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3 ion channels found in the osteoclast
1. HCO3-/Cl- exchangers
Cl- moves in and HCO3- moves out of the cell
2. ATP H+ pump
H+ pumped through the ruffled membrane into the pocket of acidification
3. CLCN7
Cl- moves through ruffled membrane into pocket of acidification
HCl formed to dissolve hydroxyapatite.
Role of cathespin K
Digests the organic bone matrix (in the osteoclast)
Role of TRAP (tartrate resistant acid phosphate)
Vesicles rich in TRAP used for exocytosis of bone degradation products through basolateral membrane
Effect of estrogen on bone remodelling
Estrogen provides inhibition of IL-6 (used in osteoclast differentiation).
Post menopause results in shift to osteoclastic activity.
Effect of glucocorticoids on bone remodelling
Physiological level: osteoblast activity favoured
Prolonged use: osteoclast activity favoured, decreasing BMD (greater than 3 months of use)
Effect of PTH on bone remodelling
Acute doses: osteoblast activity favoured
Endogenous: osteoclast activity favoured, Ca movement from bone fluid to blood, reabsorption at the kidneys
Effect of prostaglandins on bone remodelling
PGE2 stimulates resorption and formation of bone.
COX-2 inhibitors shown to have increased fracture risk.
Major risk factors of osteoporosis
Age >65 years
Low BMD
Glucocorticoid therapy (>3 months)
Fragility fracture after 40
Family Hx
Primary hyperparathyroidism
Malabsorption syndrome
Preventative steps towards prevention of osteoporosis
1. Adequate Ca
2. Adequate active vit D
3. Weight bearing activities
Define osteoporosis
Decrease in BMD
When BMD is lost more quickly than it can be replaced
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