26- Bone and bone healing Flashcards
What are the 2 layers of bone?
- outer dense cortical bone
2. inner spongey trabecular bone
what are the 2 major cells in bone?
- osteoblasts
- osteoclasts
What do osteoclasts do?
Catabolise bone for mineral regulation and bone remodelling
What do osteoblasts do?
BUILD BONE
make and mineralise osteoid
become osteocytes
What are the 2 major constituents of bone?
- Matrix
2. Cells
What does the matrix in bone contain?
- type 1 collagen and other proteins
- calcium hydroxyapatite
What is calcium homeostasis maintained by?
The balance of:
- net dietary intake
- urinary excretion
How much calcium is absorbed in the gut?
about 1/5, net intake is 200mg from 1g
Once calcium enters the blood where does it go?
Either it is stored in bones or it is filtered in the kidneys
What is the calcium in bones used for?
1- to repair bone
2- as a reservoir/storage when ca2 needed for signals
How much calcium is filtered/excreted out?
Same amount as is absorbed in order to balance homeostasis by the endocrine system
What controls calcium homeostasis?
The parathyroid gland
When there isn’t enough calcium what does the parathyroid gland do?
- More calcium is absorbed in the gut
- Calcium stores from bone released
- Less calcium excreted from the kidney
What system co-ordinates the endocrine response?
The endocrine response
What are the 2 measurements of plasma calcium levels
- Total plasma calcium levels
2. Free ionised calcium concentration
What is the normal plasma calcium level?
2.5mM
What is the free ionised calcium concentration?
1.2mM (approx 45% of normal calcium plasma)
Where is 35-40% of calcium in the blood bound to?
Macromolecular proteins such as albumin
How many parathyroid glands do we have?
4
Where is parathyroid hormone produced?
In chief cells in the parathyroid gland
What is the parathyroid gland derived from?
the pharyngeal pouch endoderm driven by a gene called gcm-2
What kind of hormone is PTH
A peptide hormone
How many amino acids is PTH?
84
What is the half-life of PTH?
20 minutes
Where is PTH cleaved?
In the liver
What is parathyroid hormone secretion inversely proportional to?
Serum calcium levels
What is the main target of PTH?
- Kidney
- Bone
For healthy bones what type of PTH secretion would you like?
Pulsatile
What will release of PTH do?
Raise calcium levels in the blood
How does PTH elevate plasma calcium levels?
- increased bone resorption
- Increased calcium renal absorption by decreasing excretion
- Stimulate production of active form of vitamin D3
What are the conflicting effects of PTH?
- PTH tends to cause bone resorption via the RANKL OPG RANK system
- Pulsatile PTH can increase bone formation by enhancing osteoblastogenesis or osteoblast survival
- PTH induced bone formation is mediated in part by a drop in SOST/Sclerostin expression in osteocytes
What is a type 1 PTH receptor?
A G coupled receptor (ClassB)
highly expressed in the bone and the kidney
What level do we want to keep ionized calcium to?
1.2mM
What happens when parathyroid cell releases PTH?
- increases plasma calcium
- increases Calcitriol
What is PTH release regulated/suppressed by?
- CaR (calcium receptor) - suppresses PTH release
- VDR (vitamin D receptor) - suppresses transcription/generation of PTH
What is primary hyperparathyroidism
Too much PTH released caused by a monoclonal parathyroid adenoma
What does primary hyperparathyroidism cause?
- increased PTH secretion
- leads to hypercalcemia (high ca2 levels in blood)
- hypophosphataemia (low phosphate)
- bone demineralisation
- hypercalciuria
- multiple bone cysts (osteitis fibrosa cytica)
What type of hormone is Vitamin D?
Steroid hormone
What is vitamin D also known as?
Calcitriol, 1,25(OH)2 Dihydroxycholecalciforol
What does vitamin d start as?
Cholesterol
Brief course of vitamin d3?
