Limbs and Back: Week One Flashcards
What is the effect of CBFA1?
Mesenchymal differentiation into osteoblast precursor
What is OPG?
A decoy receptor preventing RANKL binding and osteoclast activity
Name five things that osteoblast secret
- Type I collagen
- Type V collagen
- Osteonectin
- Osteopontin
- Osteoprotegerin
Name the forms of vitamin D
- Vitamin D2 (ergocalciferol) from plants
- Vitamin D3 (cholecalciferol) from animals
Name the two ways in which vitamin D3 can be obtained
- UV radiation converts 7-dehydrocholoesterol into vitamin D3 (endogenous)
- Obtained from the diet (exogenous)
Describe the process of active Vitamin D formation in the body
- Vitamin D3 is transported in chylomicrons and it will bind to DBP protein
- This complex will travel to the liver and meets the enzyme 25-hydroxylase. This forms 25-hydroxy vitamin D.
- This travels to the kidney to meet the enzyme 1-alpha-hydroxylase and this forms 1.25-dihydroxyvitamin D.
Name three ways in which 1-alpha-hydroxylase activity is stimulated.
- induced by PTH
- hypocalcaemia
- hypophosphatemia
Give three functions of vitamin D
- Forms calcium channels in the intestine resulting in increased calcium absorption in the intestine
- Forms calcium channels in the kidney and this will increase calcium absorption
- Increase expression of RANKL on osteoblasts and causes increased differentiation of pre-osteoclasts
Name two things that mature osteoclasts secret
- Hydrochloric acid
- Cathepsin K
What does RANKL stand for?
Receptor activator of nuclear factor kappa B ligand
What is the difference between Rickets and Osteomalacia?
Rickets occurs in children. Symptoms include occipital bone flattening, frontal bossing, square head, rachitic rosary, pigeon breast and lumbar lordosis.
Osteomalacia occur in adults and increases the risk of getting fractures.
What is Osteoporosis?
A condition that weakens the bones, making them fragile and likely to break.
Bone density will fall 2.5 standard deviations below the mean for young adults of same sex.
Give some risk factors of Osteoporosis
- over 70 years
- menopause under 40
- anorexia
- glucocosteroids
- smoking
- alcohol
- obesity
- oestrogen deficiency
- low calcium
What are the serum results from Osteoporosis?
Calcium, Phosphate, ALK Phosphate and PTH are normal.
Bisphosphonates are drugs used to treat osteoporosis. There are three generations. Give examples and the mechanism of action for the first generation.
Examples include Etidronate. These drugs are non-nitrogen containing and incorporated into ATP and interfere with ATP-dependent pathways, causing apoptosis.
Bisphosphonates are drugs used to treat osteoporosis. There are three generations. Give examples and the mechanism of action for the second generation.
Examples include alendronate. These drugs are nitrogen containing. They inhibit osteoclast farnesyl pyrophosphate synthase and prevent protien prenylation required for GTPase formation and therefore inducing apoptosis.
Bisphosphonates are drugs used to treat osteoporosis. There are three generations. Give examples and the mechanism of action for the third generation.
Examples include risedronate and zoledronic acid. These drugs are nitrogen containing. They inhibit osteoclast farnesyl pyrophosphate synthase and prevent protien prenylation required for GTPase formation and therefore inducing apoptosis.
Give the mechanism of action of Raloxifene.
Binds to oestrogen recepotrs and produces oestrogen -like effects and hence slows bone loss.
Give the mechanism of action of Teriparatide.
Portion of PTH that activates osteoblasts.
Give the mechanism of action of Strontium ranelate
Enhances osteoblasts to express for OPG and less RANKL
Give the mechanism of action of Denosumab
Inhibits RANKL expression
Describe Type One osteoporosis
This is due to oestrogen deficiency. There is increased sensitivity to PTH hormones and this leads to increased resorption. There is also a decrease in transforming GF by osteoblasts, increased IL-6 mediated osteoclast differentiation and an increase in lysosomal production.
Describe Type Two osteoporosis
This is known as Senile Osteoporosis and is a result of increasing age (usually over 70). There is decreased ability of the kidneys to produce 1.25-dhyrdroxyvitamin D and hence decreased calcium absorption. There will therefore be an increase in PTH.
Describe the distribution of calcium in the body
99% of calcium is found in bone in the form of hydroxyapatite. The 1% in the serum is split into three:
- 50% ionized (only one physiologically active)
- 40% bound to albumin
- 10% complexed to anions