Bone Minerals Flashcards

1
Q

Ions in bone mineral homeostasis

A

Calcium
Phosphate

Bone is principal reservoir for ions
make up matrix that composes bone structure

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2
Q

importance of ion regulation

A

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

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3
Q

bone diseases

A

osteoporosis - bones become weak (low density)
osteopenia - mild step on progression to osteoporosis
osteopetrosis - bone is too dense → subject to breaks (brittle and inflexible

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4
Q

control sites for plasma Ca2+ and PO4 (3-)

A

gut → uptake, excretion
bone = reservoir
kidney → uptake, excretion

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5
Q

bone remodeling

A

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

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6
Q

osteoblasts + osteoclasts

A

osteoblasts: deposition of bone
osteoclasts: resorption of bone

activation of osteoclasts is indirect - hormones (PTH) activate osteoblasts → secrete RANK ligand → activates osteoclasts

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7
Q

Parathyroid hormone

A

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-)

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8
Q

PTH feedback loop

A

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

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9
Q

vitamin D metabolites → metabolism

A

‘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+

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10
Q

vit D metabolites - action

A

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-)

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11
Q

bone remodeling regulation

A

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

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12
Q

secondary regulators of bone mineral homeostasis

A

FGF23
calcitonin
glucocorticoids
estrogens

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13
Q

FGF23

A

inhibits phosphate uptake
inhibits D3 metabolism
inhibits PTH production

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14
Q

calcitonin

A

secreted from thyroid (parafollicular cells)
inhibits bone resorption
inhibits calcium and phosphate reabsorption in kidney

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15
Q

glucocorticoids

A

prolonged administration causes osteoporosis
blocks calcium uptake in gut, promotes excretion in kidney

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16
Q

estrogens

A

prevent bone loss in post-menopausal women
direct effects in bone, prevents PTH-stimulated resorption

17
Q

disruptions of Ca2+ homeostasis

A

normal circulating levels are ~2.2 mM total Ca2+ and ~1mM free Ca2+ = tightly regulated

hypocalcemia
hypercalcemia

18
Q

hypocalcemia

A

low levels of circulating calcium
causes hyperexcitability of cells
unresolved → seizures, muscle spasms

short term resolution: calcium or active D2 metabolite

long term → can develop secondary hyperparathyroidism: due to low plasma Ca2+; will lead to breakdown and weakening of bones
causes: hypoparathyroidism, vit D deficiency

19
Q

Trousseau’s sign

A

calcium’s effect on membrane voltage leads to spasm in hand when pressure is applied to arm

20
Q

hypercalcemia

A

too much circulating Ca2+
loss of cellular excitability → lethargy, coma, pain in bones

primary hyperparathyroidism: overactivity of parathyroid → too much PTH
therapy: resection of gland; therapeutics to protect bone; calcimimetics: negative regulation of parathyroid

21
Q

osteoporosis

A

low bone density → abnormal bone loss → fractures
loss of balance between formation (decline) and resorption (incline) of bone

common in aging females - hormone replacements (risk of cancer); estrogen mimics

causes: long term-glucocorticoid administration; hyperparathyroidism

22
Q

teriparatide

A

therapy for osteoporosis
recombinent, fully active PTH fragment → stimulates osteoblasts without activating osteoclasts to promote deposition rather than resorption

23
Q

biphosphanates

A

therapy for osteoporosis
inhibition of osteoclast resorption of bone

might also inhibit glucocorticoids
side effects

two phosphonate groups
ex. alendronate
phosphate groups have high affinity for Ca2+ → drugs accumulate in bone

24
Q

osteoprotegerin

A

endogenous inhibitor of RANK/RANKL system
binds to RANKL → inhibits stimulation of osteoclasts = inhibition of bone resorption

OPG knockout = decreased expression → low bone density
OPG transgenic = increased (over-) expression → high bone density

25
Q

denosumab

A

osteoprotegerin mimetic
osteoporosis treatment

monoclonal antibody directed against RANKL (mimics effects of OPG) → decoy receptor

promotes protection of bone