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
How is phosphate stored in the body?
Most is in the form of hydroxyapatite.
Other forms include the intracellular component of DNA, RNA and cell membranes. There is a small amount existing as inorganic phosphate and phospholipids.
What is PTH
- 84 amino-acid polypeptide
- Produced by chief cells of parathyroid gland
Net effect is to increase calcium and decrease phosphate.
What is calcitriol?
1.23-dihydroxyvitamin D
When is PTH secreted?
It is secreted when there is a lowered calcium.
A significant magnesium depletion can caused decreased PTH secretion.
Describe the negative feedback response of calcitriol.
When calcitriol is synthesized, one molecule will inhibit one molecule on 1-alpha-hydroxylase to prevent over-production.
What effect on 1-alpha-hydroxylase does FGF23 have?
It inhibits the action. It is released by osteoblasts and osteoclasts in response to PTH.
What is calcitonin and where is it secreted?
- polypeptide secreted by parafollicular cells (C cells) in thyroid gland
What is a communuted fracture?
Bone has broken into many pieces
What is a green-stick fracture?
One side bends and the other side breaks
Describe the first stage of Bone Remodelling
Activation: activation of bone lining cells. The mechanical stress causes them to secret IGF-1.
Describe the second stage of Bone Remodelling
Bone Resorption: osteoclast migrate and become activated. There is MMP activity. Osteoclasts maintain contact though riffled border and integrin. Osteoclasts secrete lysosomes form ecm digestion and HCL for mineral digestion. They release contents into blood.
Describe the Third stage of Bone Remodelling
Reversal: Osteoclasts detach. Osteoprogenitor cells are recruited and they differentiate. There is the formation of the cement line.
Describe the fourth stage of Bone Remodelling
Formation: Osteoblasts form osteoid. This is hydroxyapatite.
Describe the five stage of Bone Remodelling
Osteoblasts become trapped and form osteocytes
What is the function of carbonic anhydrase?
This is found in bone and it catalyses the formation of carbon acid which is a supply of Hydrogen ions.
What is function of RANKL?
This is secreted by osteoblasts and binds to the receptor on osteoclasts precursors.
Give three factors that inhibit osteoclasts activation
- OPG
- Calcitonin
- Oestrogen
- Transforming Beta-GF
- IL-10
Where is GH secreted and what is its function?
It is secreted from somatropic cells in the pituitary gland. Its secretion is enhanced by oestrogen. IGFs are synthesized by GH direct response and this stimulates bone formation.
Give the composition of Bone
Bone is 65% organic which consists on hydroxyapatite.
35% is inorganic and this is 25-30% collagen (mainly type one) and 5-7% non-collagenous proteins (osteocaclin, Osteonectin, Osteopontin)
Give the function of the bone protein Osteocaclin
Bonds hydroxyapatite to collagen
Give the function of the bone protein Osteonectin
Hydroxyapatite crystallization
Give the function of the bone protein Osteopontin
Anchors osteoclasts
Describe the pathway of the nutrient artery
The nutrient artery pieces the diaphysis at the nutrient foramen into the medullary canal. It branches into ascending and descending branches. They will anastomoses with metaphyseal and epiphyseal arteries.
What is the functional unit of Compact Bone?
The functional unit are osteons. This forms the Haversain system. Osteons have a central canal and are surrounded by lamellae. There are spaces called lacunae and they are connected by canaliculi.
What are the properties of principle tensile trabeculae?
Horizontal and for strength