Bone Minerals Flashcards
what are the 2 main ions in bone mineral homeostasis?
Ca^2+ (mainly) and PO4^3-
where is the principal reservoir for Ca and phosphate?
bone (then ICF and circ)
why is regulation of Ca and PO4 important?
health/strength of bones (long-term), electrical excitability (acute), intracellular signalling for gene expression
what is osteoporosis, osteopenia, and osteopetrosis?
osteoporosis: severe bone density loss (breakable)
osteopenia: decr bone density/softening
osteopetrosis: incr bone density/hardening (breakable)
what are 3 control sites (input/exhaust pathways) for Ca and PO4 plasma levels?
Gut, bone, kidneys
what 2 hormones control Ca and PO4 levels in body?
vitamin D3 and PTH
what is the function of osteoblasts vs osteoclasts?
blasts: bone deposition
clasts: resorption
how do vit D and PTH regulate bone resorption?
hormones activate osteoblasts which secrete RANK ligand (RANKL) and activate osteoclasts (indirect activation)
what is the effect of PTH in bones and kidneys (Ca and PO4 levels)? net?
bones: incr resorption, incr Ca and PO4 levels
kidneys: incr Ca reabsorption and PO4 excretion, incr Ca and decr PO4 (+ stimulates vit D met.)
NET: incr Ca, decr or maintain PO4
what triggers incr PTH secretion from PTG?
decr Ca levels
what is vitamin D?
“steroid” hormone (secosteroid, steroid - 1 ring)
what is the metabolization process of vit D3?
(from diet or sunlight) liver metabolizes vit D3 to 25-OH-D3, kidney metabolizes into active calcitriol (1,25-hydroxy vit D3) or inactive secalciferol (24,25-hydroxy D3)
what is the effect of vit D3 in bones, kidneys, and gut (Ca and PO4 levels)? net?
bones: incr resorption, incr Ca and PO4
kidneys: decr Ca and PO4 excretion, incr Ca and PO4
gut: incr Ca and PO4 absorption, incr Ca and PO4
NET: incr Ca and PO4
what triggers vit D3 conversion to calcitriol (1,25-hydroxy vit D3) vs secalciferol (24,25-hydroxy D3)?
calcitriol: low Ca/high PTH
secalciferol: high Ca/calcitriol (1,25-OH D3)
what senses plasma Ca levels?
Ca receptors in PTG
where are PTH receptors found?
kidney and osteoblasts (bone)
how does PTH affect vit D and thus Ca and PO4 levels?
PTH incr vit D conversion to 1,25 form (active) which incr Ca and PO4 levels (gut, kidneys, and bone)
what are 3 symptoms and 2 treatments for acute hypocalcemia?
symptom: hyperexcitability, Trousseau’s sign (arm muscle contraction w/ BP cuff), seizures/spasms
treatment: Ca or active vit D3 supplement
what is the long-term danger of hypocalcemia?
can develop 2ndary hyperparathyroidism (decr Ca causes constant PTH secretion), consistent breakdown/weakening of bone
what are 2 underlying defects of hypocalcemia?
hypoparathyroidism (fix: Ca/vitD suppl) or vitamin D deficiency (fix: diet, suppl, sunshine)
what are 3 symptoms and 4 treatments for acute hypercalcemia?
symptoms: hypoexcitability, lethargy, bone pain if high PTH (can go into coma)
treatments: resect PTG, vit D supplements, therapeutics to protect bone, calcimimetics
what is a possible underlying defect of hypocalcemia?
primary hyperparathyroidism (tumor?)
what is osteoporosis?
abnormal bone loss that can lead to fractures (slow onset, long-term) - bone is porous
t/f: osteoporosis in common in ageing females
true, b/c decr estrogen
what is a possible treatment for osteoporosis in ageing females?
hormone replacement or estrogen mimetics
what are 2 other causes for osteoporosis? (not female ageing)
long-term glucocorticoid administration, hyperparathyroidism
what is teriparatide?
recombinant, fully active PTH fragment (1-34)
how does teriparatide (PTH fragment) treat osteoporosis if PTH incr bone resorption?
given in a pulsatile manner to stimulate bone deposition by osteoblasts (have PTH Rs) wo/ stimulating osteoclasts indirectly via RANKL
what are bisphosphonates?
inhibitors of osteoclast resorption of bone (cause apoptosis)
what are 3 possible side effects of bisphosphonates?
cancer, fractures, GC inhibition
what is the general structure of bisphosphonates?
two phosphonate groups (pyrophosphate)
what is the most commonly prescribed bisphosphonate?
alendronate
what allows bisphosphonates to accumulate in bone?
PO4- groups have a high affinity for Ca2+ (can target osteoclasts)
what is osteoprotenerin?
endogenous RANKL inhibitor (binds to RANKL)
what is the effect of osteoprotegerin?
prevents RANKL from binding and activating osteoclasts, which decr bone resorption
what is denosumab?
monoclonal Ab that inhibits RANKL (~osteoprotegerin)
