Bone Mineral Homeostasis Flashcards by Vanessa Nwaokocha

what stimulates thyroid gland to secrete calcitonin and what stimulates it to secrete PTH?

Parafollicular C cells –> calcitonin –> reduce uptake of Ca2+ –> decreased plasma Ca2+

Parathyroid Chief cells –> PTH –> increase uptake of Ca2+ –> increased plasma Ca2+

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how does PTH affect plasma phosphate

PTH works on kidney to reduce phosphate reabsorption –> increased urinary phosphate –> decreased plasma phosphate

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how does calcitonin affect plasma phosphate

increased plasma calcitonin works on kidney to decrease both calcium and phosphate reabsorption –> increased urinary phosphate –> decreased plasma phosphate

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how does magnesium affect PTH secretion

moderate decline in Mg –> enhanced PTH secretion

- severe decline in Mg –> decreased PTH secretion

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what are common causes of decreased magnesium

CADCA

Chronic Diarrhea
Alcohol Abuse
Diuretics
Chronic PPI
Aminoglycoside use

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mechanism of vitamin D’s transformation to its active form

vitamin D (taken up by skin from sun) uses 7-dehydrocholesterol –> Cholecalciferol (vitamin D3) uses 25 hydroxylase in liver –> 25-hydroxyvitamin D3 uses 1 alpha hydroxylase in kidney —> 1, 25-dihydroxycholecalciferol aka calcitriol

or get vitamin D from diet in form of ergocalciferol (vitamin D2) or vitamin D3 which is taken up by liver and using 25 hydroxylase –> 25 hydroxyvitamin D3 which uses 1 alpha hydroxylase in kidney –> 1, 25 dihydroxycholecalciferol aka calcitriol

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what is the effect of 1,25-dihydroxycholecalciferol aka calcitriol on calcium and phosphate metabolism

in bone promotes PTH secretion
in intestine –> increases calcium and phosphate absorption
in kidney –> increases calcium and phosphate reabsorption

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what produces fibroblast growth factor 23

osteoblasts and osteoclasts

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what is the function of fibroblast growth factor 23

inhibits calcitriol production and phosphate reabsorption in kidney –> increased phosphate excretion by kidney –> reduced serum phosphate

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what are the non hormonal regulators of bone mineral homeostasis

Biphosphonates
Fluoride
Calcimimetics

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what are the hormonal regulators of bone mineral homeostasis

Vitamin D
PTH
Calcitonin
Estrogen
Glucocorticoids

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how does PTH increase osteoclast AND osteoblast activity in bone

via ligand RANKL, a TNF cytokine

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mechanism of PTH

couples Gs receptors and increases cAMP in bone and renal tubular cells –> bone resorption

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recombinant PTH analogue

Teriparatide

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how does the doses of the PTH analogue stimulate different function (name it)

Teriparatide

pulsatile doses –> bone formation
large does –> resorption aka bone breakdown to increase calcium

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function of Teriparatide

Osteoporosis (pulsatile dose)

- Restores normal bone loss

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AE of Teriparatide

Hypercalcemia
Hypercalciuria

If used for longer than 2 years: increased risk of osteosarcoma

what is the RANKL (RANK ligand) inhibitor and what is its mechanism

Denosumab –> monoclonal antibody that binds to RANKL –> prevents it from binding and stimulating osteoclastic (RANK) activity

use of Denosumab

used to inhibit bone resorption hence treating osteoporosis

AE of denosumab

increased risk of infections

what are the two types of Vitamin D dependent Rickets

Type I: defective 1 alpha hydroxylase enzyme –> reduced calcitriol –> decreased calcium and phosphate

Type II: defective receptor for vitamin D

what is Calcitriol used to treat

secondary hyperparathyroidism in patients with chronic renal failure and liver disease

what is Calcipotriol used to treat (what is chemical name for it)

Calcipotriene

psoriasis (topical application)

who are vitamin D supplements given to (name the vitamin D given)

Vitamin D2 - Ergocalciferol
Vitamin D3 - Cholecalciferol

Chronic renal failure
Osteoporosis
Nutritional rickets with inadequate intake
Chronic Liver failure

AE of vitamin D

chronic over dose --> hypercalcemia and hyperphosphatemia

name the phosphate binding drug and what it is used for

Sevelamer --> prevent hyperphosphatemia in those with chronic renal failure and can't excrete the phosphate binds phosphate and prevents reabsorption in GI

oral calcium prep and what it is used for

Oral: Ca carbonate, Ca citrate, Ca lactate counteract overdose of magnesium sulfate used in eclampsia

IV calcium prep and what it is used for

Calcium gluconate -- used for hypocalcemic tetany

AE of calcium preps

IM: necrosis and abscess formation IV: thrombophlebitis

form of calcitonin that has a longer half life and potency? what it is used for?

Salmon calcitonin --> osteoporosis; increases bone mass and decreases spine fractures

role of estrogen in bone mass

if given can reduce the amount of bone mass loss --> used in post menopausal women as a HRT and is more of a preventative measure

AE of estrogen

Thromboembolism Migraine Increased risk of breast and endometrial cancer

SERMs role in bone mass (Selective estrogen receptor modulators)

Tamoxifen: antagonist in breast but agonist in bone and endometrium Raloxifene: antagonist in breast but agonist in bone; no effect in endometrium both have beneficial effect in the bone

AE of SERMS

- Tamoxifen: endometrial cancer, thromboembolism, hot flushes - Raloxifene: thromboembolism, hot flushes

what are the bisphosphonates

RAPE Risedronate Alendronate Pamidronate Etidronate

mechanism of bisphosphonates (name them)

RAPE: Risedronate, Alendronate, Pamidronate, Etidronate - decrease osteoclast H+ ATPase --> disrupt mevalonate pathway --> decreases farnesyl pyrophosphate synthesis --> inhibits osteoclastic activity - bind with hydroxyapatite in bone --> reduce resorption

uses of bisphosphonates (name them)

RAPE: risedronate, alendronate, pamidronate, etidronate Osteoporosis, malignancy associated hypercalcemia, Paget's disease of the bone

why is there a history of ache, joint pain, or fractures in those that have paget's disease

due to latent viral infection and association with genetic cause - chromosome 5 and 6

which bisphosphonate is used for glucocorticoid induced osteoporosis

Alendronate

AE of bisphosphonates

Erosive Esophagitis (direct irritation to lining) Etridonate: Osteomalacia, Osteonecrosis of jaw and fractures Chronic Etridonate and Pamidronate: bone malformation due to reduced osteoblastic activity

how do you reduce the erosive esophagitis seen as AE of bisphosphonates

RAPE: risedronate, alendronate, pamidronate, etidronate upright position after taking medication increase fluid intake