fracture healing presentation for postgraduates

fracture healing and its stages

1. Dr. BHOSALE SUMIT Junior Resident-1 Dept. of Orthopedics Dr . PRAMOD SARKELWAD DR.DEEPAK AGRAWAL ASSO. Professor and HOU PROF. and HOD Dept. of Orthopaedics Dept. Of Orthopaedics DUPMC & H DUPMC & H

2. FRACTURE HEALING AND STAGES OF HEALING

3. Fracture is a break in the structural continuity of bone or periosteum. The healing of fracture is in many ways similar to the healing in soft tissue wounds except that the end result is mineralized mesenchymal tissue i.e. BONE. Fracture healing starts as soon as bone breaks and continues modelling for many years. INTRODUCTION

4. The essential event in fracture healing is the creation of a bony bridge between the two fragments which can be readily be built upon and modified to suit the particular functional demands .

5. Types of Bone Lamellar Bone - Orderly cellular distribution Collagen fibers arranged in parallel layers Normal adult bone Woven Bone or immature bone (non-lamellar) Randomly oriented collagen fibers In adults, seen at sites of fracture healing, tendon or ligament attachment and in pathological conditions

6. Cortical bone - Comprised of osteons ( Haversian systems) runs longitudinally Osteons communicate with medullary cavity by Volkmann’s canals that run horizontally Lamellar Bone

7. Haversian System Picture courtesy Gwen Childs, PhD. osteon Haversian canal osteocyte Volkmann’s canal

8. Woven Bone Coarse with random orientation Weaker than lamellar bone Normally remodeled to lamellar bone Figure from Rockwood and Green’s: Fractures in Adults, 4 th ed

9. Bone Composition Cells Osteocytes Osteoblasts Osteoclasts Extracellular Matrix Organic (35%) Collagen (type I) 90% Osteocalcin , osteonectin , proteoglycans , glycosaminoglycans , lipids (ground substance) Inorganic (65%) Primarily hydroxyapatite Ca 5 (PO 4 ) 3 (OH) 2

10. Osteoblasts Derived from mesenchymal stem cells Line the surface of the bone and produce osteoid Immediate precursor is fibroblast-like preosteoblasts Picture courtesy Gwen Childs, PhD.

11. Osteocytes Osteoblasts surrounded by bone matrix trapped in lacunae Function poorly understood regulating bone metabolism in response to stress and strain Picture courtesy Gwen Childs, PhD.

12. Osteoclasts Derived from hematopoietic stem cells ( monocyte precursor cells) Multinucleated cells whose function is bone resorption Reside in bone resorption pits ( Howship’s lacunae) Parathyroid hormone stimulates receptors on osteoblasts that activate osteoclastic bone resorption Picture courtesy Gwen Childs, PhD.

13. Components of BONE Formation Cortex Periosteum Bone marrow Soft tissue

14. Prerequisites for Bone Healing Adequate blood supply Adequate mechanical stability

15. Mechanisms of Bone Formation Cutting Cones Intramembranous Bone Formation Endochondral Bone Formation

16. Cutting Cones Primarily a mechanism to remodel bone Osteoclasts at the front of the cutting cone remove bone Trailing osteoblasts lay down new bone Courtesy Drs. Charles Schwab and Bruce Martin

17. Intramembranous (Periosteal) Bone Formation Mechanism by which a long bone grows in width Osteoblasts differentiate directly from preosteoblasts and lay down seams of osteoid Does NOT involve cartilage . It mainly forms cancellous bone.

18. Endochondral Bone Formation Mechanism by which a long bone grows in length Osteoblasts line a cartilage precursor The chondrocytes hypertrophy, degenerate and calcify (area of low oxygen tension) Vascular invasion of the cartilage occurs followed by ossification (increasing oxygen tension)

19. Blood Supply Long bones have four blood supplies Nutrient artery ( intramedullary ) Periosteal vessels Metaphyseal vessels Epiphysial vessels Nutrient artery Metaphyseal vessels Periosteal vessels Figure adapted from Rockwood and Green, 5 th Ed

20. Nutrient Artery Normally the major blood supply for the diaphyseal cortex (80 to 85%) Enters the long bone via a nutrient foramen Forms medullary arteries up and down the bone

21. Vascular Response in Fracture Repair Fracture stimulates the release of growth factors that promote angiogenesis and vasodilation Blood flow is increased substantially to the fracture site Peaks at two weeks after fracture

