Phase 2 - Week 1 (Bones, Osteoporosis, Fractures) Flashcards
Diaphysis
Central shaft of a long bone
Epiphysis
Regions at either end of a long bone
Epiphyseal Plate
Between diaphysis + epiphysis (also called growth plate)
Metaphysis
Area adjacent to epiphyseal plate, part of bone where growth occurs
Describe how bones grow
- During growth, the metaphysis is made of cartilage - more cartilage is produced to increase length of bone
- After puberty (by age 21) - epiphyseal plate becomes fully mineralised, becomes the epiphyseal line
- Growth in length = deposition of new cartilage at metaphysis and subsequent mineralisation/calcification of cartilage into new bone material
Periosteum
Covers surface of bones, consists of an outer layer of tough fibrous tissue and an inner layer of osteogenic tissue (bone-forming tissue consisting of osteoblast cells)
List the types of bone marrow and describe their functions
- Yellow Marrow - stores adipose tissue
2. Red Marrow - contains Haematopoietic tissue which produces red blood cells
Where is yellow bone marrow found?
In the medullary cavity - space running through centre of bone. Lined by osteogenic tissue - endosteum.
Where is red bone marrow found?
In the epiphysis of long bones and in small, flat + irregular bones
Describe the components of the bone matrix
Organic and inorganic components
Describe the organic components of bone
Organic = osteoid - produced by osteoblasts, maintained by osteocytes (type 1 collagen + ground substance)
Describe the inorganic components of bone
Inorganic = 50% of bone, hydroxyapatite (inorganic mineral - mineral salts e.g. calcium phosphate, calcium carbonate)
Describe the major blood supply of bones
- Main supply is through the nutrient artery (in long bones enters into shaft)
- Enters bone at nutrient foramen, spreads through bone, supplies trabecular, compact bone etc.
- Periosteal BV (on outside of bone) supplies outside of bone
How are Osteons supplied with blood?
Via their central canals.
Describe the function of Volkmann’s canals
Transfer blood from the periosteum to central canals
Describe the function of canaliculi
Canals which link lacunae, provide routes for nutrients to reach osteocytes/waste products to leave them
List the types of bone tissue
- Compact (dense/cortical)
2. Spongey (trabecular/cancellous)
Describe the structure of Compact bone
- Outer part of all bones
- All of flat bones
- Dense, few spaces - protection + support (reduces stress of weight bearing in long bones)
- Functional units = Haversian systems/Osteons
Osteons
- Contain a central canal with blood vessels, lymphatics + nerves
- Surrounded by concentric rings of lamellae (compact bone tissue) w/ lacunae (spaces) between containing osteocytes
- Canaliculi radiate from lacunae forming branching network
Describe the structure of Spongey bone
- In epiphysis of long bones + pelvis, ribs, vertebrae, skull
- Thin bony plates of spicules of bone called trabeculae, between which are large spaces filled w/ bone marrow
- Compressive + tensile trabeculae
- Trabeculae contain lacunae containing osteocytes - nourished by blood in marrow cavities from BV penetrating spongey bone from periosteum
Compressive Trabeculae
Arranged along line of force (vertically) to carry weight
Tensile Trabeculae
Arranged horizontally for support
List the types of bone cells
- Osteoprogenitor cells
- Osteoblasts
- Osteocytes
- Osteoclasts
Explain maturation of bone cells
Osteoprogenitor cells –> Osteoblasts –> Osteocytes
Mononuclear phagocytic cells –> Osteoclasts
Osteoprogenitor cells
- On surface of bone
- Become activated if there is injury
- Differentiate into osteoblasts
Osteoblasts
- On surface of bone + line internal marrow cavities
- Have many mitochondria + Golgi apparatus for protein synthesis
