- increase both osteoclasts and osteoblasts in bone via RANKL and TNF cytokine. - couples Gs receptors to increase cAMP in bone and renal tubular cells.

Bone Minteral Homeostasis Flashcards by Erik Mai

what are the effects of PTH in the kidney?

decrease phosphate reabsorption
increase Ca reabsorption
increase 1,25-OH2-D3 formation

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what is the effect of PTH on Ca and Phosphate?

Kidney:

decrease phosphate reabsorption -> decrease plasma phosphate
increase Ca reabsorption -> increase plasma Ca
increase 1,25-OH2-D3 formation -> increase intestinal Ca absorption
- > increase plasma Ca

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what is the effect on calcium and phosphate in the presence of calcitonin?

Kidney:
decrease phosphate reabsorption -> decrease plasma phosphate
decrease Ca reabsorption -> decrease plasma Ca

Bone:
decrease bone resorption -> decrease plasma Ca

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What is the role of Mg in PTH secretion?

moderate decline in Mg -> enhance in PTH secretion

2. severe decline in Mg -> decrease PTH secretion

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what are the common causes of decreased Mg?

chronic diarrhea
diuretics
EtOH abuse
Chronic PPI and aminoglycoside use.

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what are the sources of Vit D?

sunlight and dietary intake.

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what is the active form of vit d?

what is the pathway?

calcitriol (1,25 dihydroxy cholecalciferol)
7-dehydrocholeseterol -[sunlight]-> cholecalciferol (vit D3) -[25-hydroxylase]-> 25-hydroxyvitD3 -[1alpha-hydroylase]-> 1,25 dihydroxyvitD3

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what is Ergocalciferol?

dietary intake of VitD2 and VitD3.

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what are the effects of 1,25-dihydroxycholecalciferol?

kidneys:

increase phosphate reabsorption -> increase plasma phosphate
increase Ca reabsorption -> increase plasma Ca

Intestine:

increase phosphate absorption -> increase plasma phosphate
increase Ca absorption -> increase plasma Ca

bone:
promote PTH action -> increase Ca plasma

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what are the hormonal regulators of bone mineral homeostasis?

PTH
VitD
calcitonin
estrogen
glucocorticoids

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what are the non-hormonal regulators of bone mineral homeostasis?

bisphosphonates
fluoride
calcimimetics

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actions of PTH?

increase both osteoclasts and osteoblasts in bone via RANKL and TNF cytokine.
couples Gs receptors to increase cAMP in bone and renal tubular cells.

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WHat is a recombinant PTH?

Teriparatide

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Teriparatide

PD?

pulsatile doses: stimulate bone formation

high doses: bone resorption

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Teriparatide

clinical applications?

osteoporosis

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Teriparatide

A.E?

hypercalcemia

hypercalciuria

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what is a RANKL inhibitor?

Denosumab

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Denosumab

MOA?

binds c RANKL and prevents stimulating osteoclast differentiation and function.
inhibit bone resportion

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Denosumab

clinical applications?

osteoporosis

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Denosumab

A.E?

risks of infxn

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Vit D

MOA?

activate steroidal nuclear receptor

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What are the two types of VitD dependent rickets?

type I - defect 1alpha hydroxylase enzyme -> decrease calcitriol -> decrease Ca and P

Type II - defective receptor for vitD

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What is used to treat secondary hyperparathyroidism in pts c chronic renal disease and liver disease?

calcitriol

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What is used for the tx of psoriasis (topical application)?

Calcipotriol

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what are vitD supplements used for?

osteoporosis chronic renal failure nutritional rickets d/t inadequate intake chronic liver disease

vit D ADR?

chronic over dose = hypercalcemia and hyperphosphatemia

what is the level of Ca and PTH in primary hyperparathyroidism?

high PTH | high Ca

what is the level of Ca and PTH in seconday hyperparathyroidism?

high PTH | low or normal Ca

what causes secondary hyperparathyroidism?

Vit D deficiency | Chronic renal failure.

what is vitD3 generic name?

cholecalciferol

what is vitD2 generic name?

ergocalciferol

what is 1,25-dihydroxyvitD3 generic name?

calcitriol

what is 1alpha-hydroxyvitD2 generic name?

doxercalciferol

what is 19-nor-1,25dihydroxyvitD2 generic name?

paricalcitol

what is calcipotriene generic name?

calcipotriol

what is a phosphate binding drug?

sevelamer

Sevelamer clinical applications?

prev hyperphosphatemia in pts c chronic renal failure.

sevelamer MOA?

binds to P and prev absorption in GI

What are some Ca oral preps?

