Bone Minerals Flashcards
Ions in bone mineral homeostasis
Calcium
Phosphate
Bone is principal reservoir for ions
make up matrix that composes bone structure
importance of ion regulation
health/strength of bones - osteoporosis, osteopenia, osteopetrosis
Ca2+ balance - binds to membrane glycoproteins to impact electrical excitability of cells
Ca2+ = intracellular signal that can regulate expression of genes
bone diseases
osteoporosis - bones become weak (low density)
osteopenia - mild step on progression to osteoporosis
osteopetrosis - bone is too dense → subject to breaks (brittle and inflexible
control sites for plasma Ca2+ and PO4 (3-)
gut → uptake, excretion
bone = reservoir
kidney → uptake, excretion
bone remodeling
bone is dynamic tissue → regenerated and resorbed
vitamin D metabolites and PTH are regulators of bone remodeling → stimulate bone resorption
resorption: release of Ca2+/PO4(3-) from bone
osteoblasts + osteoclasts
osteoblasts: deposition of bone
osteoclasts: resorption of bone
activation of osteoclasts is indirect - hormones (PTH) activate osteoblasts → secrete RANK ligand → activates osteoclasts
Parathyroid hormone
peptide hormone
bone: promotes bone resorption (through RANKL) = increases Ca2+, increases PO4 (3-)
kidney: stimulates vitD processing, promotes Ca2+ absorption, PO4 (3-) excretion = increases Ca2+, decreases PO4 (3-)
PTH feedback loop
receptors on parathyroid gland sense decrease in circulating Ca2+ → release PTH
stimulates bone resorption, kidney reabsorption of Ca2+ and excretion of PO4(3-)
circulating levels of Ca2+ increase → relieves signal
vitamin D metabolites → metabolism
‘steroid’ hormone - missing ring
metabolized in liver (add OH) then kidney to generate:
- calcitriol (active form) if low Ca2+ and high PTH
- secalciferol (weak activity) if high Ca2+
vit D metabolites - action
kidney: decreased Ca2+ and PO4(3-) excretion = increases Ca2+, increases PO4 (3-)
bone: promotes bone resorption = increases Ca2+, increases PO4 (3-)
gut: promotes uptake of Ca2+ and PO4(3-) = increases Ca2+, increases PO4 (3-)
bone remodeling regulation
Ca2+ levels are sensed by Ca2+ receptors on parathyroid and regulated
PTH acts on receptors in kidney and osteoblasts; stimulates Vitamin D metabolism → vitD effects in gut, kidney, bone
= restoration of circulating Ca2+ to normal levels
secondary regulators of bone mineral homeostasis
FGF23
calcitonin
glucocorticoids
estrogens
FGF23
inhibits phosphate uptake
inhibits D3 metabolism
inhibits PTH production
calcitonin
secreted from thyroid (parafollicular cells)
inhibits bone resorption
inhibits calcium and phosphate reabsorption in kidney
glucocorticoids
prolonged administration causes osteoporosis
blocks calcium uptake in gut, promotes excretion in kidney