- Secrete constituents of osteoid (organic matrix of bone) - type 1 collagen, proteoglycans + glycoproteins - important in mineralisation (calcification) of matrix
- Have receptors for parathyroid hormone + calcitriol
Osteocytes
- Mature bone cells derived from osteoblasts
- In lacunae
- Adjacent osteocytes linked by cytoplasmic processes through canaliculi
Osteoclasts
- Large multinucleated cells derived from fusion of several precursor cells - contain many mitochondria/lysosomes - Very mobile
- Responsible for resorption of bone - skeletal remodelling
- Abundant at surfaces undergoing erosion
- At site of contact with bone, microvilli that infiltrate disintegrating bone surface
- Calcium, phosphate + bone matrix constituents released into extracellular fluid
- Activity controlled by hormones - parathyroid hormone, calcitonin, thyroxine, oestrogens + metabolites of Vit. D
Describe the main functions of bone
- Protection/structural support
- Attachment for muscles, tendons, ligaments allowing movement through articulation
- Homeostasis of minerals (calcium + phosphate)
- Haematopoiesis - red bone marrow
- Storage of triglycerides
Describe the functions of calcium in bone
- Calcification of bones gives strength, structural support and rigidity to bones
- Bone acts as a metabolic reservoir of calcium for extracellular homostasis
- Makes up most of inorganic ECM of bone as calcium hydroxyapatite, which gives bone rigidity
Describe why calcium is needed throughout the body
- Muscle contraction
- Nerve excitability
- Intracellular messenger
- Blood coagulation
Describe calcium in serum
- Either free (unbound/unionised), bound to albumin or complexed
- Free calcium is what regulates feedback mechanisms
- 50% of total serum calcium is bound to albumin
How is serum calcium level measured
- Total = bound + free calcium
- Adjusted calcium = total adjusted to normal albumin level
Hypercalcaemia
Serum calcium is too high
Hypocalcaemia
Serum calcium is too low
Normal serum calcium level
2.2-2.6mmol/l
List the organs involved in calcium homeostasis
- Gut - absorption of dietary calcium
- Kidney - filtration + reabsorption of calcium
- Bone - storage of calcium
- Parathyroid glands - secrete PTH
- Liver - helps production of calcitriol
Where does the calcium in the body come from?
All calcium comes from diet (25 mmol/day)
Describe how dietary calcium is absorbed
Absorbed by the gut - mainly duodenum + jejunum
- cell-mediated active transport pathway - controlled by calcitriol
- passive diffusion dependent on luminal calcium concentration
Explain how calcium absorption in the gut is mediated
Proportion of calcium absorbed by active transport depends on calcitriol - can range from 20-60%. Calcitriol increases fractional absorption if dietary intake falls, during growth, pregnancy and lactation.
Where will calcium absorbed from the gut be transported?
It is absorbed into the bloodstream - into plasma.
Describe the role of the kidneys in calcium homeostasis
- Plasma is filtered by the kidneys
- 65% of calcium reabsorbed in PCT (coupled to bulk transport of solutes e.g. Na + water)
- 20% reabsorbed in thick ascending Loop of Henle
- 15% reabsorbed in DCT
- Reabsorption in Loop + DCT increased by effect of PTH
- Remainder excreted in urine
Describe the mechanism of action of Parathyroid Hormone
Acts to vary the amount of calcium reabsorbed in kidneys and absorbed into bones + stimulates formation of calcitriol in kidneys to increase calcium absorption from gut.
Where and why is PTH produced?
Produced in the parathyroid glands in response to low levels of free calcium
How do the Parathyroid glands detect a change in free calcium levels?
Have calcium sensing receptors (G-protein coupled receptors) which sense levels of free calcium - main physiological ligand is calcium.