22. Fracture healing Introduction Fracture healing is a complex process that requires the recruitment of appropriate cells (fibroblasts, macrophages, chondroblasts , osteoblasts , osteoclasts ) and the subsequent expression of the appropriate genes (genes that control matrix production and organization, growth factors, transcription factors) at the right time and in the right anatomical location

23. Inflammation stage of haematoma formation Repair stage of granulation tissue stage of callus formation Remodelling Stages of Fracture Healing

24. Duration The inflammatory phase peaks within 48 hours and is quite diminished by 1 week after fracture. The reparative phase becomes activated within the first few days after fracture and persists for 2-3 months. The remodelling phase lasts for many years

25. Disruption of blood vessels in the bone, marrow, periosteum , and surrounding tissue disruption at the time of injury results in the extravasation of blood at the fracture site and the formation of a hematoma Local vessels thrombose causing bony necrosis at the edges of the fracture Increased capillary permeability results in a local inflammatory milieu Osteoinductive growth factors stimulate the proliferation and differentiation of mesenchymal stem cells

26. Reparative phase The reparative phase, which usually begins 4 or 5 days after injury, is characterized by the invasion of pluripotential mesenchymal cells, which differentiate into fibroblasts, chondroblasts , and osteoblasts and form a soft primary fracture callus . Proliferation of blood vessels (angiogenesis) within the periosteal tissues and marrow space helps route the appropriate cells to the fracture site and contributes to the formation of a bed of granulation tissue .

27. Mesenchymal cells at the fracture site proliferate differentiate and produce the fracture callus Two types of callus : Primary callus or Soft callus – forms in the central region in which there is relatively low oxygen tension . The primary callus may consist of cartilage, fibrous tissue, osteoid , woven bone, and vessels. If the primary callus is successful, healing progresses to the stage of bridging callus or hard callus. Hard callus – formed at the periphery of the callus by intermembranous bone formation

28. Periosteal callus forms along the periphery of the fracture site Intramembranous ossification initiated by preosteoblasts Intramedullary callus forms in the center of the fracture site Endochondral ossification at the site of the fracture hematoma Chemical and mechanical factors stimulate callus formation and mineralization

29. Repair Figure from Brighton, et al, JBJS-A, 1991.

30. Remodeling The biochemical composition of the fracture callus matrix changes as repair progresses. The cells replace the fibrin clot with a loose fibrous matrix containing glycosaminoglycans , proteoglycans , and types I and III collagen In many regions they convert this tissue to more dense fibrocartilage or hyaline-like cartilage. With formation of hyaline-like cartilage, type II collagen, cartilage-specific proteoglycan and link protein content increase.

31. Woven bone is gradually converted to lamellar bone Medullary cavity is reconstituted Stability of the fracture fragments progressively increases . eventually clinical union occurs that is, the fracture site becomes stable and pain-free. Radiographic union occurs when plain radiographs show bone trabeculae or cortical bone crossing the fracture site, and often occurs later than clinical union . Despite successful fracture healing, the bone density of the involved limb may be decreased for years

32. Fracture healing is divided according to bone-- Cortical bone of the shaft. Cancellous bone of the metaphyseal region of the long bones and the small bones. FRACTURE HEALING TYPES

33. STAGES OF BONE HEALING : Stage 0: Injury and hematoma formation. Stage 1: Inflammation. Stage 2: Soft callus formation. Stage 3: Hard callus formation. Stage 4: Remodelling.

34. Stage 0: Injury and hematoma formation. Duration : 0-4 hours.

35. Tissue destruction and Hematoma formation Torn blood vessels hemorrhage A mass of clotted blood (hematoma) forms at the fracture site Site becomes swollen, painful, and inflamed

36. Tissue destruction and Hematoma formation

37. Stage 1 : Stage of inflammation. Duration : 1-7 days.

38. INFLAMATION AND CELLULAR PROLIFERATION Within 8 hours inflammatory reaction starts. Proliferation and Differntiation of mesenchymal stem cells. Secretion of TGF-B , PDGF and various BMP factors.

39. Stage 2 : Stage of soft callus formation. Duration : 2- 3 weeks.

40. Callus Formation Fibrocartilaginous callus forms Granulation tissue (soft callus) forms a few days after the fracture Capillaries grow into the tissue and phagocytic cells begin cleaning debris

41. Callus Formation Theory OSTEOPROGENITOR CELL present in all ENDOSTEAL and SUBPERIOSTEAL surface give rise to CALLUS. CALLUS arises from NON-SPECIALISED CONNECTIVE TISSUE CELLS in the region of fracture which are induced into conversion to OSTEOBLASTS.

