Calcium & Bone Flashcards
Parathyroid glands and calcium
sense low serum calcium and increase PTH secretion
releases calcium and phosphorus
bone ultimately –> increases serum calcium
kidney and calcium
- increases calcitriol formation
- decreases excretion of calcium
small intestine
increases absorption of dietary calcium –> increases serum calcium
what induces parathyroid hormone release
hypocalcemia
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)
teriparatide
Recombinant PTH: FDA approved for osteoporosis (given subcutaneously)
Vitamin D3 from the diet or from exposure to sunlight is hydroxylated to
25 hydroxyvitamin D3, calcifediol in the liver.
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.
Effect of Calcitonin release and what triggers this?
calcitonin released in response to hypercalcemia, decreases bone resorption.
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
Dihydroxyvitamin D3
increases the intestinal absorption of calcium.
Recombinant PTH: FDA approved for osteoporosis
teriparatide
Actions of Vitamin D
- ↑Absorption of Ca and Phosphate from intestine
- ↑ tubular reabsorption of calcium
- Help bone mineralization
Uses of Vit D
- Hypocalcemia caused by diseases -
- Nutritional rickets, hypoparathyroidism, renal disease, osteoprosis, amlabsorption
- Topical calcipotriene – used for treatment of psoriasis
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
Uses of Calcitonin
- Hypercalcemic states- Paget’s disease
* Post menopausal osteoporosis
Actions of Calcitonin
- Inhibits osteoclastic bone resorption
- Inhibits calcium and phosphate reabsorption in kidney
- ↓ serum calcium and phosphate
Net effect of PTH
↓ Plasma PO4
↑ Plasma Ca
Net Effect of Vit D
↑ Plasma Ca
↑ Plasma PO4
Net Effect of Calcitonin
↓ Plasma PO4
↓ Plasma Ca
PTH’s effect on Intestine
↑ Ca and ↑ PO4 absorption
PTH’s effect on kidney
↓Ca and ↑ P04 excretion
PTH’s effect on bone
↑ bone resorption (High dose, increasing osteoclasts)
↑ bone formation (Low dose by increasing osteoblasts)
Vit D’s effect on Intestine
↑ Ca and P04 absorption
Vit D’s effect on Kidney
↓Ca and PO4 excretion
Vit D’s effect on Bone
↑ bone resorption
↑ bone formation
Calcitonin’s effect on intestine
NONE
Calcitonin’s effect on kidney
↑ Ca and PO4 excretion
Calcitonin’s effect on bone
↓ bone resorption
Estrogens effect on Calcium and bone
- Inhibition of PTH stimulated bone resorption
* Use in postmenopausal osteoporosis
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
Bisphosphonates MOA
- Retard the formation and dissolution of hydroxyapatite crystals in bone
- Inhibit osteoclast mediated bone resorption
Bisphosphonates
➢ Etidronate , Alendronate
➢ Pamidronate, Residronate, Zolendronate
Bisphosphonates Uses
- Postmenopausal Osteoporosis
- Hypercalcemia associated with malignancy
- Paget’s disease
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
Plicamycin (Mitramycin)
Cytotoxic antibiotic • Reduce serum calcium levels and bone resorption ➢ Use : • Pagets disease • Hypercalcemia
Thiazide diuretics
➢ Increased calcium reabsorption from renal tubules (acts at DCT)
➢ Use: Idiopathic hypercalciuria
Causes of Hypercalcemia
- Hyperparathyroidism
- Malignancy
- Hypervitaminosis
- Sarcoidosis
Hypercalcemia Treatment
- Rehydration with saline and diuresis with furosemide
- Pamidronate/zoledronate - hypercalcemia in malignancy
- Calcitonin
- Plicamycin
- Glucocorticoids - hypercalcemia in sarcoidosis
Causes of Hypocalcemia
- Hypoparathyroidism
- Vitamin D defeciency
- Chronic kidney disease
- Malabsorption
Treatment for Hypocalcemia
1. Calcium ➢ IV: • Calcium chloride • Calcium gluconate* • Calcium gluceptate ➢ Oral: • Calcium lactate • Calcium carbonate • Calcium citrate
- Vitamin D: Calcitriol
Osteoporosis:
• Def
• Causes
➢ Abnormal loss of bone predisposing to fractures
➢ Causes
• Postmenopausal
• Long term use of glucocorticoids, heparin, thiazides, phenytoin
• Thyrotoxicosis
• Hyperparathyroidism
Treatment for Osteoporosis
- Hormone Replacement Therapy = Estrogen + progesterone
- SERMs = Raloxifene
- Teriparatide
- Bisphoshonates = Alendronate, residronate
- Other treatment options:
- Calcitonin, Vitamin D, Calcium
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
Treatment for Paget’s Disease of Bone
- Calcitonin
- Bisphosphonates:
* Etidronate
* alendronate
* residronate
calcipotriene
Topical VitD: used for treatment of psoriasis
