FRACTURE HEALING

1. FRACTURE HEALING Presented By Mrs. Margaret Mala, Msc Nursing Assistant Professor, Department of Child Health Nursing Annammal college of nursing.

2. Fracture • Fracture is defined as a break in the continuity of bone • Fracture results in loss of its mechanical stability and also partial destruction of blood supply • Healing means to make whole or sound again, to cure, leaving a scar behind. But following fracture a scar is not formed, instead a bone has formed a new at the original fracture site. So rather than bone healing the appropriate nomenclature would be BONE REGENERATION

3. TYPES OF FRACTURES • ON BASIS OF ETIOLOGY - Traumatic fracture - pathologic fractures due to some diseases - stress fracture • ON BASIS OF DISPLACEMenT - undisplaced - displaced translation ( shift ) angulation ( tilt ) rotation ( twist )

4. ON BASIS OF RELATIONSHIP WITH EXTERNAL ENVIRONMENT - simple / closed fracture - open fracture • ON BASIS OF PATTERN - transverse - oblique - spiral - comminuted - segmental

6. HEALING AFTER FRACTURE FIXATION 1. DIRECT/PRIMARY: • Mechanism of bone healing seen when there is no motion at the fracture site (i.e. rigid internal fixation). • Does not involve formation of fracture callus. • Osteoblasts originate from endothelial and perivascular cells.

7. 2. INDIRECT/SECONDARY: • Mechanism for healing in fractures that are not rigidly fixed. • Bridging periosteal (soft) callus and medullary (hard) callus re-establish structural continuity. • Callus subsequently undergoes endochondral ossification.

8. TYPES OF BONE HEALING 1. PRIMARY • CONTACT HEALING: When there is direct contact between the cortical bone ends, lamellar bone forms directly across the fracture line , parallel to long axis of the bone, by direct extension of osteons. • GAP HEALING: Osteoblasts differentiate and start depositing osteoids on the exposed surfaces of fragment ends, mostly without a preceding osteoclasticresorption which is later converted into the lamellar bone

9. 2. SECONDARY: It is usual type consisting of formation of callus either of cartilaginous or fibrous. This callus is later replaced by lamellar bone. It is comparable to healing of soft tissue by filling of gaps with vascular granulation tissue

10. STAGES OF FRACTURE HEALING • There are 3 major phases with sub divisions: • A. Reactive Phase: • i. Fracture and inflammatory phase. • ii. Stage of hematoma formation. • iii. Granulation tissue formation. • B. Reparative Phase: • iv. Cartilage Callus formation. • v. Lamellar bone deposition. • C. Remodeling Phase: • vi. Remodeling to original bone contour.

11. Components of Bone Formation • Cortex • Periosteum • Bone marrow • Soft tissue

12. A.REACTIVE PHASE • I .Fracture & inflammatory phase : After fracture the first change seen by light and electron microscopy is the presence of blood cells within the tissues which are adjacent to the injury site. Soon after fracture, the blood vessels constrict, stopping any further bleeding

13. ii. Stage of Hematoma formation: Within a few hours after fracture, the extravascular blood cells form a blood clot, known as a hematoma. All of the cells within the blood clot degenerate and die. The fracture hematoma immobilizes & splints the fracture. The fracture haematoma provides a fibrin scaffold that facilitates migration of repair cells.

14. iii. Granulation Tissue Formation: Within this same area, the fibroblasts survive and replicate. They form a loose aggregate of cells, interspersed with small blood vessels, known as granulation tissuewhich grows forward, outside and inside the bone to bridge the fracture. They are stimulated by vasoactive mediators like serotonin and histamine

15. B. REPARATIVE PHASE • iv. Cartilage Callus formation : Days after the # the periosteal cells proximal to the fracture gap and fibroblasts develop into chondroblasts which form hyaline cartilage. The periosteal cells distal to the fracture gap develop into osteoblasts which form woven bone. These 2 tissues unite with their counterparts and culminate into new mass of heterogenous tissue called Fracture Callus restoring some of its original strength.