Describe what happens to the level of PTH when calcium levels:
a) Increase
b) Decrease
a) PTH decreases
b) PTH increases
Small change in calcium produces large change in PTH
Describe the series of events which occur when ionised calcium decreases
PTH -
- stimulates calcium reabsorption in renal tubules
- stimulates formation of calcitriol in kidney, which enhances calcium absorption from gut
- Promotes bone resorption - increase in number + activity of osteoclasts in bones, releasing calcium into blood
- Rise in iCa back to normal
Explain how bone resorption affects calcium homeostasis
Bone resorption by osteoclasts releases calcium into the bloodstream, so if bone resorption is increased (by PTH) calcium level will be increased and if bone resorption is decreased (by calcitonin) calcium level will be decreased.
Describe the series of events which occur when ionised calcium increases
- The parafolicular cells of the Thyroid gland secrete increased levels of Calcitonin
- Calcitonin stimulates an increase in number and activity of osteoblast cells in bone, preventing calcium release into blood
- Calcitonin also decreases the level of calcium reabsorption in the kidneys
- Decrease in ionised calcium levels back to normal
Define Osteoporosis
Clinical condition characterised by compromised bone strength meaning there is an increased risk of fracture
Explain the cause of Osteoporosis
- Imbalance between bone resorption + formation (resorption higher than formation)
- Decrease in oestrogen - increased RANK ligand as less OPG to block it
- Decrease in Oestrogen causes increase in bone resorption so bones become thinner + weaker
- Genetic predisposition
Describe how bone density changes throughout a person’s lifetime
- Bone mineral acquisition occurs mainly during puberty - bones increase in length/diameter/trabecular thickness
- Peak bone density - age 21
- Consolidation of bone density - up to age 40
- Decline in bone density - age 40 onwards, much more dramatic in women (due to oestrogen)
Describe the factors which affect peak bone density
- Lifestyle - smoking, physical activity, alcohol intake
- Nutrition - calcium intake
- Hormones (growth hormones, oestrogen)
- Genetic predisposition
- Gender
What is the affect of a drop in bone density?
Makes bones more susceptible to fractures - common fracture sites = distal radius, vertebrae and pelvis
List the risk factors for osteoporosis
- > 65 years old
- Vertebral compression fracture
- Fragility fracture after age 40
- Family history of osteoporotic fracture (especially maternal hip fracture)
- Malabsorption syndrome
- Primary hyperthyroidism
- Propensity to fall
- Osteopenia
- Early menopause
- Rheumatoid arthritis
- Low dietary calcium intake
- Smoking
- Excessive alcohol/caffeine
- Weight <57kg/significant weight loss at 25 y/o
- Long term heparin therapy
List the complications of bone fractures due to Osteoporosis
- Permanent disability
- Pain
- Deformity
- Physical deconditioning
- Loss of height
- Kyphosis
- Increased mortality
- More likely to fracture again
How is the risk of fractures determined?
Bone strength + extraskeletal conditions (propensity to fall + fall conditions)
Describe how Osteoporosis is diagnosed
Based on T-score.
Define T-Score
Number of standard deviations above/below mean for a healthy adult population of the same sex/ethnicity as the patient
List the T-score range for:
a) Normal
b) Osteopenia
c) Osteoporosis
d) Established Osteoporosis
a) > -1
b) -1 to -2.5
c) < -2.5
d) < -2.5 + presence of one or more fractures
What is the aim of treatment of Osteoporosis?
Reduction in fracture risk/number of fractures occurring
Describe the non-pharmacological treatments for Osteoporosis
- Lifestyle changes - intake of dietary calcium, exercise, stop smoking, drink alcohol safely
- Minimise risk of falls - avoid drugs w/ risk of fall, identify + treat sensory deficits etc.
- Exercise increases bone density
Describe the Pharmacological treatments for Osteoporosis
- Only used if non-pharmacological is ineffective
- ## Calcium + Vitamin D stop fracturesBisphosphonate is most common treatment - leads to bone remodelling - anti-resorptive, increases bone density + strength
- E.g. Alendronate/Alendronic Acid, Zolendronate, Risendronate, Etidronate
- Denosumab - monoclonal antibody, binds RANK ligand and inhibits osteoclast formation, function + survival, no longer have high bone resorption
Define Fracture
Break in continuity of bone
How are fractures classified?
