Kinder, bone mineral homeostasis part II Flashcards
what normally makes calcitonin
parafolicular cells of the thyroid
principle effects of calcitonin
decrease serum Ca and PO4 by actions on bone and kidney
calcitonin effects on bone
inhibits osteoclastic bone resorption
in time formation reduced as well
calcitonin effects on kidney
dec Ca and PO4 resorption as well as reabsorption of Na K and Mg
therapeutic use of calcitonin
disorders of increased skeletal remodeling (pagets and osteoporosis)
adverse effects of calcitonin
nausea, hand swelling, urticaria, and intestinal cramping
glucocorticoids actions in bone remodeling
antagonize vit D stimulated intestinal Ca transport, stimulate renal Ca excretion and block bone formation
decrease in total body Ca stores
therapeutic use of glucocorticoids
reversing hyperCa assoc with lymphomas and granulomatous disease like sarcoidosis or in vit D intoxication
prolonged administration of glucocorticoids can cause what
osteoporosis in adults and stunted skel muscle development in children
how do estrogens affect bone
prevent accelerated bone loss during the immediate post-menopausal period
transiently increase bone in post menopausal women
how does raloxifene work
partial agonist in bone but does not stimulate endometrial proliferation in post menopausal women
therapeutic use of raloxifene
Tx and prevention post menopausal osteoporosis
adverse effects of raloxifene
hot flashes, leg cramps, thromboembolism
contraindications of raloxifene
women with active or pasty history of venous thromboembolism and women with CHD or risk facotrs for major coronary events including stroke
MOA aldendronate (bisphosphanate)
analogs of pyrophosphate in which P-O-P is replaced with non hydrolyzable P-C-P bond
where does alendronate concentrate
sites of active bone remodeling, incorporated into bone until the bone is remodeled and the bisphosphonate is released back into the acid mdeium
alendronate effects on osteoclasts
directly inhibits
when should patients take alendronate
with full glass of water at least 30 minutes prior to first meal
therapeutic use of alendronate
osteoporosis, hyper Ca, Pagets
adverse effects of alendronate
esophageal and gastric irritation (take with water)
subtrochanteric femur fractures from over suppression of bone turnover
MOA denosumab
monoclonal Ab that prevents action of RANKL by binding it
therapeutic use denosumab
post-menopausal osteoporosis and some cancers (prostate and breast)
how is denosumab administered
SQ every 6 mo
adverse effects of denosumab
increased risk infection because many other cells ahve RANKL
osteonecrosis of jaw and subtrochanteric fractures
can lead to transient hypoCa or comprised Ca regulatory mech like chronic kidney disease and Vit D deficiency
signs of hyperCa
CNS depression, coma, death
major causes Hyper Ca
thiazie Tx, hyper PTH and cancer
less common causes of hyper Ca
hypercitaminosis D, sarcoidosis, thyrotoxicosis, milk alkali syndrome, adrenal insufficiency and immobilization
Tx approach to hyper Ca
saline diuresis bisphosphonates calcitonin phosphate glucocorticoids
why is saline diuresis used in hyper Ca
Most patients with severe hypercalcemia have a substantial component of prerenal azotemia due to dehydration which prevents kidney from compensating for the rise in serum calcium by excreting more calcium in the urine.
calcitonin use in hyper Ca
Seldom restores calcium to normal but lack of toxicity permits frequent administration at high doses. Effects seen within 4-6 hours, lasts 6-10 hours.
phosphate use in hyper Ca
Fastest way to decrease serum calcium but hazardous if not done properly. Give IV phosphates slowly over 6-8 hours and switch to oral products once symptoms clear.
Risks associated with IV phosphates
sudden hypocalcemia, ectopic calcification, acute renal failure, hypotension.
role of glucocorticoids in hyper Ca
no clear role
main features of hypoCa
neuromuscular tetany paresthesias, laryngospasm, muscle cramps, seizures
major causes hypoCa
hypoPTH, Vit D def, chronic kidney disease and malabsorption
Tx approach to hypoCa
Ca IV, IM PO
VIT D, calcitriol when need rapid action
why do we do slow infusions of Ca gluconate in severe hypoCa
to prevent cardiac arrhythmias
what is used for IV Ca
Ca gluconate because less irritating to veins than Ca Cl
what are the oral formulations fo Ca
Ca carbonate
Ca lactate
Ca PO4
Ca citrate
what is the preferred oral Ca
Ca carbonate because high % of Ca, avaialble, low cost and antacid properties
hyperPO4 is a common ocmplicaiton of what
renal failure
hypoPTH
Vit D intoxication and tumoral calcinosis
what is Tx for hyperPO4
dietary restriction and use of PO4-binding gels like sevelamer and Ca supplements
what to avoid in hyperPO4
aluminum containing antacids because can cause aluminum assoc bone disease
Tx primary hyperPTH
surgery, vit D supp
Tx secondary hyperPTH
cinacalcet
Tx hypoPTH
Ca and Vit D supp
Tx Vit D deficiency
Vit D replacement
Tx options for osteoporosis
bisphosphonates SERMs Ca and Vit D supp teriparatide calcitonin denosumab
What is used to Tx Pagets
Calcitonin and bisphosphanates are first line agents
Tx with bisphosphanates should not exceed what time period
6 mo, but can be repeated after “holiday” from drug
