Bone biology and fracture repair Flashcards
What could osteoprogenitor cells potentially develop into?
Fibroblasts, chondroblasts, or osteoblasts (-> osteocytes)
What is linked with the amount of mineral deposited into the bone?
Calcium homeostasis so PTH and calcitonin
What growth factors are involved in bone turnover following injury or inflammation?
TGFb bone resorption/ formation
IL-1 bone resorption
TNFa bone resorption
Prostaglandins bone resorption / formation
What are osteoclasts?
Multinucleate cells derived from the bone marrow.
What are osteoclasts responsible for?
Bone removal
Where are osteoclasts?
They lie in Howship’s lacunae on surfaces of bone being resorbed by enzymic digestion, in an extracellular vesicle.
What can impact osteoclast activity?
Calcitonin reduces activity.
Vitamin D increases activity.
PTH acts on osteoblasts which can mediate effects on osteoclasts - increasing their activity
What is bone matrix?
A mixture of osteoid and collagen
What is osteoid?
Composed of glycoprotein and proteoglycan that probably confers its propensity to mineralise.
Organisation of collagen in woven bone?
Haphazardly arranged fibres
Organisation of collagen in lamellar bone?
Fibres are in concentric or parallel bundles.
What do cement lines indicate?
Periods of bone resorption (appear scalloped) or deposition (smooth)
Effects of vitamin C on collagenous and non-collagenous proteins in bone.
Necessary to provide 4-hydroxyproline to stabilise collagen molecules.
Deficiency leads to a failure of collagen production.
Effects of vitamin D on collagenous and non-collagenous proteins in bone.
Both deficiency and excess produce lesions
Effects of vitamin A on collagenous and non-collagenous proteins in bone.
Excess produces degeneration of cartilage.
Effects of copper on collagenous and non-collagenous proteins in bone.
Deficiency interferes with cross-linking of collagen.
Effects of manganese on collagenous and non-collagenous proteins in bone
Affects bone matrix proteins -> ‘crooked calves’
What is the mineral in bone?
Hydroxyapatite
Two patterns of bone formation in the embryo
Intramembranous osteogenesis
Endochondral ossification
Intramembranous osteogenesis
Mesenchymal cells produce a matrix that is then mineralised
Endochondral ossification
Bone formation on a cartilaginous template
Mesenchyme > chondroblasts > chondrocytes > mineralised scaffold on which bone is deposited
In the later foetus vessels and cells including osteoblasts grow into the centre of a cartilaginous template to produce primary and secondary ossification centres. Bone formation then continues from these sites.
What is a physis
A seat of endochondral ossification that mediates growth in length of the bone.
What histological areas does the physis consist of?
Reserve zone
Proliferative zone
Hyperplastic zone
What does the metaphysis consist of?
Primary spongiosa
Secondary spongiosa
Modelled trabeculae
Bone modelling
Occurs in the young animal
Greatest modelling activity occurs in the metaphysis and the typical modelling sequence is activation/ resorption /formation but these are not coupled.
How is the adult bone shape produced?
Diaphyseal reduction
Bone remodelling
Occurs in adult animals, the mature skeleton remodels constantly throughout life.
Driven by the coupled activation - resorption - formation sequence.
Does not usually increase mass unless there is infarction and so new bone is laid down on dead trabeculae.
Where does bone remodelling occur?
The periosteal surface, which is normally expanding
Endosteal trabeculae which are generally resorptive surfaces
Haversian or inrtacortical surface where the changes are balanced
Chondrodysplasia
Genetic abnormality of development and remodelling
Abnormal cartilage growth results in reduced bone length but normal appositional growth so short, wide epiphyses.
Impact of growth hormone deficiency on bone development and remodelling
Leads to slowing of growth plate sequences and the metaphyseal surface may be sealed by a bony plate.
Impact of growth hormone excess on bone development and remodelling
Excessive growth of the physis stimulated, producing gigantism.
Impact of vitamin C deficiency on bone development and remodelling
Collagen abnormalities
Cartilage hypertrophy is slowed
Deficient osteoblastic activity with insufficient bone on the primary spongiosa, which then fractures under minimal weight bearing.
Impact of vitamin D deficiency on bone development and remodelling
There is a failure of mineralisation of cartilage matrix and hence a failure of endochondral ossification.
Bioelectric potentials
Induced by strain on the bone.
The response of mesenchyme cells is thus related to their polarity and occurs rapidly (can be radiographically visible in 2 weeks).
What happens when a whole bone is deformed?
The convex surface under tension is electropositive and the bone is resorbed.
The concave surface under compression in electronegative and bone is laid down.
Periosteal effects of a bone bending
When the bone is bent, the periosteum moves away from bone to the concave side and tension is released - bone is deposited.
On the convex side, periosteum is put under tension and bone resorption occurs.
Four common types of bone response to injury
Injured or stimulated periosteum results in new bone growth
Disruption of endochondral ossification interferes with production of metaphyseal bone - secondary effects such as microfractures may mask primary lesions
Mechanical forces on weakened metaphysis produces infractions which are compression fractures involving many trabeculae, without any gross discontinuity of bone. Results in the death of osteocytes and eventual resorption and replacement of bone tissue.
Fractures of bone shaft stimulate new bone formation from the periosteum and endosteum - often involving formation of soft tissue callus that then mineralises.
