Normal Bone Function Flashcards
Purpose of the skeleton
Raises us from the ground against gravity
Determines basic body shape
Transmits body weight
Forms jointed lever system for movement
Protects vital structures from damage
Houses bone marrow
Mineral storage- calcium, phosphorus, magnesium
Which minerals are stored in bone
Calcium
Phosphorus
Magnesium
Number of bones in appendicular skeleton
126
Number of bones in axial skeleton
80
What is the skeleton divided into
Axial
Appendicular
Bone classification by shape
Long bones
Short bones
Flat bones
Irregular bones
Sesamoid bones
Long bones
Tubular shape with hollow shaft and ends expanded for articulation with other bones
Short bones
Cuboidal in shape
Flat bones
Plates of bones
Often curved
Protective function
Sesamoid bones
Round, oval nodules in a tendon
Irregular bones
Various shapes
Types of bone structure- macro
Cortical
Trabecular
Cortical bone structure
Compact
Dense, solid, only spaces are for cells and blood vessels
Trabecular bone structure
Cancellous
Spongy
Network of bony struts (trabeculae) , looks like sponge, many holes filled with bone marrow
Cells reside in trabeculae and blood vessels in holes
Types of bone structure- micro
Woven
Lamellar
Woven bone
Made quickly
Disorganised
No clear structure
Lamellar bone
Made slowly
Organised
Layered structure
Function of hollow long bone
Keeps mass away from neutral axis
Minimises deformation
Function of trabecular bone
Gives structural support while minimising mass
Number of baby bones in body
350
Number of adult bones in body
206
Wide ends of bone function
Spreads load over weak, low friction surface
Flat bones function
Protective
Bone composition
50-70% mineral
20-40% organic matrix
5-10% water
Bone composition- mineral
Hydroxyapatite
A crystalline form of calcium phosphate
Hydroxyapatite
A crystalline form of calcium phosphate
Bone composition - organic matrix
Collagen type 1- 90% of all protein
Non-collagenous protein - 10%
What type of collagen composes bone
Type 1
How does collagen assemble in bone
Assembles in fibrils with mineral crystals situated in ‘gap’ regions between them
Function of mineral in bone
Stiffness
Structure of collagen in bone
Elasticity
Cells of bone
Osteoclasts
Osteoblasts
Osteocytes
Bone lining cell
Osteoclasts structure
Mutlinucleated
Osteoblasts shape
Plump
Cuboidal
Osteocyte shape
Stellate
Entombed in bone
Bone lining cell shale
Flattened
Lining the bone
Origins of osteoblasts
Mesenchymal stem cell
Function of osteoblasts
Form bone- in form of osteoid
Produce type 1 collagen and mineralise the extracellular matrix by depositing hydroxyapatite crystal within collagen fibrils
High alkaline phosphatase activity
Make non-collagenous proteins
Secreted factors that regulate osteoclasts - RANKL
Origins of osteoclasts
Haematopoietic stem cells
Function of osteoclasts
Resorb bone
Dissolved the mineralised matrix (acid)
Breakdown the collagen in bone (enzymatic)
High expression of TRAP and cathepsin K
How is the mineralised matrix dissolved
Acid
How is the collagen in bone broken down
Enxymes
Bone modelling
Gross shape is altered
Bone added or taken away
Bone remodelling
All of the bone is altered, new bone replaces old bone
Bone remodelling
Resting phase
Activation
Resorption
Reversal phase
Formation
Age of bone development -modelling
0-20
Age of bone maintenance- remodelling
20-50
Age of bone osteoporosis- acquired pathology
50+
Reasons for bone remodelling
Form bone shape
Replace woven bone with lamellar bone
Repair damage
Obtain calcium
Response to loading (exercise)
Reorientate fibrils and trabeculae in favourable direction for mechanical strength
Long bone examples
Humerus
Femur
Where are Sesamoid bones found
Hand
Feet
Knee cap
What can mesenchymal stem cells become
Adipocytes
Osteoblasts
Chondrocytes
Fibroblasts
Myoblasts
What factors regulate osteoclasts
RANKL
What do osteoclasts have a high expression of
TRAP
Cathepsin K
How often do you fully replace your skeleton
Every 10 years
Which hormone controls osteoclasts —-> leading to osteoporosis
Oestrogen
What type of bone is the skull
Flat
What type of bone is vertebrae
Irregular
Where would you predominantly find trabecular bone
Metaphysis of long bone
Irregular bones
Where would you predominantly find trabecular bone
Metaphysis of long bone
Irregular bones
Building a collagen fibres
Tropocollagen
Collagen fibrils
Collagen fibres
Amino acid sequence of collagen molecule
Glycine - X - Y
Up to about 1000 amino acids
X and U are often proline, hydroxyproline or hydroxylysine
Allows formation of alpha helix
What is a biomarker of collagen synthesis
P1NP
P1CP
Which amino acid is the 3rd amino acid in a collagen molecule
Glycine
What forms the tropocollagen molecule
3 collagen chains
2 alpha-1
One alpha-2
Number of residues per turn of collagen
3
What holds the tropocollagen molecules and fibril together
Covalent crosslinks derived from lysine/hydroxylysine side-chains
Processing of type 1 collagen
N-terminal propeptide and C-terminal propeptide cleaved to create correct length of collagen
Structure of collagen
Triple helic
Covalent cross-links within and between tropocollagen
-OH-lysine x2
Lysyl oxidase
What does lysyl oxidase require
Copper
Biomarkers of type 1 collagen breakdown
NTX
CTX
Hydrogen bonds within tropocollagen
Between hydroxyproline molecules
OH-proline from proline requires Fe2+
What does the conversion of Fe3+ to Fe2+ require
Vitamin C
Cross-links between tropocollagen
OH-lysine x3 = pyridinolines
Which enzymes break down collagen
