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29 Cards in this Set

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Bone Metabolic Unit
1. Crack
2. Osteoclast
3. Osteoblast
4. Mineralization
Normal Bone Turnover
1. Bone formation
2. Bone trunover
Endogenous Ca/PO4 secondary regulators

net effect:
Major:
1. PTH
2. Vitamin D

Minor:
1. calcitonin
2. Estrogen
3. Glucocorticoids

Lower Ca+2/PO4-3 in serum
major and minor regulators
Exogenous Ca/PO4 secondary regulators

net effect:

Uses:
1. Bisphosphates
2. SERM (Selective Estrogen Receptor Modulator)
3. Intermitent PTH (parathyroid hormone)

Lower Ca+2/PO4-3 in serum

Pagets Disease
Hypercalcemia
Osteoporosis
effects of Estrogen on bone metabolism

use:
1. reduces PTH-induced bone resorption
2. prevents accelerated bone loss during period immediate post-menopausal
3. transciently increases bone mass in postmenopausal women
4. may have effect on bone remodeling because estrogen receptors are found in bone

used to prevent post-menopausal osteoporosis
Natural Estrogens
1. Estradiol
2. Estradone
3. Estriol
4. Conjugated estrogens
Synthetic estrogens
1. Ethynil estradiol
2. Mestranol
3. Diethylstilbestrol
Characteristics of postmenopausal osteoporosis
1. slower bone turnover
2. fractures take longer to repair
3. osteomalasia (lack of bone mineralization) prevents last step to form strong bones
Effects of Glucocorticoids on bone metabolism

Net effect

uses
1. antagonize vitamin D-stimulated calcium transport
2. ↑ calcium (Ca+2) excretion by kidney
3. ↑PTH-stimulated bone resoptions
4. slow bone turnover
5. prevent mineralization

Lower calcium (Ca+2) in serum

used in vitamin D intoxication
tumors that secrete 1,25(OH)2 D3, annd hypercalcemia
6 Analogs of Glucocorticoids
1. cortisol
2. prednisone
3. dexamethasone
4. tri-amcinnolone
5. beclomethasone
6. triamcinolone acetonide

Lower calcium (Ca+2) in serum

used in vitamin D intoxication
tumors that secrete 1,25(OH)2 D3, annd hypercalcemia
Adverse effects of chronic exposure to glucocorticoids
1. osteoporosis in adults
2. stunted skeletal growth in children
Effects of Bisphonates on bone metabolism

Net effect

uses
1. B. are taken up by bone and integrated in bone matrix
2. help form new osteoblast
3. retard bone formation/dissolution of CaPO4 (hydroxyapatite) crystals within and outside skeletal system
4. assist rebuild bone
5. ~50% drug absorved accumulates in bone

net effect: increase bone density

used to slow progression of postmenopausal osteoporosis,
reduces fractures, treat pagets disease
5 Analogs of Bisponates

Net effect:

uses:

Adverse effects:
1. Elen-dronate
2. Eti-dronate
3. Pami-dronate
4. Rise-dronate
5. Tilu-dronate

net effect: increase bone density

used to slow progression of postmenopausal osteoporosis,
reduces fractures, treat pagets disease

adverse effects: esophageal ulceration
characteristics of SERM drugs
Selective Estrogen Receptor Modulator

net effect: decrease bone loss

are mixed estrogen agonists (can act as agonist, partial agonists, and antagonists depending on tissue type), but do not decrease the risk of breast and endometrial cancer

antagonist effect in breast tissue
Effects of SERM on bone metabolism

net effect:

uses:

adverse effects:
decrease bone loss

prevents osteoporosis in post-menopausal women

adverse effectt: increase Venous thrombosis risk
SERM used in regulation of Bone metabolism
1. Ralo-xifen
2. Tamo-xifen
effect of PTH on Bone metabolism when given at intermitent doses
1. ↑ Ca reabsorption @ kidney
2. ↑ osteoclast activity
3. ↑ vitamin D production
4. ↓ Phosphate reabsorption

-net effect is to ↑ calcium in serum
-increase bone formation without affecting bone resorption
-Ca regulates PTH secretion
PTH analog used in regulating bone metabolism:

Adverse effect/caution:
Terri-paratide (peptide segment of PTH)

Adverse effect: Osteo-sarcoma (bone tumor)
Calcium metabolism
1. Ca is absorbed by the Intestine
2. Ca is re-absorbed (Excreted) by Kidney
3. low Ca conc. in serum induce PTH release
4. stored in bone (mineralization)
5. released from bone (demineralization)
Consequences of abnormal Calcium metabolism
1. Hypo-calcemia
2. Hyper-calcemia
Symptoms associated with Hypo-calcemia
-tetany
-para-esthesias
-muscle cramps
-osteoporosis
-convulsions
-decrease hematopoietic capacity
Symptoms associated with Hyper-calcemia
-muscle weakness
-CNS depression, coma
-Calcium nephrolithiasis
Effects of Vitamin D on Ca and PO4 metabolism

Net effect:
1. @ intestine: ↑Ca ↑PO4 absorption
2. @ kidney: ↓Ca ↓PO4 excretion
3. @ bone:
↑Ca ↑PO4 resorption by 1,25-(OH)2 D
↑bone formation by 24,25-(OH)2 D

Net effect:
↑ serum Ca
↑ serum PO4
Effects of PTH on Ca and PO4 metabolism

Net effect:
1. @ intestine: ↑Ca ↑PO4 absorption
2. @ kidney:
↓Ca ↑PO4 excretion
↑ 1,25-(OH)2 D3 production
3. @ bone:
low PTH dose ↑bone formation
high PTH dose ↑bone resorption

Net effect:
↑ serum Ca
↓ serum PO4 (b/c it binds Ca2+)
↑ 1,25-(OH)2 D3 production (kidney)
organs involved in the regualtion of Calcium homeostasis
1. Intestine
2. Bone
3. Kidney
precursor of vitamin D synthesized in the skin
cholecalciferol, D3
precursor of vitamin D hydroxylated (1st) in the liver
calcifediol, 25(OH) D3
precursor of vitamin D hydroxylated (2nd) in the kidney. Active vitamin D3.
calcitriol, 1,25(OH)2 D3
Feedback loops of regualtion
1. Ca → PTH secretion
2. Ca → Vit. D production
3. GPCR → Ca secretion
4. PO4 → PTH secretion
5. Vit.D → PTH gene transcription