Ca carbonate Ca citrate Ca lactate

what are some Ca IV preps and tx?

Clacium gluconate tx: hypocalcemic tetany counteract overdose of Mg sulfate used in eclampsia

calcium preps A.E?

``` IM = necrosis and abscess formation IV = thrombophlebitis ```

Calcitonin clinical applications?

osteoporosis | increase bone mass and reduce spine fractures

Salmon Calcitonin PK?

longer half life and greater potency Injxn and nasal spray

Estrogens clinical applications?

prev bone loss osteoporosis in post menopausal women given as hormonal replacement therapy

estrogens A.E?

thromboembolism migraine increase risk of breast and endometrial cancer

tamoxifen MOA?

estrogen antagonist in breast | agonist in bone and uterus

tamoxifen clinical applications?

breast cancer | beneficial effect on bone

tamoxifen ADR?

increased risk of endometrial cancer thromboembolism hot flushes

Raloxifene MOA?

estrogen antagonistic on breast | agonist on bone

raloxifene clinical applications?

osteoporosis in post-menopausal women

raloxifene ADR?

thromboembolism | hot flushes

what are some Bisphosphates?

1. Etidronate (not for long term use) 2. Alendronate 3. Pamidronate (i.v) 4. Risedronate

1. Etidronate 2. Alendronate 3. Pamidronate 4. Risedronate MOA?

inhibit osteoclastic activity via decrease farnesyl pyrophosphate syn by disrupting mevalonate pathway decrease osteoclast H ATPas. reduce resorption helps formation of hydroxyapatite

what drug results in bone malformation decrease osteoblastic activity if long term use?

etidronate

1. Etidronate 2. Alendronate 3. Pamidronate 4. Risedronate clinical applications?

osteoporosis malig assoc hypercalcemia Paget's disease of bone

what is Paget's disease?

increased turnover c extreme bone resorption and excessive bone formation. presentation: aching bone and joint pain or fractures

1. Etidronate 2. Alendronate 3. Pamidronate 4. Risedronate A.E?

erosive esophagitis d/t direct irritation - prev by upright position after taking rx - increase fluid intake

which bisphosphonates is assoc c osteomalacia, osteonecrosis of jaw and fractures?

etidronate

Cinacalcet MOA?

activates Ca-sensing receptors in parathyroid cells, leading to decrease in PTH syn and release

cinacalcet clinical applications?

secondary hyperparathyroidism in chronic renal disease | hyperparathyroidism in pts c parathyroid cacinoma

cinacalcet A.E?

nausea | hypocalcemia

Fluoride (rx affecting calcium homeostasis) A.E?

new bone synthesis which is denser but brittle.

gallium nitrate (rx affecting calcium homeostasis) MOA? clinical applications? A.E?

1. inhibits bone resorption 2. tx: cancer related hypercalcemia 3. Nephrotoxicity

plicamycin (mithracin) - (rx affecting calcium homeostasis) MOA? clinical applications? ADR?

1. cytotoxic anticancer rx 2. cancer-related hypercalcemia 3. thrombocytopenia, hepatic and renal toxicity

what are the drugs causing osteoporosis?

``` corticosteroids heparin lithium anastrozole alcohol ```

what are the drugs causing osteomalacia?

phenytoin | etidronate (>12mos use)

what are drugs prev Ca excretion? what is it used for? what is the clinical application of the drug?

thiazide diuretics - increasing reabsorption prev renal stone formation tx: htn in osteoporosis pt

what are the tx's for hypercalcemia?

furosemide & saline infusion bisphosphonates Calcitonin Parathyroidectomy

tx of osteoporosis?

``` stop smoking, EtOH abuse, and corticosteroid HRT - in sx perimenopausal period Ca & vitD suppl. bisphosphonates SERMs teriparatide ```

what is the remodeling cycle for bones?

Osteoclast activity = resorption | Osteoblast activity = deposit new bone to restore integrity

Bone Minteral Homeostasis Flashcards

(70 cards)