Fracture Healing

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Inflammatory response 

– Time of injury to 24-72 hours

  • Injured tissues and platelets release vasoactive mediators, growth factors and other cytokines.  

  • These cytokines influence cell migration, proliferation, differentiation and matrix synthesis.  

  • Growth factors recruit fibroblasts, mesenchymal cells & osteoprogenitor cells to the fracture site.

  • Macrophages, PMNs & mast cells (48hr) arrive at the fracture site to begin the process of removing the tissue debris. 

 

Important cytokines in bone healing: 

BMP

Osteoinductive, induces metaplasia of mesenchymal cells into osteoblasts

Target cell for BMP is the undifferentiated perivascular mesenchymal cell

TGF-b

Induces mesenchymal cells to produce type II collagen and proteoglycans

Induces osteoblasts to produce collagen

PDGF

Attracts inflammatory cells to the fracture site

FGF

Stimulates fibroblast proliferation

IGF-II

Stimulates type I collagen production, cartilage matrix synthesis and cellular proliferation

IL-1

Attracts inflammatory cells to the fracture site

IL-6

Attracts inflammatory cells to the fracture site

 

Reparative response 

– 2 days to 2 weeks

  • Vasoactive substances (Nitric Oxide & Endothelial Stimulating Angiogenesis Factor) cause neovascularisation & local vasodilation

  • Undifferentiated mesenchymal cells migrate to the fracture site and have the ability to form cells which in turn form cartilage, bone or fibrous tissue.  

  • The fracture haematoma is organised and fibroblasts and chondroblasts appear between the bone ends and cartilage is formed (Type II collagen).

  • The amount of callus formed is inversely proportional to the amount of immobilisation of the fracture.

  • In fractures that are fixed with rigid compression plates there can be primary bone healing with little or no visible callus formation.

fracture-healing

Types of callus:

External (bridging) callus

From the fracture haematoma

Ossifies by endochondral ossification to form woven bone

Internal (medullary) callus

Forms more slowly and occurs later

Periosteal callus

Forms directly from the inner periosteal cell layer. 

Ossifies by intramembranous ossification to form woven bone

 

Remodelling: 

– Middle of repair phase up to 7 years

  • Remodelling of the woven bone is dependent on the mechanical forces applied to it (Wolff’s Law – 'form follows function')

  • Fracture healing is complete when there is repopulation of the medullary canal

  • Cortical bone

    • Remodelling occurs by invasion of an osteoclast “cutting cone” which is then followed by osteoblasts which lay down new lamellar bone (osteon)

  • Cancellous bone

    • Remodelling occurs on the surface of the trabeculae which causes the trabeculae to become thicker

 

Factors influencing bone healing

Systemic

Local

Age

Degree of local trauma

Hormones

Degree of bone loss

Functional activity

Vascular injury

Nerve function

Type of bone fractured

Nutrition

Degree of immobilisation

Drugs (NSAID)

Infection

 

Local pathological condition

 

Hormonal influences on bone healing

Hormone

Effect

Mechanism

Cortisone

Decr.

Decreased callus production

Calcitonin

Incr.

Unknown

TH/PTH

Incr.

Bone remodelling

GH

Incr.

Increased callus volume

Androgens

Incr.

Increased callus volume

   

Electricity and fracture healing

  • Stress generated potentials

  • Serve as signals that modulate cellular activity

  • Piezoelectric effect and streaming potentials are examples of stress generated potentials

  • Piezoelectric effect: charges in tissues are changed secondary to mechanical forces

  • Streaming potentials: occur when electrically charged fluid is forced over a tissue (cell membrane) with a fixed charge

  • Transmembrane potentials: generated by cellular metabolism

  • Fracture Healing

    • Direct current stimulates an inflammatory like response

    • Alternating current affects cyclic AMP, collagen synthesis and calcification during the repair phase

    • Pulsed electromagnetic fields initiate calcification of fibrocartilage

  Ultrasound

  • Can decrease the time to clinical healing and radiological union 

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