16. v. Lamellar bone deposition: Or consolidation ..where hyaline cartilage and woven bone is replaced by lamellar bone. This process is called Endochondral ossification. At this point, the mineralized matrix is penetrated by channels, each containing a microvessel and numerous osteoblasts.  This new lamellar bone is in the form of trabecular bone which restores bone’s original strength

17. C. REMODELLING PHASE • vi. Remodelling to original bone contour: The remodeling process substitutes the trabecular bone with compact bone. The trabecular bone is first resorbed by osteoclasts, creating a shallow resorption pit known as a "Howship's lacuna". Then osteoblasts deposit compact bone within the resorption pit. Eventually, the fracture callus is remodelled

19. FACTORS INFLUENCING BONE HEALING • LOCAL FACTORS • CHEMICAL FACTORS. • VASCULAR FACTORS. • SYSTEMIC FACTORS • ELECTROMAGNETIC FACTORS • TREATMENT FACTORS

20. 1.LOCAL FACTORS A. Type of bone: Cancellous (spongy) bone or cortical bone. B. Degree of Trauma: Extensive soft tissue injury and comminuted #‘s V/s Mild contusions C. Vascular Injury:  Inadequate blood supply impairs healing. Especially vulnerable areas are the femoral head, talus, and scaphoid bones.

21. D. Degree of Immobilization: Immobilized for vascular ingrowth and bone healing to occur. Repeated disruptions of repair tissue, especially to areas with marginal blood supply or heavy soft tissue damage, will impair healing. E. Type of Fractures: Intraarticular fractures communicate with synovial fluid, which contains collagenases that retard bone healing Open fractures result in infections Segmental fractures have disrupted blood supply. F.Soft Tissue Interposition: G.others: Bone death caused by radiation, thermal or chemical burns or infection.

22. 2.CHEMICAL FACTORS 1.MESSENGER 2.GROWTH 3.PERMEABILITY SUBSTANCES FACTORS FACTORS -Serotonin -Transforming GF -Proteases • -Prostaglandins -Fibroblast GF - Amines Polypeptides - Platelet derived GF -Histamines -BMP -Thromboxane -Insulin like GF

23. C.LEUKOTRINES-Stimulate osteoblastic bone formation and enhance the capacity of isolated osteoclasts to form resorption pits • 1.MESSENGER SUBSTANCE: A.CYTOKINES- -IL-1,4,6,11, macrophage and granulocyte/macrophage (GM) (CSFs) & (TNF) stimulate bone resorption. -IL-1 ,6 synthesis is decreased by estrogen B. PROSTAGLANDINS of the E series- -Stimulate osteoblastic bone formation and inhibit activity of isolated osteoclasts.

24. 2.GROWTH FACTORS: A. Transforming growth factor(TGF): Superfamily of growth factors (~34 members) Act on serine/threonine kinase cell wall receptors Promotes proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes Stimulates both endochondral and intramembranous bone formation and collagen type 2 synthesis. B.Fibroblast growth factors(FGF): Both acidic (FGF-1) and basic (FGF-2) forms Increase proliferation of chondrocytes and osteoblasts Enhance callus formation & stimulates angiogenesis.

25. C.Platelet derived growth factor(PDGF): A dimer, genes PDGF-A and PDGF-B Stimulates bone cell growth Increases type I collagen synthesis by increasing the number of osteoblasts. PDGF-B stimulates bone resorption. D.Insulin like growth factor(ILGF): Two types, IGF1 &IGF2, out of which IGF1 is produced in liver and stimulated by growth hormone. Stimulates bone collagen & matrix synthesis and replicates osteoblasts . It also inhibits collagen degradation.