Proteinases especially collagenases and cathepsin K
Type 1 collagen
Bone, tendon, ligaments , skin
Type 2 collagen
Articular cartilage
Vitreoud
Type 3 collagen
Wound healing
Type 4 collagen
Basal lamina
Type 5 collagen
Cell surfaces
Type 10 collagen
Growth plate
What synthesises the bone matrix
Osteoblasts
Other proteins found in bone matrix
Osteocalcin
Osteonectin
Osteopontin
Fibronectin
Bone sialoprotein
Bone morphogenetic proteins
Function of other proteins in bone matrix
Contribute to structure
Regulate bone cell activity
Bone mineralisation
Alkaline phosphatase hydrolyses pyrophosphate
Inorganic phosphate complexes with calcium to form hydroxyapatite
Hydroxyapatite crystals propagate along colagen
What stimulates growth plate fusion
Oestrogen
Which bones are formed by intramembranous ossification
Skull
Clavicles
Which bones are formed by endochondral ossification
Long bones
Appositional growth
Growth of bone diameter
Osteoblasts deposit bone
Osteoclasts resorb bone in the centre
How many tropocollagen molecules pleat together
5
Examples of short bones
Carpals
Tarsals
At what age is peak bone mass reached
25
Which enzyme is needed for bone mineralisation
Alkaline phosphatase
Function of collagen in bone
Allows deformation (toughness)
Creates structure for hydroxyapatite
What is common to all collagens
Triple helix
Function of osteocytes
Maintain mineral concentration of matrix
Woven bone
woven bone (primary) - appears in embryonic development and fracture repair. Consists of osteoid with the collagen fibres arranged randomly
Lamellar bone
Lamellar bone (secondary) - bone of the adult skeleton. Consists of highly organised sheets of mineralised osteoid making it much stronger. It can be further subdivided into 2 types:
1. Compact bone - lamellae are organised into concentric circles which surround a vertical Haversian canal (which transmits small Neurovascular and lymphatic vessels) = osteon. Osteocytes are located between the lamellae within lacunae , and the lacunae are interconnected by canaliculi
2. Spongy bone - contains many large spaces. The bony matrix consists of a 3D network of fine columns which cross link to form irregular trabeculae- producing a light porous bone. The spaces between trabeculae are filled with bone marrow.
Osteocytes
as the osteoid mineralises, osteoblasts become entombed between lamellae in lacunae where they mature into osteocytes which monitor the minerals and proteins to regulate bone mass
Organic components of bone
include mainly type 1 collagen (providing tensile strength and elasticity); proteoglycans (responsible for compressive strength); matrix proteins, including osteocalcin, osteonectin and osteopontin (which promote mineralisation and bone formation); cytokines and growth factors.
Inorganic components of bone
include calcium hydroxyapatite (providing compressive strength)and osteocalcium phosphate.
Percentage of organic and inorganic components of bone
40% organic
60% inorganic
Joe, a 7 year old male, comes into clinic with unexplained muscle pain and weakness. He presents with signs of scurvy - a vitamin C deficiency disease. Fe(III) is converted to Fe(II) by vitamin C and is crucial in the hydroxylation step of collagen synthesis in muscles. What is the molecule that forms hydrogen bonds within tropocollagen?
Hydroxyproline
Srinath the world’s best badminton player goes to his physiotherapist with pain in what he thinks is his ligaments. However, the physiotherapist says the pain is more likely to come from tendons and she tries to explain to Srinath why this is. Which one of these is not a property of tendons?
High elastin content
Strain variables
Rate
Magnitude
Frequency
Dwell (hold/rest periods)
Number of cycles
What is bone formation response affected by
Sex
Age
Hormone
Cytokines
Drugs/medicines.nutraceuticals
The mechanostat theory
There is not a single mechanostat
Our skeletons contain vast number of small units of bone, each of which has its own dynamically regulated mechanostat
Maximising response to loading
Bone responds maximally to only a few loading cycles each day
Exercise in the previous 4 hours increases the response to subsequent loading
Bone responds to very brief mechanical events
Rest periods between single loading events (-10 s) increase their effect
Which cells sense loading
Osteocytes
How do osteocytes sense loading
Fluid flow shear stress
Loading
Increases bone formation
Off-loading
Decreases bone formation
What happens to bone when they are loaded
Deformation and strain
Strain
Change in length/ length
Deformation
Force causes deformation- change in length
How do osteocytes sense mechanical strain
detecting fluid shear around their dendrites in canaliculae
How do osteocytes manage the activity of osteoblasts and osteoclasts
partly through direct contact with dendrites to cells on the bone surface
partly by secretion of signalling proteins such as RANKL, OPG sclerostin (there are now drug treatments for osteoporosis based on OPG and sclerostin).
Osteocytes also secrete FGF-23 which regulates phosphate excretion.
Which of these are dietary sources of phosphate?
meat, dairy, soy, seeds and nuts. Carbonated soft drinks can also have high phosphate content.
Which component of bone confers the mechanical property of stiffness?
Mineral
Which hormone is the main regulator of serum calcium concentration?
Parathyroid hormone
Which is a physiological function of synovial fluid?
Reduce friction of joint movement
Which of the following is a source of uric acid?
Adenine