Bone Mineral Homeostasis Flashcards
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+
how does PTH affect plasma phosphate
PTH works on kidney to reduce phosphate reabsorption –> increased urinary phosphate –> decreased plasma phosphate
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
how does magnesium affect PTH secretion
- moderate decline in Mg –> enhanced PTH secretion
- severe decline in Mg –> decreased PTH secretion
what are common causes of decreased magnesium
CADCA
Chronic Diarrhea Alcohol Abuse Diuretics Chronic PPI Aminoglycoside use
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
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
what produces fibroblast growth factor 23
osteoblasts and osteoclasts
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
what are the non hormonal regulators of bone mineral homeostasis
Biphosphonates
Fluoride
Calcimimetics
what are the hormonal regulators of bone mineral homeostasis
Vitamin D PTH Calcitonin Estrogen Glucocorticoids
how does PTH increase osteoclast AND osteoblast activity in bone
via ligand RANKL, a TNF cytokine
mechanism of PTH
couples Gs receptors and increases cAMP in bone and renal tubular cells –> bone resorption
recombinant PTH analogue
Teriparatide
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
function of Teriparatide
- Osteoporosis (pulsatile dose)
- Restores normal bone loss
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