- Completeness of break
- Complete or incomplete fracture - Break orientation
- Transverse or linear - Bone position
- Non-displaced or displaced - Severity of the break
- Open or closed
List some common fracture types
- Open
- Impacted
- Comminuted
- Compression
- Greenstick
- Spiral
Open Fracture
- Also called a compound fracture
- Broken ends of the bone break through surface of skin
- Higher risk of infection
- Healing is much slower
- Commonly caused by high energy impacts e.g. falls/sports injuries
Impacted Fracture
- One end of the fractured bone is forcefully driven into the other
- Similar to compression fractures, except force is applied to both ends of the bone
- Common in RTA/high falls
Comminuted Fracture
- Bone breaks in a number of places - by splintering, crushing or breaking
- Pieces of the bone then lie between the two broken bone ends
- One of the most difficult fractures to treat
- More common in elderly patients - bones are more brittle
Compression Fractures
- Almost exclusive to body of the vertebrae
- Commonly occur when porous vertebral body is crushed, usually from one direction
- Can affect more than one vertebra at one time
- Occur in elderly patients suffering from osteoporosis
- Also, healthy individuals after fall from a significant height
Greenstick Fractures
- Occur in young, soft bone
- One side of the bone breaks and the other bends
- With age bones grow harder/more brittle - less likely to produce greenstick fracture
- Most during infancy/childhood when bones are soft + bend easily
Spiral Fractures
- Also called torsion fracture
- Occurs when bone is twisted apart
- Result of excessive twisting force to bone
- Normally only detected by X-Ray + often mistaken for oblique fracture
- Tends to run parallel with the axis of the bone
How is Vitamin D synthesised?
Vitamin D is made in the skin from 7-dehydrocholesterol under the influence of UV light.
How is Vitamin D involved in calcium homeostasis?
Vitamin D is carried in the bloodstream to the liver, where it is hydroxylated to Calcifediol (25-hydroxycholecalciferol). Circulating Calcifediol may then be hydroxylated to Calcitriol (1,25-dihydroxycholecalciferol), the biologically active for of Vitamin D, in the kidneys
Describe the action of RANK ligand
RANK ligand stimulates maturation of osteoclasts - binds to receptors, activation of osteoclasts, activated osteoclasts carry out bone resorption
Describe the inhibition of RANK ligand
OPG is produced in response to oestrogen, it is a decoy receptor for RANK ligand - binds to RANK so it is not recognised by receptor so there is no bone resorption
What is the function of OPG in a healthy person?
To stop constant bone resorption
Define bone healing
Progressive process, body promotes the protection + repair of areas surrounding a fractured bone.
How long does a fracture typically take to heal?
3-4 weeks for a simple fracture
What factors affect the healing period of a fracture?
Location, severity, angle and type of fracture
List the steps in bone repair
- Fracture haematoma formation
- Fibrocartilaginous callus formation
- Bony callus formation
- Bone remodelling
Describe fracture haematoma formation after a fracture
- Blood vessels around bone are damaged when bone breaks - blood haemorrhages into surrounding area
- In 6-8hrs, pool of blood develops at site of fracture called fracture haematoma
- Formation of haematoma causes blood vessels to constrict and stop further bleeding
- In response to formation of haematoma - blood cells die causing inflammation + swelling around area of injury
Describe fibrocartilaginous callus formation after a fracture
- Fibroblasts invade fracture site from periosteum
- Replicate, producing collagen fibres, intersperse w/ small BV and inflammatory cells to form granulation tissue
- Formation of granulation tissue leads to development of a fibrocartilaginous callus - islands of collagen fibres + cartilage
- Doesn’t provide structural rigidity - helps to bridge two ends of broken bone together
Describe bone remodelling after a fracture
- FInal stage - remodelling of repaired portion of bone
- Osteoclast activity increases - removes dead/damaged cells around bony callus
- Spongey bone is replaced by strong, thick, stable area of bone where fracture was
- No complications + bones are correctly aligned = remodelling occurs successfully, injury heals completely
Bone Remodelling in healthy bones.