26. E.BoneMorphogenic Proteins (BMP): BMP was discovered by Marshall Urist in 1965. They are Osteoinductive proteins initially isolated from demineralized bone matrix FUNCTIONS: 1. Induce cell differentiation : BMP 3(osteogenin). 2. Promote endochondral ossification: BMP 2 & 7. 3. Regulate extracellular matrix production :BMP1. 4.Increase fusion rates in Spinal fusions): BMP 2 5.Non unions: BMP 7 as good as bone grafting These are included in the TGF-β family except BMP 1. Must be applied locally because of rapid systemic clearance .

27. 3.PERMEABILITY FACTORS: -Protease – Plasmin , Kalikrein, Globulin permeability factor. -Polypeptides –leucotaxime, Bradykinin, Kallidin -Amines – Adrenalin, nor-adrenalin, Histamine These factors work in ways that : • Increase capillary permeability • Alteration in diffusion mechanism in intracellular matrix • Cellular migration • Proliferation & differentiation • New blood vessel formation • Matrix synthesis • Growth & development

28. 3.VASCULAR FACTORS • Metalloproteinases Degrade cartilage and bones to allow invasion of vessels • Angiogenic factors: Vascular-endothelial growth factors mediate neo-angiogenesis & endothelial-cell specific mitogens C. Angiopoietin (І & ІІ) Regulate formation of larger vessels and branches.

29. 4.SYSTEMIC FACTORS A.Age:  Young patients heal rapidly and have a remarkable ability to remodel V/S old . B.Nutrition: An adequate metabolic stage with sufficient carbohydrates and protein is necessary. C.Systemic Diseases:  And those causing an immunocompromised state will likely delay healing. Illnesses like Marfan’s syndrome and Ehlers-Danlos syndrome cause abnormal musculoskeletal healing

30. D.HORMONES: • Estrogen Stimulates fracture healing through receptor mediated mechanism. • Thyroid hormones Thyroxine and triiodothyronine stimulate osteoclastic bone resorption. • Glucocorticoids Inhibit calcium absorption from the gut causing increased PTH and therefore increased osteoclastic bone resorption. • Parathyroid Hormone • Growth Hormone: Mediated through IGF-1 (Somatomedin-C) Increases callus formation and fracture strength

31. 5.ELECTROMAGNETIC FACTORS In vitro bone deformation produces piezoelectric currents and streaming potentials. Electromagnetic (EM) devices are based on Wolff’s Law that bone responds to mechanical stress: Exogenous EM fields may simulate mechanical loading and stimulate bone growth and repair

32. 6.TREATMENT FACTORS • APPOSITION OF FRACTURE FRAGMENTS. • LOADING AND MICROMOTION . • FRACTURE STABILIZATION. • RIGID FIXATION. • BONE GRAFTING.

33. RECENT ADVANCES • GROWTH FACTOR THERAPY(3) Due to their ability to stimulate proliferation and differentiation of mesenchymal and osteoprogenitor cells they have shown great promise for their ability to promote fracture repair . • APPLICATION OF PLATELET RICH PLASMA(4) Injecting platelet rich plasma at fracture site helps in fracture healing . • TISSUE ENGINEERING, STEM CELLS AND GENE THERAPIES(5) In past decade tissue culture and stem cells have been implicated in enhancing fracture healing and articular cartilage regeneration.

34. Nanotechnology(1) based on understanding cell-implant interactions. Cells do not interact directly with an implant but instead interact through a layer of proteins that absorb almost instantaneously to the implant after insertion. Scientists have improved numerous implant materials, including titanium and titanium alloys, porous polymers, bone cements and hydroxyapatite, by placing nanoscale features on their surfaces. The bulk materials' properties remain unchanged, maintaining their desirable mechanical properties, but the surface changes enhance the interactions with proteins. This causes bone-forming cells to adhere to the implant and activates them to grow more bone.

35. COMPLICATIONS OF FRACTURE HEALING • MALUNION • DELAYED UNION • NONUNION

36. THANK YOU