢ Causes
• Postmenopausal
• Long term use of glucocorticoids, heparin, thiazides, phenytoin
• Thyrotoxicosis
• Hyperparathyroidism

44

Treatment for Osteoporosis

• Hormone Replacement Therapy = Estrogen + progesterone

• SERMs = Raloxifene

• Teriparatide

• Bisphoshonates = Alendronate, residronate

• Other treatment options:
• Calcitonin, Vitamin D, Calcium

45

Paget's Disease of Bone
• def
• diagnosis

➢ Localized bone disease characterized by uncontrolled bone resorption with secondary new bone formation

➢ Diagnosis:
• Elevated serum alkaline phosphatase
• Urinary hydroxyproline levels
• abnormal bones on Xray

46

Treatment for Paget's Disease of Bone

• Calcitonin
• Bisphosphonates:
• Etidronate
• alendronate
• residronate

47

calcipotriene

Topical VitD: used for treatment of psoriasis