Bone Ossification Flashcards
What are osteoclasts and what is their role?
macrophage derived cells
multinucleated large cells
for resorption of bone to remove old/damaged bone for it to be renewed
monitor bone and decide if it needs to be removed or not
What are osteoblasts?
bone formers and become embedded in bone matrix to become osteocytes
What are the 2 main types of bone in the body?
lamellar and woven
What type of bone is the majority of bone made up of in the body?
Lamellar
What are the 2 types of lamellar bone?
Cortical and trabecular/cancellous
What % of bone is cortical vs. trabecular?
Cortical - Approx 80% of adult skeleton
Cancellous / trabecular bone - Approx 20% of adult skeleton
What is
Woven
Immature
Healing
Pathological
What is the structure of lamellar bone?
Organised, layers
What is an osteon? What is its role?
circular structure unit formed by lamellar bone
runs down outside of bone as columns
allows it to be compressible and strong through rigid coating
What is the structure of the inside of bone? What is its role?
Inside bone is cancellous bone/spongy/trabecular,
still lamellar,
forms inner honeycomb region in diaphysis
gives skeleton bendability/tensile strength rather than compressive as don’t want bone to be too brittle
What are the two types of bone marrow?
Red and yellow (fatty)
Where is red bone marrow found?
Between bone columns/bars/struts
Where is yellow bone marrow found?
in the centre of bone
What is the role of yellow bone marrow?
Makes the bone lighter so less heavy to move
What is the structure of woven bone?
haphazard formation
What is the role of woven bone?
Immature bone used for bone healing and is pathological (joins 2 sides of a fracture together)
How much woven bone should you have in your body?
Not more than 1% in adults
Who may have more woven bone?
Children
Post injury
What is the hole in the middle of an osteon?
Haversian canal (blood vessel)
What do osteoblasts produce?
ECM
What % of the bone ECM is organic and what % is inorganic?
organic 35-40%
inorganic 60%
What are the organic components of the bone ECM?
28% collagen
5% Proteoglycans/ glycoproteins
What is the collagen in the bone ECM for? What type?
Type 1, tensile strength
What are the proteoglycans and glycoproteins for in the bone ECM?
Compressive strength and calcium binding
What are the inorganic components of the ECM?
95% Calcium hydroxyapatite (Ca10(PO4)6(OH)2)
Approximately 5% water
What is the role of Calcium hydroxyapatite?
Coat collagen in ECM on blocks (not continuously) giving it more bendability
What are osteoprogenitor cells derived from?
Mesenchymal cells
What is the role of osteoprogenitor cells?
Live in outer coating of cells and differentiate into osteoblasts when new bone is needed
How do osteoblasts become osteocytes?
Become encased in ECM
What is the role of osteocytes?
Maintain new bone, look after it, ensure high quality, monitor, produce osteoclasts
What are osteoclasts produced by?
Hematopoietic stem cells which are derived by mesenchymal cells
When does ossification begin?
Begins 6th or 7th week of intrauterine life
What are the 2 mechanisms of ossification?
Intramembranous
Endochondral
What does intramembranous ossification usually occur?
Skull
Where does endochondral ossification occur?
Majority of places, mainly everywhere
What is the main difference between intramembranous and endochondral ossification?
Intramembranous ossification is one step forming bone directly whilst endochondral forms cartilage precursor which is then converted to bone
What is first formed in intramembranous and endochondral ossification?
Intramembranous - mesenchymal cells produce osteoblasts
Endochondral - mesenchymal cells produce chondroblasts
What ossification type occurs in the mandible?
Both - mixed intramembranous and endochondral
How does intramembranous ossification occur?
mesenchyme to osteoprogenitor, osteoblasts
Mesenchymal cells condense and differentiate into osteoprogenitor cells which then then differentiate into osteoblasts, these secrete GAGs and bone matrix to become osteocytes as the matrix becomes calcified, on outside get more osteoblasts to more bone growth
What do the mesenchymal cells on the outside do?
On outside, mesenchymal cells condense and form periosteum
What is the role of the periosteum?
Fibrous casing on outside of bone holding the osteoprogenitor cells in place
What bone is first formed in intramembranous ossification and how does this develop?
First woven bone produced as quick which then remodels into adult compact and trabecular bone through blood vessels entering providing the bone with nutrients and osteoclasts
How do sutures from?
Bone spicules grow out from centres of ossification and form sutures, at the same time surface blood vessels grow in
How does endochondral ossification occur?
Mesenchymal cells condense where future bone will form and differentiate into chondroblasts to produce ECM and hyaline cartilage
What collagen is in the ECM of cartilage?
Collagen type 2
How is the ECM in cartilage different to bone?
collagen type 2
higher water content
more GAGs
Do you have periosteum in cartilage?
