DOW UNIVERSITY OF HEALTH SCIENCES

ASSIGNMENT

FRACTURE HEALING
SHAFAQ ZAHID ROLLNO 65 3RD YR 5TH SEMESTER

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 Lamellar bone Cortical bone - Comprised of osteons (Haversian systems) runs longitudinally Osteons communicate with medullary cavity by Volkmanns canals that run horizontally Haversian System

Woven Bone
Coarse with random orientation Weaker than lamellar bone

Normally remodeled to lamellar bone

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 Ca5(PO4)3(OH)2

Osteoblasts Derived from mesenchymal stem cells Line the surface of the bone and produce osteoid

 Immediate precursor is fibroblast-like preosteoblasts

Osteocytes Osteoblasts surrounded by bone matrix trapped in lacunae Function poorly understood regulating bone metabolism in response to stress and strain

Osteoclasts
Derived from hematopoietic stem cells (monocyte precursor cells) Multinucleated cells whose function is bone resorption Reside in bone resorption pits (Howships lacunae) Parathyroid hormone stimulates receptors on osteoblasts that activate osteoclastic bone resorption Components of Bone Formation Cortex

 Periosteum Bone marrow Soft tissue

FRACTURE
Fracture is a break in the structural continuity of bone . It may be a crack , a crumpling or a splintering of the cortex. TYPES OF FRACTURES
ON BASIS OF ETIOLOGY - Traumatic fracture - pathologic fractures due to some diseases - stress fracture ON BASIS OF DISPLACEMEMT - undisplaced - displaced translation ( shift ) angulation ( tilt ) rotation ( twist )

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

Prerequisites for Bone Healing

Adequate blood supply Adequate mechanical stability

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

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 HISTORY In 1975, Cruess and Dumont proposed that fracture healing may be considered to consist of three overlapping phases: an inflammatory phase, a reparative phase, and a remodeling phase In 1989, FROST proposed the stages of fracture healing five stages. stage of haematoma stage of granulation tissue stage of callus stage of modelling stage of remodelling 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

Inflammation
inflammatory phase is identical to the typical inflammatory response of most tissues to traumatic injury. Vasodilation and hyperemia, presumably mediated by histamines, prostaglandins, and various cytokines, accompany invasion of the injury site by neutrophils, basophils, and phagocytes that participate in clearing away necrotic debris. 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

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.

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.

 Hard callus formed at the periphery of the callus by intermembranous bone formation 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

Repair

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. 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

Types for Bone Healing

Direct (primary) bone healing Indirect (secondary) bone healing 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 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

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

VARIABLES THAT INFLUENCE THE FRACTURE HEALING

Systemic factors or patient variables Age Activity level including 1. immobilization . Nutritional status . Hormonal factors . Growth hormone . Corticosteroids . Others (thyroid, estrogen, androgen, calcitonin, parathyroid hormone, prostaglandins) . Cigarette smoking . Diseases: diabetes,anemia,neuropathies,

tabes dorsalis . Vitamin deficiencies: A, C, D, K . Drugs: nonsteroidal antiinflammatory drugs

(NSAIDs), anticoagulants, factor XIII, calcium channel blockers (verapamil), cytotoxins, diphosphonates, phenytoin (Dilantin), sodium fluoride, tetracycline . Other substances (nicotine, alcohol) . Hyperoxia . Systemic growth factors

. Environmental temperature . Central nervous system trauma

II. Local factors or tissue variables

. Factors independent of injury, treatment, or complications . Type of bone cortical or cancellous . Abnormal bone a. Radiation necrosis b. Infection c. Tumors and other pathological conditions 3. Denervation B. Factors depending on injury or injury variables 1. Degree of local damage a. Compound fracture b. Comminution of fracture c. segmental fractures d. Velocity of injury e. Low circulatory levels of vitamin K1 2. Extent of disruption of vascular supply to bone, its fragments (macrovascular osteonecrosis), or soft tissues; 3. Type and location of fracture (one or two bones, e.g., tibia and fibula or tibia alone 4. Loss of bone 5. Soft-tissue interposition 6. Local growth factors 7. Intraarticular fractures

Factors depending on treatment

1. Extent of surgical trauma (blood supply, heat) 2. Implant-induced altered blood flow 3. Degree and kind of rigidity of internal or external fixation and the influence of timing 4. Degree, duration, and direction of loadinduced deformation of bone and soft tissues 5. Apposition of fracture fragments (gap, displacement, overdistraction) 6. Factors stimulating posttraumatic osteogenesis (bone grafts, bone morphogenetic protein, electrical stimulation, surgical technique, intermittent venous stasis . D. Factors associated with complications 1. Infection 2. Venous 3. Metal allergy

Local Regulation of Bone Healing

Growth factors o Transforming growth factor o Bone morphogenetic proteins o Fibroblast growth factors o Platelet-derived growth factors o Insulin-like growth factors Cytokines Interleukin-1,-4,-6,-11, macrophage and granulocyte/macrophage (GM) colony-stimulating factors (CSFs) and Tumor Necrosis Factor Prostaglandins/Leukotrienes Hormones Growth factor antagonists

Summary
Fracture healing is influenced by many variables including mechanical stability, electrical environment, biochemical factors and blood flow Our ability to enhance fracture healing will increase as we better understand the interaction between these variables