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30 Cards in this Set
- Front
- Back
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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. |
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Role of cathespin K |
Digests the organic bone matrix (in the osteoclast) |
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Role of TRAP (tartrate resistant acid phosphate) |
Vesicles rich in TRAP used for exocytosis of bone degradation products through basolateral membrane |
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Effect of estrogen on bone remodelling |
Estrogen provides inhibition of IL-6 (used in osteoclast differentiation). Post menopause results in shift to osteoclastic activity. |
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Effect of glucocorticoids on bone remodelling |
Physiological level: osteoblast activity favoured
Prolonged use: osteoclast activity favoured, decreasing BMD (greater than 3 months of use) |
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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 |
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Effect of prostaglandins on bone remodelling |
PGE2 stimulates resorption and formation of bone.
COX-2 inhibitors shown to have increased fracture risk. |
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Major risk factors of osteoporosis |
Age >65 years Low BMD Glucocorticoid therapy (>3 months) Fragility fracture after 40 Family Hx Primary hyperparathyroidism Malabsorption syndrome |
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Preventative steps towards prevention of osteoporosis |
1. Adequate Ca 2. Adequate active vit D 3. Weight bearing activities |
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Define osteoporosis |
Decrease in BMD When BMD is lost more quickly than it can be replaced |
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T scores |
> -1: normal -1 to -2.5: osteopenia < -2.5: osteoporosis |
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3 groups who should be considered for pharmacological treatment |
1. Minimal trauma fracture (in men >50 and postmenopausal women)
2. BMD score less than -2.5 and no fracture
3. Prolonged glucorticoid therapy (>3 months) |
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4 classes of anti-resorptive agents |
1. Bisphosphonates 2. Denosumab 3. SERMs 4. HRT |
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Anabolic medication to treat osteoporosis |
Teriparatide (synthetic PTH) |
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Dual agent used to treat osteoporosis |
Strontium ranelate |
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Bisphosphonates are analogs of what? Localised to where? |
Analogs of pyrophosphate (P-C-P) Localised to the bone matrix |
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2 types of bisphosphonates, give examples of each. |
1. Non-nitrogen containing Cytotoxic ATP analogues Etidronate
2. Nitrogen containing Interrupts protein prenylation, impaired protein trafficking Alendronate and risedronate |
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Side effects of alendronate |
Dyspepsia Heartburn Irritation of the gastric mucosa Oesophagus Nausea Vomiting |
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MOA of denosumab |
Human IgG1 monoclonal antibody binds RANKL Inhibits RANKL interacting with RANK, inhibits osteoclast differentiation
Injected 1-2 times a year |
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Risks of HRT |
Small increased risk of: Coronary heart disease Breast cancer Thromboembolic disease |
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MOA of SERMs E.g.? |
Varying degrees of estrogen receptor agonist activity Raloxifene is effective at vertebral fracture risk sites, but not effective at non-vertebral sites Agonist: bone Anatagonist: breast and endometrium |
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Where is raloxifene recommended? |
Postmenopausal women: With milder osteoporosis Mainly have vertebral fractures Women at risk of breast cancer (antagonist at ER in breast tissue) |
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Where is HRT recommended? |
Younger postmenopausal women who also have menopausal symptoms |
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Risks of raloxifene |
VTE (similar to HRT) |
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Effect of strontium ranelate
Side effects? |
1. Increases osteoblast differentiation 2. Inhibits osteoclast differentiation
Increased risk of MI |
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Define Paget's disease |
Excessive bone turnover
Causes: Bone deformities Pain Fractures |
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Keys areas of bone affected by PD? |
Skull, spine and pelvis |
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Difference between PD and osteoporosis |
Osteoporosis: generalised decrease in BMD PD: low bone density limited to discrete bones |
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Two things needed to diagnose PD? |
1. Radiology 2. Increased ALP (ALP involved in normal bone growth) |
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Main treatment for PD? |
Bisphosphonates (slows bone remodelling) Stopped when remission (ALP levels) is achieved |