Bone constantly undergoes remodelling - necessary for metabolic function in calcium/phosphorus storage.
Describe the processes involved with bone remodelling
- Bone resorption - loss of minerals + collagen fibres from bone under action of osteoclasts
- Bone deposition - new layers of bone tissue formed under action of osteoblasts
How is bone remodelling controlled?
Triggered by changes in mechanical forces or micro-damage and by hormonal responses to changes in calcium/phosphate
Explain the role of the physiotherapist in bone fracture healing
- Muscle assessment - following fracture, muscles around fracture sight weaken. Physio prescribe safe exercise program to restore strength + prevent secondary complications
- Joint mobilisation - stop joint stiffness
- Heat + electrotherapy
- Gait education - e.g. crutches
Describe the role of Physiotherapists in Osteoporosis treatment
- Can help strengthen bones + muscles
- Prevent bone thinning, reduce falls (improve balance), manage pain
- Weight bearing exercises (e.g. walking) can help to strengthen bones
Extracellular Matrix (ECM)
- Complex network of proteins and polysaccharides
- Secreted locally by cells and remain closely associated with them
Function of the ECM
Provides structural, adhesive and biochemical signalling signalling support
Give examples of areas where there is an ECM
- Bone
- Tendon
- Cartilage
- BV walls
- Cornea
- Basement Membrane
Describe the components of ECM
Fibres - e.g. collagen/elastin
and Ground Substances - e.g. Proteoglycans, Glycosaminoglycans
and Glycoproteins
List some types of ECM
- Loose networks e.g. submucosa, allows movement
- Tightly woven 3D e.g. skin, resilient properties
- Unidirectional aligned e.g. Tendon, mechanical properties
- Calcified e.g. bone, mechanical properties
Gives an example of ECM fibre synthesis
Collagen synthesised as procollagen, undergoes postranslational modifications (glycosylation, hydroxylation), assembled as a triple helix
Describe how Proteoglycans are synthesised in the ECM
- Core protein synthesised on RER
- Addition of polysaccharide as disaccharide repeats in Golgi
- Delivered to extracellular compartment by exocytosis
- Assembly with other ECM components
Describe ECM remodelling
Under action of Proteases, MMPs and Elastase, for wound repair, embryogenesis or angiogenesis.
Describe Basement Membrane/Basal Lamina structure
- A thin, tough sheet of ECM
- 3 layers - lamina lucida, lamina densa + lamina fibroreticularis
- Composed of collagen, laminin (glycoprotein), perlecan (proteoglycan), entactin + fibronectin (glycoprotein)
List some disorders of the Basement Membrane
- Cancer - epithelial tumours are malignant once they breach the BM
- Epidermolysis bullosa - failure in attachment of epidermis to BM
Rickets
- If epiphysis has not fused (in children/adolescents)
- Newly formed bone of the growth plate does not mineralise, causing the growth plate to become thick, wide + irregular
List the regions of the spine and number of vertebrae in each region
Cervical - 7 vertebrae Thoracic - 12 vertebrae Lumbar - 5 vertebrae Sacrum - 5 fused vertebrae Coccyx - 4 fused vertebrae
Describe the curves of the spine
- Lordosis (concave anterior) in the cervical and lumbar regions
- Kyphosis (concave anterior) in the thoracic and sacral regions
Describe the features of typical vertebrae
- Vertebral body
- Neural arch
- Vertebral foramen
- Pedicles
- Intervertebral foramina
- Laminae
- Transverse processes
- Inferior articular processes
- Superior articular processes
- Spinous process
Describe the facet joints between vertebrae
Formed from the inferior articular process of the vertebra above and the superior articular process from the vertebra below
Describe the structure of intervertebral discs
Centre is made of fluid filled, gelatinous Nucleus Pulposus which acts as a shock absorbed and is surrounded by the outer Annulus Fibrosis which is tougher and helps to contain the Nucleus Pulposus.
