Bone Homoestasis Dr. Pond Flashcards
EXAM 2
Risk factors for Osteoporosis in females
Age: over 50 -> menopause
lower body weight and muscle mass
early menopause: low estrogen
no pregnancy: low estrogen
Risk factors for Osteoporosis in males
-age: over 50
-short statue, thin build
-weak hip muscles
-low tesosterone
Other risk factors
caffeine
depression
low vitamin D and calcium
certain meds
Which medication increases the risk for osteoprosis?
Corticosteroids
-decreases organic matter in bones
-decreases calcium and phosphates in bones
What is the organic matrix in the bone?
Osteoid (95% collagen, 5% ground substance - mixture of proteoglycans)
What is the inorganic matrix in the bone?
-Hydroxyapatite
-other minerals
build on top of organic matrix
Function of Osteoblasts
synthesize Osteoids
-> Hydroxyapatite get deposited on it
Osteoblasts get trapped together with hydroxyapatite in the bone they are forming
->no longer active in bone production -> they become the resident bone cells (osteocytes)
Function of Osteoclasts
Bone resorption
secretes proteases -> breaking down the osteoids
secretes acids dissolves hydroxyapatite
How does PTH affect Ca2+, PO4(3-)?
-increases Ca2+
-decreases PO4(3-)
stimulates the production of active Vitamin D ->
Vitamin D has to be formed into the active form
How does Vitamin D affect Ca2+, PO4(3-)?
-increases Ca2+
-increases PO4(3-)
inhibits the production of PTH -> negative feedback loop to PTH
stimulates FGF-23
How does Fibroblast growth factor 23 affect Ca2+, PO4(3-)?
only decreases PO4(3-)
inhibits production of active Vitamin D -> negative feedback loop to Vitamin D
What is the role of calcitonin?
-decreases Ca2+ in the plasma
-decreases PO4(3-) in the plasma
-> works on osteoclasts -> stimulates resorption and keeps Ca and PO4(-3) in the bone (levels go down in the serum)
other secondary regulators are:
prolactin, growth hormone, insulin, thyroid hormone, glucocorticoids, sex steroids
On which organ does PTH work?
Kidney
increases reabsorption of Ca2+
decreases reabsorption of PO3(-4) -> more excretion
also works in the bones
What is PTH’s effect on the bone?
increasing resorption (bone breakdown) -> it is going to free up Ca and PO (Ca levels go up, PO4(3-) will be exerted)
On which organ does Viramin D work?
The gut
increases absorption of Ca2+
increases absorption of PO3(-4)
through upregulation of their transporters
Kidney:
Vitamin D can also inhibit the urine output of Ca2+ and PO3(-4) –> but that’s a weaker effect
On which organ does FGF-23 work?
in the kidneys:
decreases reabsorption of PO3(-4)
some activity in the bones
On which organ does Calcitonin work?
mainly in the bone
decreases bone resorption -> more Ca2+ and PO3(-4) stays in the bone -> less coming out of the bone into the serum -> decrease Ca2+ and PO3(-4) serum levels
some activity in the kidneys
-> more elimination of Ca2+ and PO4(3-)
How do Ca2+ levels regulate PTH?
high levels of Ca2+ –> decreases PTH
as Ca2+ goes up it actives the Ca-sensitive protease
-> the protease cleaves PTH (peptide hormone) into fragments
as Ca2+ goes up it binds to CaR -> decreases PTH release from the parathyroid gland
How does PO4(-3) regulate PTH?
high Phosphate levels stimulate PTH production
as PO4(-3) goes up it binds to Ca2+ and forms calcium phosphate -> which will reduce free calcium -> there is less calcium binding CaR on the parathyroid gland
-> which will stimulate PTH production
What is the mechanism of PTH’s effect on the bone?
PTH induces RANKL (ligand) from osteoblasts
-> RANKL binds on RANK (receptor) on osteoclast precursor -> activation of osteoclasts -> RESORPTION (bone breakdown)
-> increase in free Ca and PO4(-3)