The Cellular Structure Of Bone Flashcards
What are the functions of bone?
Structure, mechanical, protective, metabolic
What is the structural function of bone?
Give structure and shape to the body
What is the mechanical function of bone?
Sites for muscle attachment
What is the protective function of bone?
Vital organs and bone marrow
What is the metabolic function of bone?
Reserve of calcium and other minerals
What are the proportions of inorganic and organic bone?
65% inorganic, 35% organic
What makes up the inorganic part of bone?
Phosphorus, sodium, magnesium, calcium hydroxide
What makes up the organic part of bone?
Bone cells and protein matrix
What are the types of anatomical bones?
Flat, long, short, irregular and sesamoid
What are examples of flat bone?
Sternum/ skull
What is the function of flat bone?
Protective
What is the distinguishing structure of long bones?
Longer than they are wide
What is the function of long bone?
Allow us to make big movements
What are some examples of short bones?
Carpals in hands or tarsals in feet
What is the function of short bone?
Provide stability in joints and allow us to make smaller movements
What is the distinguishing feature of short bone?
As long as they are wide
What is the function of irregular bones?
Complex shapes that protect specific organs like the pelvis or vertebrae
What are sesamoid bones?
Embedded in muscle or tendons and act like a pulley to reduce stress
What are the two macroscopic types of bone?
Trabecular and cortical
What are the features of trabecular bone?
Thin, honeycomb-like Highly metabolic Adds strength 15-25% calcified Large SA
How much of the skeleton is made up of trabecular bone?
20%
Which bit of the bone is made up of trabecular bone?
The axial bits (Epiphysial)
What are the features of cortical bone?
Thick bone that makes up the shaft of the bone
80-90% calcified
What are the functions of cortical bone?
Mainly structural, mechanical and protective
Which bit of the bone is made up of cortical bone?
Shaft
How much of the Skeleton is made up of cortical bone?
80%
What are the two types of microscopic bone structure?
Woven and lamellar
When is woven bone usually around?
During initial bone development
Is woven bone mature or immature?
Immature
Is lamellar bone mature or immature?
Mature
In what type of bone does endochondral ossification happen in?
Long bones
In what type of bone does intramembranous ossification happen in?
Flat bones
What is intramembranous ossification?
Direct differentiation of osteoblasts from connective tissue
What is endochondral ossification?
Bones forming from a cartilage model
What bones fuse together last (and at what age)?
Clavicle growth plates at 20 yrs
How does endochondral ossification work?
Cartilage model is made in the womb.
Blood vessels invade the scaffold, bringing precursors for bone cells
Precursors differentiate into bone (called primary ossification centre)
First occurs in the diaphysis and moves towards the epiphysis
Secondary ossification centre formed in the epiphysis
When is bone growth complete?
When the primary and secondary ossification centres fuse together
What do growth plates allow for?
Rapid linear growth
What are growth plates made of?
Cartilage which contains chondrocytes organised into a structure with three distinct layers
What are the three layers of growth plates called?
Reserve zone, proliferative zone and hypertrophic zone
What does the reserve zone contain?
Stem cells
What happens in the reserve zone?
Stem cells proliferate very slowly to maintain their population
How close is the reserve zone to the blood supply?
Very
What happens in the proliferative zone?
Chondrocytes become highly proliferative and form distinct column-like structures. As more get made, they move further away from the blood supply, causing hypertrophic differentiation
What happens in the hypertrophic zone?
Chondrocytes undergo apoptosis, leaving behind a mineral matrix which then calcifies and is ossified by bone cells
Do cells move in the growth plate?
No
What are the three types of bone cells?
Osteocytes, osteoclasts and osteoblasts
Which are the mature bones cells?
Osteocytes
Which are the immature bone cells?
Osteoblasts
What do osteoblasts do?
Produces osteoid to form new bone
What do osteoclasts do?
Secrete acids and enzymes that resorb/remove bone
How are osteoclasts formed?
Fusion of macrophages
How do osteoclasts work?
Sealing off a portion of bone beneath them by forming an actin ring
What are osteocytes?
Mechanosensory network embedded in the lacunae of mature bone
How are osteocytes connected?
Processes through cannilicular channels
What are the three overall steps in bone remodelling?
Microfracture
Resorption
Formation
What is a microfracture?
Tiny cracks forming in bone from stresses and strains in older bone tissues
What detects microfractures?
Osteocyte mechanosensory network
What happens when the Osteocyte mechanosensory network senses a microfracture?
Signals to the osteoclast to come in and resorb the old, damaged bone
What happens in the resorption step in the bone remodelling cycle?
Osteoclasts differentiate at the microfracture and resorb away the old bone and then dedifferentiate into individual mononuclear cells
What happens in the formation step of bone remodelling?
Osteoblasts secrete osteoid to repair the resorbed bone
When does bone disease happen?
Either when the formation doesn’t return the bone to its original width or when there is excess formation
What would cause the formation to not return the bone to its original width?
Excess resorption or not enough formation
What would cause excess bone formation?
Either due to insufficient resorption or excess formation
What is it called when bone formation doesnt return to its original width?
Bone loss or osteoporosis
What’s it called when there is excess bone formation?
Bone gain or osteosclerosis
What are the endocrine controls of bone remodelling?
Estrogen, thyroid hormone, PTH
What are the paracrine controls of bone remodelling?
RANKL, Wnt signalling
What is RANK receptor activation required for?
Osteoclast differentiation and survival
What is RANK ligand produced by?
Osteocytes and osteoblasts
How does RANK ligand work?
Binds to RANK receptor causing the signalling cascade resulting in the fusion, differentiation and activation of the osteoclast
What does OPG stand for?
Osteoprotegerin
What is OPG?
Decoy receptor for RANKL also produced by osteocytes and osteoblasts
What is an example of a synthetic OPG?
Denosumab
What does denosumab work to do?
Prevent bone loss by osteoclasts
What does wnt signalling stimulate?
Osteoblast differentiation
What does wnt signalling inhibit?
Sclerostin and DKK-1
How does wnt signalling work?
Wnt binds to the frizzled receptor and sets off a signalling cascade that results in the translocation of beta Katenin causing a change in gene expression and leading to osteoblast differentiation
What does the frizzle cell membrane receptor have to be bound to for it to work?
LRP 5 and 6
What do osteocytes secrete?
OPG and sclerostin
What is osteopetrosis?
Excess bone formation
What are the two situations systemic osteopetrosis could occur in?
LRP5 activating mutations: Van Buchems and SOST
What is the non-systemic reason osteopetrosis would occur?
Locally at the site of prostate metastasis
What is van buchems?
No production of sclerosis by the osteocytes so excess osteoblast differentiation
What are the characteristics of van buchems?
Enlarged mandible, skull and generalised bone overgrowth
What are the symptoms of van buchems?
Nerve palsies and headaches because of the increased intercranial pressure
What is the definition of osteoporosis?
Bone mass < 2.5 standard deviations below average peak bone mass
How many people does osteoporosis affect?
1:2 women and 1:5 men
What is primary osteoporosis caused by?
Menopause or aging
What is secondary osteoporosis caused by?
Drugs, disease or lifestyle
How does the menopause cause osteoporosis?
Loss of Estrogen causes a temporary increase in osteoclast activity causing a sudden loss of bone mass that lasts until the body gets used to the new oestrogen levels