Traumatic fractures
Due to external agent/forces
Pathological fractures
Secondary to some underlying bone disease e.g. osteomyelitis or tumour
Fatigue fractures
Microfractuers in secondary spongiosa of metaphysis due to repeated low grade trauma
Direct repair (bone healing)
Seen when virtually no displacement of fractured ends e.g. contact healing at a microfracture when lamellar bone becomes deposited parallel to the bone cortex.
Gap healing (bone healing)
Occurs when lamellar bone is deposited by periosteal and endosteal osteoblasts perpendicular to the cortex e.g. at an osteotomy site.
The perpendicularly oriented lamellar bone is later replaced by lamellae running parallel to bone shaft.
Indirect repair (bone healing)
Occurs when there is movement of fragments at the fracture site.
The result is production of a callus and deposition of fibrous bone.
Five phases of long bone fracture repair
Integrated response of production and proliferation of specialised cells is required (cells become sensitised to messages from other cells)
Blood clot becomes organised by granulation tissue. Induced by mediator proteins to produce cartilage or woven bone.
Production of a callus follows - callus from both fragments eventually fuse.
Remodelling across the fracture site by osteoclasis followed by lamellar bone production.
Modelling of callus is the final phase - stimuli for modelling include stress of weightbearing and muscle pull.
Role of macrophages in fracture repair
Promote fibroplasia
Role of platelets in fracture repair
Release growth factors
Role of leucocytes in fracture repair
Produce IL-1 that has effects on various cell types.
Role of mast cells in fracture repair
Release angiogenic factors
Process of callus formation
Proliferation of the periosteum leads to a collar of callus tissue around the fracture ends – production and mineralisation of early trabeculae may be present within a week of the fracture occurring.
The cells then outstrip their blood supply and differentiate into chondrocytes with subsequent production of cartilage.
Collars of callus from each end of the fracture site grow towards each other and eventually fuse.
The cartilage is invaded by blood vessels and undergoes endochondral ossification to produce woven bone.
In addition to this (external) callus from the periosteum, an internal callus develops from the marrow cavities.
This is similar to the external callus but is smaller with little cartilage.
Complications of fracture repair
Poor alignment
Movement
Soft tissue interposition
Infection
Nutrition
Poor circulation/ischaemia
Periosteal damage
Poor alignment of fracture repair
Results in excess callus formation and deformity, leading to prolonged remodelling.
With comminution, dead fragments may be large and slow to be resorbed.
Wide separation of the fracture ends may also makes stable union impossible.
Movement after fracture repair
Continued movement of the two (or more) ends of bone at the fracture site leads to deposition of cartilage and reparative growth may cease before bony union is established.
This results in the formation of a pseudoarthrosis.
Soft tissue interposition after fracture repair
May physically prevent an osseous union being established or result in a pseudoarthritis.
Impacts of infection on fracture repair
Compound fractures in particular tend to be infected and purulent periostitis and osteomyelitis may supervene.
Acute bacterial infection inhibits attempts at bony repair and permits continued movement at the fracture site.
If infection is prolonged, bony union may not occur and a pseudoarthrosis may form.
Impacts of nutrition of fracture repair
Cachexia of whatever cause will delay healing and may produce a non-union or a weak repair
Effects of poor circulation/ischaemia on fracture repair
Failure to establish circulation in one end of the bone is a common cause of malunion.
Effects of periosteal damage on fracture repair
Excessive tearing and injury to the periosteum will severely compromise the formation of callus and inhibit healing.
What fracture is most likely to have a dead fragment?
Proximal femur fracture with a slipped capital femoral epiphysis
The neck and head of femur are vascularised by vessels of the articular capsule. These are often torn when fractures occur at this site and the femoral head undergoes avascular necrosis.
How does healing occur when one fracture fragment is dead?
Fibrovascular tissue together with osteogenic cells crosses the fracture line and re-vascularises the marrow space. Woven bone is deposited on the surface of the dead trabeculae.
Thus, initially the bone mass is increased and only gradually is dead bone resorbed and replaced by living bone. Remodelling will eventually replace dead bone and re-establish normal morphology.
What is a sequestrum?
A piece of dead bone that has become separated during the process of necrosis from normal or sound bone. Happens particularly in the abscence of asepsis.
What is the pathological process of a sequestrum forming?
Infection in the bone leads to an increase in intramedullary pressure due to inflammatory exudates.
The periosteum becomes stripped from the osteum, leading to vascular thormbosis.
Bone necrosis follows due to lack of blood supply.
Sequestra are formed.
Why is chronic osteomyelitis difficult to treat?
Sequestra are avascular so antibiotics which travel to sites of infeciton via the bloodstram poorly penetrate them.
When using a bone graft, how long will it be until the onset of a homograft reaction?
About 10 days
How does the reparative process using a bone graft work?
Similar to a fracture repair where one fragment is dead - a fresh homograft reaction involves a few cells surviving until the onset of reaction at about 10 days.
What must you have for a bone graft to be successful?
A good blood supply.
How does a bone graft work?
Even with a fresh autograft, the bulk of the bone is necrotic due to deprivation of its blood supply, but some surface cells, periosteal and endosteal cells survive and contribute to the formation of new bone.
Adequate vascular supply is critical.
The graft becomes vascularised from the periphery by new vessels and osteoprogenitor cells.
Woven bone is laid down on the graft and joined by new bony trabeculae to surrounding bone.
Which bone graft is most osteogenic and so best for filling spaces?
An autogenous graft of cancellous bone chips.
Which bone graft is better for fixation?
A homologous bone graft - vascular invasion is slower ad new bone is laid down in the dead trabeculae adding to bone mass and strength.