42. Callus Formation

43. Stage 3 : Stage of Hard callus formation. Duration : 3 – 12 weeks.

44. STAGE OF CONSOLIDATION New bone trabeculae appear in the fibrocartilaginous callus Fibrocartilaginous callus converts into a bony (hard) callus Bone callus begins 3-4 weeks after injury, and continues until firm union is formed 2-3 months later

45. Stage 4 : Stage of Remodelling. Duration: Months to years.

46. STAGE OF REMODELLING Excess material on the bone shaft exterior and in the medullary canal is removed Compact bone is laid down to reconstruct shaft walls

47. Schematic drawing of the callus healing process. Early intramembranous bone formation (a), growing callus volume and diameter mainly by enchondral ossification (b), and bridging of the fragments (c). Figure from Brighton, et al, JBJS-A, 1991

48. A: Roentgenogram of a callus healing in a sheep tibia with the osteotomy line still visible (6 weeks p.o.). B: Histological picture of a sheep tibia osteotomy (fracture model) after bone bridging by external and intramedullary callus formation. A few areas of fibrocartilage remain at the level of the former fracture line (dark areas).

49. Types for Bone Healing Direct (primary) bone healing Indirect (secondary) bone healing

50. Direct fracture healing: • Occurs by absolute stability . • Primarty healing occurs. • No callus formation. • Heal by direct osteonal remodelling.

51. Direct Bone Healing Mechanism of bone healing seen when there is no motion at the fracture site (i.e. absolute stability) Does not involve formation of fracture callus Osteoblasts originate from endothelial and perivascular cells

52. Components of Direct Bone Healing Contact Healing Direct contact between the fracture ends allows healing to be with lamellar bone immediately Gap Healing Gaps less than 200-500 microns are primarily filled with woven bone that is subsequently remodeled into lamellar bone Larger gaps are healed by indirect bone healing (partially filled with fibrous tissue that undergoes secondary ossification)

53. Direct Bone Healing Figure from http://www.vetmed.ufl.edu/sacs/notes

54. Direct fracture healing

55. Absolute stability in Direct fracture healing examples : a) Lag screw b) Compression plate

56. a) Lag screw

57. b) Compression plate

58. Indirect fracture healing: • Under conditions of relative stability. • Callus formation occurs. • Occurs by secondary healing .

59. Indirect Bone Healing Mechanism for healing in fractures that have some motion, but not enough to disrupt the healing process. Bridging periosteal (soft) callus and medullary (hard) callus re-establish structural continuity Callus subsequently undergoes endochondral ossification Process fairly rapid - weeks

60. Indirect fracture healing

61. Examples of relative stability :

62. BIOCHEMICAL STEPS OF FRACTURE HEALING: Mesenchymal. Chondroid. Chondroid – osteoid. Osteogenic.

63. FACTORS INFLUENCING BONE HEALING: Mechanical factors. 2. Biological factors.

64. • Mechanical factors influencing bone healing: a) Soft tissue attachment to bone. b) Stability (extent of immobilization) c) Extent of bone loss. d) Level of energy impacted.

65. • Biological factors influencing bone healing : a) Age . b) Comorbidities associated. c) Nutrition status. d) Growth factors. e) Any associated vascular injury.

66. f) Type of bone affected. g) Local pathologic conditions. h) Smoking. Sterility. j) Soft tissue envelope.

67. GROWTH FACTORS OF BONE : Bone Morphogenic proteins (BMP) Transforming Growth Factor – beta ( TGF beta) Insulin-like Growth Factor (IGF-2) Platelet derived Growth Factor( PDGF) .

68. Hormones affecting fracture healing: Cortisone Calcitonin. Parathyroid Hormone ( PTH). Growth Hormone.

69. FACTORS PROMOTING BONE HEALING: •Therapy : a) Movement of the limb. b) Low intensity pulsed ultrasonography. •Local biological enhancement: a) Bone graft. b) Bone Morphogenic Proteins c) Growth factors.

70. •Systemic biological enhancement: a) PTH. b) Neuroproteins.

71. FACTORS IMPENDING BONE HEALING: During the soft callus phase, too much movement (excessive strain) risks tears in repaired tissue and compromises callus formation. This may cause delayed fracture healing or non-union.

72. REFERENCES CAMPBELL’S OPERATIVE ORTHOPEDICS ROCKWOOD AND GREEN ESSENTIAL ORTHOPEDICS-VARSHNEY

73. THANK YOU