- cholesterol converted to provitamin d3 in the intestine
- then converted to previtamin d3 in the skin
- then converted to vitamin d3
- then converted to 25(OH)D3 in the liver by addition of hydroxyl group
- then converted to 1,25(OH)2D3 calcitriol in the kidney
What is vitamin d synthesis controlled by?
Parathyroid hormone
When provitmain d3 is exposed to what is it converted to previtamin D3?
UVB
What are the effects of calcitriol?
- increases net intestinal uptake of ca2+ from 200 to 600mg/day
- increases calcium serum levels by increasing bone resorption and increasing renal ca reabsorption
- becomes lipid soluble by binding to it D binding protein
What can chronic vitamin D deficiency lead to?
Secondary hyperparathyroidism
osteomalacia
How much calcium is reabsorbed in the distal convoluted tubercle?
9%
What acts on the DCT stimulating the reabsorption process of calcium?
Vitamin D
What 2 proteins help calcium cross the apical membrane of kidneys.
TRPV5
TRPV6
What are the pros of sunlight?
Sunlight makes vitamin D which reduces bone disease and muscle weakness and helps reduce cancers of the colon, prostate and breast
What are the cons of sunlight?
Ages skin
Increases risk of skin cancer by damaging the DNA, increases risk of melanoma
What type of hormone is calcitonin?
A peptide hormone
How many amino acids is calcitonin?
32 amino acids
What produces calcitonin?
Parafollicular thyroidal c cells
What does calcitonin do?
Decrease plasma Ca2+ following a calcium load, by decreasing osteoclast activity, decreasing bone resorption therefore allowing rapid bone deposition
What is secretion of calcitonin inhibited by?
Low calcium levels in the blood
Name some diseases that can be caused by a failure of calcium homeostasis?
- primary hyperparathyroidism
- secondary hyperparathyroidism
- osteoporosis
- rickets
- calcium stones
- receptor mutations
What is rickets?
A vitamin D deficiency due to inadequate intake of provit or sun exposure
What is osteoporosis?
having a bone mineral density of 2.5 standard deviations below healthy controls
What is osteopenia?
having a bone mineral density of 2.5 standard deviations above healthy controls
How is osteoporosis diagnosed?
By a DXA (dual-energy X-ray absorptiometry)
What does osteoporotic bone loss lead to?
An imbalance in bone remodelling, i.e too much break down, not enough bone formation to balance it.
What can osteoporotic bone loss cause?
microfractures where filaments become so thin they fracture and don’t connect. this means small injury could shatter this weak bone (deterioration of micro-architecture of the bone)
What is adult bone health determined by?
- peak bone mass (pbm)
- the rate of bone loss with age
What does oestrogen bind to?
Osteoblastic oestrogen receptors ERalpha and ERbeta
What medications are given to prevent bone fractures in postmenopausal women with osteoporosis
- alendrate
- etidronate
- risedronate
- stronium
- ranelate
- raloxifene
How do biphosphonates help the treatment of postmenopausal osteoporosis
they coat the bone making it resistant to osteoclasts
For women who have already suffered a fracture what additional drug is prescribed?
Teriparatide
What are the main phases of bone fracture repair?
- Reactive phase- formation of granulation tissue
- Reparative phase 1 - replacement of granulation tissue with callus
- Reparative phase 2- replacement of callus with lamellar bone
- Remodelling of bone to normal contour
What is the first thing that happens when you have a bone fracture?
A haematoma is formed, granulation tissue is formed, later a primary callus is formed. Dead bone is resorbed and immature woven bone appears. Then this woven bone (callus) is gradually replaced with lamella bone. eventually, callus goes, bone matures and is remodelled to normal contour.
What happens post tooth extraction?
Socket filled with clot
why do macrophages infiltrate the tooth socket?
to fight infections
Why do fibroblasts infiltrate the tooth socket?
to begin to make collagen structure
Why do osteoblasts infiltrate the tooth socket?
To make minerals