No, the mesenchymal cells form perichondrium around the outside and hold the mesenchymal cells next to condensing bone forming template for bone formation
What type of growth is there in endochondral ossification?
Interstitial growth - growth in length
Appositional growth - thickness/width
Why is there chondrocyte hypertrophy?
cartilage centre gets further and further from perichondrium nutrient source and diffusion only works for up to 4mm so beyond this the chondrocytes deteriorate as won’t get blood supply
increase in size and get big
What results from chondrocyte hypertrophy?
Center with cavity with holes where chondrocytes once were
What is released by hypertrophied chondrocytes?
cell content which triggers calcification
trigger pH change and release vesicle with alkaline phosphatase in them encouraging calcification of cartilage becoming a hybrid between bone and cartilage
What takes up residence in holy cavity formed from dead chondrocytes?
Nutrient arteries penetrate the perichondrium via nutrient foramen and grow into the cavity brining in osteoclasts from haemopoetic cells from the liver and mesenchymal cells from perichondrium, osteoblasts form from mesenchymal area as calcified
How is the bone collar formed?
On outside perichondrium changes to periosteum forming bone collar
What is formed when the osteoclasts enter the cavity?
Primary ossification centre of woven bone which osteoclasts remove and gets filled with red bone marrow in remodelling to form lamellar bone
What happens at the epiphysis?
Blood vessels grow into them around birth and a secondary ossification centre forms
What happens at the epiphyses?
Hyaline cartilage remains between the diaphysis and epiphysis forming epiphyseal growth plate whilst articular cartilage is at the end of the epiphysis
What are the 4 zones in the epiphyseal growth plate?
Zone of resting cartilage
Zone of proliferating cartilage
Zone of hypertrophic cartilage
Zone of calcified cartilage (cell death)
When does the epiphyseal growth plate become inactive?
18-25 years old when ossification occurs
clavicle is 23-25
What is appositional growth?
Producing new bone on the outside
How does appositional growth occur?
Arteries on outside and periosteum produce osteons (differentiates as osteoblasts and ECM) and blood vessels on outside form ridges getting bigger forming tunnel with vessel in centre
In the tunnel the periosteum becomes endosteum, osteoblasts make new lamellar bone which fills the tunnel and is added to the outside
What is the purpose of appositional growth?
To maintain the thickness of cortical bone
What are the 2 reasons for bone remodelling?
1 - renews bone before deterioration
2- redistributes matrix along lines of mechanical stress
Which bone remodels faster? What does this mean?
Trabecular bone 3-10 times quicker than cortical as larger surface area so can respond to stresses on bone quicker
How long does remodelling last?
160-200 days
What signals remodelling to occur?
Osteocytes have cellular processes which extend in canaliculi and touch their neighbours and act as stress monitors. They are surrounded by blood plasma affected by hormones in blood or molecules we ingest.
When is scletositin secreted?
If osteocytes are healthy they will produce scletositin and inhibit bone formation but if damaged they will secrete it and trigger bone formation
How does bone remodelling occur?
osteoclasts move in and attach to bone forming leak proof seal, releases protein digesting enzymes and HCl via vesicles which digest collagen and dissolve bone minerals, bone proteins and minerals cross the osteoclast to exit into the interstitial fluid,
osteoblasts fill space (lacuna) with osteitis which gets mineralised after 7-10 days for new osteoid to be mineralised
What is your main store of calcium?
bone - 99.9%
what is conc of serum calcium
2.2-2.6 mmol/L
What stimulates PTH
low plasma calcium stimulates parathyroid hormone produced by parathyroid glands to replace serum calcium level
What PTH promote?
- calcium realise option from kid
What does PTH promote initially?
- Ca2+ reabsorption from kidney and PO4 excretion
- initiates synthesis of vitamin D in kidney
- ## vitamin D increases calcium absorption from gut
What if the kidneys and gut can’t increase calcium conc. levels enough?
Calcium reabsorption from bone is increased but this is a longer process
osteoclast number and activity is increased
osteoblasts have PTH receptor so still due to PTH
expression of RANKL (ligand for receptor RANK which osteoclast precursors have)
RANKL causes osteoclast proliferation and differentiation
What happens when calcium levels return to normal?
Calcitonin is released from C-cells in thyroid gland which inhibits osteoclast resorption and reduces calcium in the kidney
What is the effect of oestrogen on calcium? What does this mean?
Increases calcium absorption in the gut
Decreases re-absorption in the bone inhibiting osteoclasts
So in menopause you get loss of bone mass and osteoporosis
What is the effect of glucocorticoids on calcium? What does this mean?
Causes gut to decrease calcium absorption,
bone increased re-absorption so decreased formation - - prolonged corticosteroid treatment could cause osteoporosis
