Bone Minteral Homeostasis Flashcards
what are the effects of PTH in the kidney?
decrease phosphate reabsorption
increase Ca reabsorption
increase 1,25-OH2-D3 formation
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
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
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
what are the common causes of decreased Mg?
chronic diarrhea
diuretics
EtOH abuse
Chronic PPI and aminoglycoside use.
what are the sources of Vit D?
sunlight and dietary intake.
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
what is Ergocalciferol?
dietary intake of VitD2 and VitD3.
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
what are the hormonal regulators of bone mineral homeostasis?
PTH VitD calcitonin estrogen glucocorticoids
what are the non-hormonal regulators of bone mineral homeostasis?
bisphosphonates
fluoride
calcimimetics
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.
WHat is a recombinant PTH?
Teriparatide
Teriparatide
PD?
pulsatile doses: stimulate bone formation
high doses: bone resorption
Teriparatide
clinical applications?
osteoporosis
Teriparatide
A.E?
hypercalcemia
hypercalciuria
what is a RANKL inhibitor?
Denosumab
Denosumab
MOA?
binds c RANKL and prevents stimulating osteoclast differentiation and function.
inhibit bone resportion
Denosumab
clinical applications?
osteoporosis
Denosumab
A.E?
risks of infxn
Vit D
MOA?
activate steroidal nuclear receptor
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
What is used to treat secondary hyperparathyroidism in pts c chronic renal disease and liver disease?
calcitriol
What is used for the tx of psoriasis (topical application)?
Calcipotriol
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?
- Etidronate (not for long term use)
- Alendronate
- Pamidronate (i.v)
- Risedronate
- Etidronate
- Alendronate
- Pamidronate
- 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
- Etidronate
- Alendronate
- Pamidronate
- 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
- Etidronate
- Alendronate
- Pamidronate
- 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?
- inhibits bone resorption
- tx: cancer related hypercalcemia
- Nephrotoxicity
plicamycin (mithracin) - (rx affecting calcium homeostasis)
MOA?
clinical applications?
ADR?
- cytotoxic anticancer rx
- cancer-related hypercalcemia
- 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
