3 - Principles of Bone Healing Flashcards

1
Q

Bone

A
  • A type of mineralized connective tissue , the blend made up of organic and inorganic components
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2
Q

Organic components of bone

A

Organic component (35% of bone)
o Cells = Osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts
o Matrix proteins
– 95% collagen type I (PRIMARY ORGANIC COMPONENT)
– 5% non-collagenous proteins (adhesion proteins, calcium binding proteins, mineralization proteins, enzymes, growth factors, etc.)

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3
Q

Inorganic component of bone

A
Inorganic  component (65% of bone)
o	Minerals (e.g. calcium hydroxyapatite)
o	Bone stores 95% of body’s calcium, 80% of phosphorus, and 65% of sodium and magnesium
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4
Q

Osteoid

A

Un-mineralized bone is called OSTEOID ***

o This is an immature form of organic matrix of bone which may be lined by osteoblasts

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5
Q

Osteoprogenitor cells

A

o Pluripotential mesenchymal cells which can mature to form osteoblasts

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6
Q

Osteoblasts

A

o Synthesize and transport protein (like type 1 collagen) and osteoprotegerin,
o Initiate mineralization
o Have receptors for parathyroid hormone, Vit. D and estrogen, cytokines
o Produce many growth factors (like Interleukin-1), and RANK-L (Receptor Activator of Nuclear factor-Kappa B) which combines with RANK receptor on osteoclasts to stimulate osteoclastic bone resorption
o Osteoblasts live on bone surfaces and surround woven bone
o Usually found in large groups (up to 400 cells) to form normal bone units
o Activity of osteoblasts is coordinated; become osteocytes when surrounded by matrix

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7
Q

Osteocytes

A

o Matured osteoblasts, found within the osseous matrix
o Regulate daily serum Ca++ and P
o Communication with other osteocytes via canaliculi
o Allow surface membrane potential and substrate transfer

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8
Q

Osteoclasts

A

o Responsible for bone resorption**
o Multiple nuclei
o Live in Howship lacunae
o Contain RANK receptors
* – can be blocked by osteoprotegerin

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9
Q

Osteoclast processes

A
  • Osteoclasts found on bone surface in small pits (Howship lacunae)
  • Responsible for bone resorption and initiate constant bone remodeling
  • Derived from hematopoietic progenitor cells → monocytes/macrophages; fuse into multinucleated giant cells, osteoclasts; contain many lysosomes rich in enzymes
  • Differentiation & maturation controlled by cytokines (NOT going to test cytokines)
  • Activity initiated by binding to surface matrix adhesion proteins
  • Do NOT resorb bone lined by osteoid or un-mineralized cartilage
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10
Q

Hormonal influences and receptors

NOT going to test the specifics of this

A
  • Estrogen ↑ (increases) bone formation by ↑ (increasing) collagen synthesis by osteoblasts
  • Estrogen prevents bone resorption by inhibiting osteoclast differentiation (osteoprotegerin)
  • Absence of estrogen (post-menopausal
    o Increased secretions of cytokines which stimulate osteoclasts and bone resorption
    o Decrease osteoprotegerin, which leads to further bone resorption
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11
Q

Microscopic organization of bone tissue

A
  • Type I collagen forms the backbone; 90% of protein
  • Collagen deposited in random weave (woven bone) or in parallel arrangement (lamellar bone)
  • Woven bone = normally present in fetal skeleton, at growth plates, and in processes where there is very rapid bone production; almost always pathologic in adults
  • Lamellar bone = gradually replaces woven bone during growth; stronger than woven bone; only type of normal bone in adults
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12
Q

Woven bone

A

IMMATURE BONE
- Haphazard arrangement (“random weave”) intermixed with fibrous tissue found in:
o Fetal skeleton and growth plates
o Callus (reparative bone, healing fracture)
o Fibrous dysplasia
o In areas surrounding tumor or infection
- Woven bone in adults always indicative of a pathologic state, but not diagnostic
- First type of bone laid down during growth and repair
o Grows rapidly, low strength, matures into lamellar bone

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13
Q

Lamellar bone

A

TRABECULAR BONE

  • Highly orderly, layered, strong, parallel arrangement of type I collagen with few osteocytes
  • Lamellae in compact bone are arranged concentrically around central vascular Haversian canals
  • Lamellae in cancellous bone are arranged in linear, parallel plates
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14
Q

Bone regions

A
  • Epiphysis = end of long bone
  • Epiphyseal plate = growth plate
  • Metaphysis = next to growth plate
  • Diaphysis = shaft
  • Periosteum = covering (blood vessels, nerves)
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15
Q

Cartilage components

A

No blood vessels, nerves or lymphatics

Inorganic phase
o Calcium hydroxyapatite crystals similar to bone

Organic matrix
o 80% water (↑ resilience & lubrication of joints), with remainder type II collagen and proteoglycans (chondroitin sulfates most abundant)

