Basic Science of Bone Healing

Almas KhanSpR

Trauma Term

Content

• Introduction• Stages of fracture repair• Biomechanical steps• Growth factors• Factors influencing bone healing• Primary Bone Healing• Hormonal effects• US, Radiation• (Quiz)

Bone Healing is a ContinuumInflammation

Repair: soft/hard callus

Remodelling

Stages of fracture healing

Inflammatio

n•Bleeding•Haematoma•Haemopoeitic stem cells•Growth factors•Fibroblasts•Mesenchymal cells•Osteoprogenitor cells•Granulation tissue•Osteoblasts from osteogenic precursor cells and / fibroblasts proliferate

Repair

•1° Callus within 2/52•Bridging (soft) Callus if space•Replaced by enchondral ossification by woven bone (hard callus)

•Slower forming medullary callus•Type II collagen, then Type 1 collagen expression in unstable # patterns

•Primary bone healing with no callus

Remodelling

•Begins during middle of repair phase•Continues for up to 7 years•According to Wolff’s Law based on stresses•#healing is complete when there is repopulation of the marrow space

Inflammation

• Cytokines attract pmn leucocytes, mphage, lymphocytes

• Resorb dead tissue, release more cytokines, stimulate angiogenesis

• Fibroblasts along the fibrillar network form granulation tissue

Stages of fracture healing

Inflammatio

n•Bleeding•Haematoma•Haemopoeitic stem cells•Growth factors•Fibroblasts•Mesenchymal cells•Osteoprogenitor cells•Granulation tissue•Osteoblasts from osteogenic precursor cells and / fibroblasts proliferate

Repair

•1° Callus within 2/52•Bridging (soft) Callus if space•Replaced by enchondral ossification by woven bone (hard callus)

•Slower forming medullary callus•Type II collagen, then Type 1 collagen expression in unstable # patterns

•Primary bone healing with no callus

Remodelling

•Begins during middle of repair phase•Continues for up to 7 years•According to Wolff’s Law based on stresses•#healing is complete when there is repopulation of the marrow space

Repair

• Heamatoma replaced by callus

• Fibroblasts, chondroblasts, osteoblasts ; with their matrices

• Enchondral ossification in centre, direct generation of woven bone from cambium layer of periosteum- intrammbranous ossification

Repair

• Exact interaction of factors poorly understood

• Role of cytokines:

• Fibroblastic growth factor stimulates angiogenesis

• Transforming growth factor β initiates chondroblast and osteoblast formation

• Transforming growth factor β also stimulates enchondral classification

Repair

• Early fracture callus – Consists of

glycosaminoglycans and type II and III collagen

• Transformation to hyaline and fibrocartilage– Cartilage specific

proteoglycans and type II collagen become more abundant

• Intramemebranous and woven bone formation indicated by high concentrations of Alkaline phsphatase, Type I collage and osteocalcin

Repair

• Mechanical stages of bone healing

• Failure site1. at #2. At #3. Partially away from #4. Through previously

normal tissue

“Excessive repair”

• Stiffness curve1. Soft tissues2. Hard tissues3. Hard tissues4. Hard tissues

Stages of fracture healing

Inflammatio

n•Bleeding•Haematoma•Haemopoeitic stem cells•Growth factors•Fibroblasts•Mesenchymal cells•Osteoprogenitor cells•Granulation tissue•Osteoblasts from osteogenic precursor cells and / fibroblasts proliferate

Repair

•1° Callus within 2/52•Bridging (soft) Callus if space•Replaced by enchondral ossification by woven bone (hard callus)

•Slower forming medullary callus•Type II collagen, then Type 1 collagen expression in unstable # patterns

•Primary bone healing with no callus

Remodelling

•Begins during middle of repair phase•Continues for up to 7 years•According to Wolff’s Law based on stresses•#healing is complete when there is repopulation of the marrow space

Remodelling

• Continuous process of Haversian remodelling

• Osteoclastic resorption, possibly guided by electrical or mechanical strain fields remove extraneous peripheral bone

• An example of Wolff’s Law

Factors in fracture healing

Blood supply

NicotineNSAIDs

Nutrition

AgeComorbidity

Vascular injurySoft tissue envelope

Functional LevelNerve Function

HormonesGrowth Factors

SterilityLocal pathology

eg CaType of bone

Bone loss

Soft tissue attachments to

boneStability

Site/locationEnergy

Bone Loss

Primary Bone Healing

• Temporary acceleration of Haversian remodelling

• Only occurs with rigid fixation

• No callus• Lag period• Osteoclast Jumping

Distance

• Bone metabolising units– Linear resorption rate of

50 microns per day– X-section 200 microns– Walls of osteon lined by

osteoblasts– Circumferentially appose

new osteoid at 1 micron per day

– New osteon (3mm long x 90 microns wall thickness) will take 3-4 months

Primary Bone Healing

Fixation methods and mode of healing

Low intensity ultrasound

• pulsed low-energy ultrasound used for 20 mins daily may enhance fracture healing, via enhanced angiogenesis and the induction of IL8, basic FGF and VEGF

• Reports say healing time reduced by up to 38%

Radiation• Delays bone healing, delays healing of all tissues within irradiated field• Approximately 50% reduction in bending and twisting moments in large

animal model for revascularised bone graft healing. Similar results for adjuvant and neo adjuvant radiotherapy.

• Irradiation of mature bone results in vascular and cellular changes best characterized as osteopenia.

• Irradiated bone is susceptible to subsequent fracture, septic osteoradionecrosis, and sarcoma formation.

• Irradiation of fractured bones may result in delayed healing or non-union of the fracture; however, in some patients, healing will occur.

• Pathological fractures associated with neoplasia may heal after radiation therapy if internal fixation is employed.

• Irradiation of growing bone typically results in retardation of longitudinal growth.

Thank You