Calcium & Bone

Question 1

Parathyroid glands and calcium

Answer 1

sense low serum calcium and increase PTH secretion

Question 2

releases calcium and phosphorus

Answer 2

bone ultimately –> increases serum calcium

Question 3

kidney and calcium

Answer 3

• increases calcitriol formation

- decreases excretion of calcium

Question 4

small intestine

Answer 4

increases absorption of dietary calcium –> increases serum calcium

Question 5

what induces parathyroid hormone release

Answer 5

hypocalcemia

Question 6

parathyroid hormone

Answer 6

↑ 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)

Question 7

teriparatide

Answer 7

Recombinant PTH: FDA approved for osteoporosis (given subcutaneously)

Question 8

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

Answer 8

25 hydroxyvitamin D3, calcifediol in the liver.

Question 9

25 hydroxyvitamin D3, calcifediol in the liver…

Answer 9

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.

Question 10

Effect of Calcitonin release and what triggers this?

Answer 10

calcitonin released in response to hypercalcemia, decreases bone resorption.

Question 11

Vit D activation

Answer 11

➢ 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

Question 12

Dihydroxyvitamin D3

Answer 12

increases the intestinal absorption of calcium.

Question 13

Recombinant PTH: FDA approved for osteoporosis

Answer 13

teriparatide

Question 14

Actions of Vitamin D

Answer 14

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

Question 15

Uses of Vit D

Answer 15

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

Question 16

Calcitonin

Answer 16

➢ 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

Question 17

Uses of Calcitonin

Answer 17

• Hypercalcemic states- Paget’s disease

* Post menopausal osteoporosis

Question 18

Actions of Calcitonin

Answer 18

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

Question 19

Net effect of PTH

Answer 19

↓ Plasma PO4

↑ Plasma Ca

Question 20

Net Effect of Vit D

Answer 20

↑ Plasma Ca

↑ Plasma PO4

Question 21

Net Effect of Calcitonin

Answer 21

↓ Plasma PO4

↓ Plasma Ca

Question 22

PTH’s effect on Intestine

Answer 22

↑ Ca and ↑ PO4 absorption

Question 23

PTH’s effect on kidney

Answer 23

↓Ca and ↑ P04 excretion

Question 24

PTH’s effect on bone

Answer 24

↑ bone resorption (High dose, increasing osteoclasts)

↑ bone formation (Low dose by increasing osteoblasts)

Question 25

Vit D's effect on Intestine

Answer 25

↑ Ca and P04 absorption

Question 26

Vit D's effect on Kidney

Answer 26

↓Ca and PO4 excretion

Question 27

Vit D's effect on Bone

Answer 27

↑ bone resorption | ↑ bone formation

Question 28

Calcitonin's effect on intestine

Answer 28

NONE

Question 29

Calcitonin's effect on kidney

Answer 29

↑ Ca and PO4 excretion

Question 30

Calcitonin's effect on bone

Answer 30

↓ bone resorption

Question 31

Estrogens effect on Calcium and bone

Answer 31

* Inhibition of PTH stimulated bone resorption | * Use in postmenopausal osteoporosis

Question 32

Glucocorticoids effect on Calcium and bone

Answer 32

➢ 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

Question 33

Bisphosphonates MOA

Answer 33

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

Question 34

Bisphosphonates

Answer 34

➢ Etidronate , Alendronate | ➢ Pamidronate, Residronate, Zolendronate

Question 35

Bisphosphonates Uses

Answer 35

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

Question 36

Bisphosphonates A/E

Answer 36

* 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

Question 37

Plicamycin (Mitramycin)

Answer 37

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

Question 38

Thiazide diuretics

Answer 38

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

Question 39

Causes of Hypercalcemia

Answer 39

* Hyperparathyroidism * Malignancy * Hypervitaminosis * Sarcoidosis

Question 40

Hypercalcemia Treatment

Answer 40

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

Question 41

Causes of Hypocalcemia

Answer 41

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

Question 42

Treatment for Hypocalcemia

Answer 42

``` 1. Calcium ➢ IV: • Calcium chloride • Calcium gluconate* • Calcium gluceptate ➢ Oral: • Calcium lactate • Calcium carbonate • Calcium citrate ``` 2. Vitamin D: Calcitriol

Question 43

Osteoporosis: • Def • Causes

Answer 43

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

Question 44

Treatment for Osteoporosis

Answer 44

* Hormone Replacement Therapy = Estrogen + progesterone * SERMs = Raloxifene * Teriparatide * Bisphoshonates = Alendronate, residronate * Other treatment options: * Calcitonin, Vitamin D, Calcium

Question 45

Paget's Disease of Bone • def • diagnosis

Answer 45

➢ 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

Question 46

Treatment for Paget's Disease of Bone

Answer 46

* Calcitonin * Bisphosphonates: * Etidronate * alendronate * residronate

Question 47

calcipotriene

Answer 47

Topical VitD: used for treatment of psoriasis