1. Basic Science of Bone Healing Almas Khan SpR Trauma Term

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

3. Bone Healing is a Continuum Inflammation Repair: soft/hard callus Remodelling

4. Stages of fracture healing Inflammation 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

5. Inflammation Cytokines attract pmn leucocytes, mphage, lymphocytes Resorb dead tissue, release more cytokines, stimulate angiogenesis Fibroblasts along the fibrillar network form granulation tissue

6. Stages of fracture healing Inflammation 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

7. 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

8. 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

9. 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

10. Repair Mechanical stages of bone healing Failure site 1.at # 2.At # 3.Partially away from # 4.Through previously normal tissue “Excessive repair” Stiffness curve 1.Soft tissues 2.Hard tissues 3.Hard tissues 4.Hard tissues

11. Stages of fracture healing Inflammation 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

12. 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

13. Factors in fracture healing Blood supply Nicotine NSAIDs Nutrition Age Comorbidity Vascular injury Soft tissue envelope Functional Level Nerve Function Hormones Growth Factors Sterility Local pathology eg Ca Type of bone Bone loss Soft tissue attachments to bone Stability Site/location Energy Bone Loss

14. 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

15. Primary Bone Healing

16. Fixation methods and mode of healing

17. 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%

18. 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.

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