List the major ligaments which support the spine
- Nuchal ligaments
- Anterior longitudinal ligament
- Posterior longitudinal ligament
- Ligamenta Flava
Why is the spine curved
Increases mobility and ability to bear axial load
Which spinal curves are primary and which are secondary?
Thoracic and sacral kyphosis are primary curves, cervical and lumbar lordosis are secondary curves
When and why do the secondary curves of the spine form?
Spine is C-shaped at birth. Cervical lordosis develops at 6 months to allow lifting of head/head control. Lumbar lordosis develops at 10-14 months to allow standing/walking.
Scoliosis
Abnormal lateral curvature of the spine
Why is abnormally increased kyphosis often seen in the thoracic spine of elderly people?
Due to osteoporotic compression fractures
What parts of the spinal column are easily palpable?
The spinous processes of the vertebrae
What is the easily palpable spinous process in the cervical spine?
C7 (vertebra prominens)
What is the surface anatomy landmark for:
a) T3?
b) T7?
c) L4/5?
a) level of base of spines of scapulae
b) level of inferior angle of the scapula
c) level of iliac crests
What is significant about L1/2?
The spinal cord terminates, forming the Cauda Equina below
What is a dermatome?
An area of skin supplied by a specific spinal nerve root and spinal segment
Describe the movements that occur in the spinal column and where they occur
- Flexion/extension - cervical and lumbar (50% in cervical is at atlantoaxial joint).
- Rotation - thoracic.
- Lateral flexion - cervical, thoracic + lumbar
Where do most vertebral fractures occur and why?
At the junction between cervical and thoracic regions and thoracic and lumbar regions as the thoracic region is relatively immobile - biomechanical increase in stress between a stiff and moveable segment
What is a tendon reflex?
An involuntary muscle contraction response to the sudden stretch of its tendon. It can be used to test the integrity of a 2 neurone reflex arc innervated by a single segment of the spinal cord.
Myotome
Group of muscles supplied by a specific spinal nerve root
Describe which imaging modalities use ionising radiation
- X-Rays
- CT scans
- Fluoroscopy
- Nuclear Medicine
Describe the structure of C1 (atlas)
- Flat, wide superior articular surfaces which articulate with the occipital condyles
- Large vertebral foramen for brain stem/top of spinal cord
- Transverse foramen for the vertebral arteries
- No vertebral body
- Articular facet for odontoid process of axis (C2)
- Anterior + posterior arches
Describe the structure of C2 (axis)
- Odontoid process which articulates with C1 for movement of the head
- Transverse foramen for the vertebral arteries
- Vertebral body
Explain how to describe a radiology image
- Imaging Modality
- Plane/view (if X-ray)
- Area of body
- Side of body (L/R)
- Adult or child patient
- T1 or T2 weighted if MRI
Explain the difference between T1 and T2 weighted MRI scans
T1 - Fat shows up white, water (CSF) and air show up black
T2 - Water (CSF) shows up white, fat and air show up black
Describe structural differences between vertebrae of the different regions of the spine
Cervical
- Small vertebral body
- One vertebral foramina, 2 transverse foramina for vertebral arteries
- Small, bifid spinous processes
- Articular facets - superior faces posterosuperior, inferior faces anteroinferior
Thoracic
- Larger vertebral body
- Long, fairly thick spinous processes that mostly project inferiorly
- Have articular facets for ribs
- Articular facets - superior faces posterolateral, inferior faces anteromedial
Lumbar
- Largest vertebral body
- Short and blunt spinous processes - project posteriorly rather than inferiorly
- Articular facets - superior faces medial, inferior faces lateral