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16
Q

Bone modeling and remodeling

THIS IS IMPORTANT FOR HEALING

A
  • At maturity, breakdown and renewal of bone is equal –> it balances out
  • Beginning in the 4th decade, resorption begins to outweigh deposition
  • Rate of resorption is dependent on many factors:
    o Load on joints, age, nutrition, hormones (estrogen)
    o Calcium and Vitamin D intake, Vit. D receptor type
  • Bone will also do some remodeling depending on stress
  • The functional ‘basic multicellular’ unit is comprised of osteoblasts and osteoclasts
    o This tightly couples bone formation (modeling) and bone resorption and renewal (remodelling)
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17
Q

Control of bone resorption and bone formation

** NEED TO KNOW **

A
  • Here you can see osteoclasts breaking down bone
  • Surface osteoblasts become activated by 3 factors
    o Mechanical, hormones, cytokines
  • Activated osteoblasts start laying down osteoid
    o Collagen type I, which eventually becomes mineralized
    o This is the remodeling process
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18
Q

Bone remodeling cycle

A
  • Osteoclast precursors recruited to bone surface, where they fuse, differentiate, and mature.
  • Osteoclasts resorb both organic and inorganic bone matrix
  • Resorption phase ends with osteoclast apoptosis
  • In reversal phase, osteoblasts differentiate from mesenchymal precursors, under influence of factors from osteoclasts, and secrete new bone matrix (osteoid)
  • At the end of the cycle, some osteoblasts have been incorporated into bone as osteocytes and others remain on the surface as quiescent bone-lining cells
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19
Q

Cycle of bone turnover

KNOW THIS

A
  • Lining cells on bone become activated (mechanical/chemical)
  • Lining cells retract and the underlying membrane is removed by
    matrix metalloproteinases
  • Osteoclasts are then attracted to this cleared site, fuse then
    become activated
  • Osteoclast digestion of underlying bone occurs
  • Osteoblasts then move into the resorption cavity and form new
    osteoid, which is subsequently calcified
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20
Q

Cycle of bone turnover continued

KNOW THIS*

A
  • Not testing specific cytokines, but know that bone turnover
    occurs due to mechanical stress as well as systemic factors
    (endocrine, metabolic, nutritional)
  • Osteoclasts and osteoblasts act in a coordinated manner to
    form or resorb bone
  • Osteocytes act as mechanosensory cells and play a critical role
    in regulating bone remodeling
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21
Q

Vitamin C

A
  • Maintenance of normal connective tissue
  • Synthesizes collagen
  • Responsible for bone formation –> synthesizes organic matrix
  • Inorganic calcified portion of capillary walls
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22
Q

Vitamin C deficiency

A
  • Scurvy is a distinctive clinical syndrome related to problems with osteoid synthesis and collagen support of the blood vessels
  • In children, the osteoblasts lay down scanty, poor-quality osteoid
  • Radiographs and deformities similar to Rickets
  • In both children and adults, the capillaries weaken
  • Patients bruise easily, and bleed spontaneously, bleeding gums, petechiae around hair follicles
  • Bleeding into joints
  • Body hairs often become curled like “corkscrews”
  • Hemorrhages found around “corkscrew” hairs (perifollicular)
  • Hemorrhages beneath the periosteum develop
    o Subperiosteal hemorrhage
    o Most painful of the deficiency diseases
  • Wounds heal poorly and old ones reopen
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23
Q

Bone fractures

A

Fractures are 3,000-4,000 X more common than all primary bone tumors combined

24
Q

Types of bone fractures

A
  • Traumatic and non-traumatic (very common)
  • Stress fractures
  • Pathologic fractures
25
Q

Stress fracture

A

o Develop slowly following new strenuous repetitive activity

26
Q

Pathologic fractures

A

o Diseased bone; non-traumatic; may not repair if underlying disease is severe & prevents healing (e.g. severe osteoporosis; malignant tumor)

27
Q

Bone healing

A
  • Bone is generally able to repair through series of steps; completion of one initiating next through series of cellular interactions. Highly regulated.
28
Q

Causes of pathological fractures

A
Inherited and congenital diseases
o	Osteogenesis imperfecta
o	Osteopetrosis
o	Gaucher disease
o	Enchondromatosis
Metabolic bone disease and endocrine disturbances = MOST COMMON CAUSE
o	Hyperparathyroidism
o	Osteoporosis (generalized/localized)
o	Osteomalacia
o	Vitamin C deficiency 
o	Cushing disease, hyperthyroidism
o	Paget disease
Bone infection
o	Tumors and tumor-like conditions of bone (benign and malignant joint disease)
o	Ochronosis
o	Neuropathic joint
o	Rheumatoid arthritis
29
Q

Fracture healing

A

THIS IS WHAT YOU NEED TO KNOW

o Regulated by cytokines & growth factors

30
Q

3 stages of fracture healing

A

1 = Organization of hematoma at fracture site

2 = Conversion of procallus to fibrocartilaginous callus

3 = Replacement of mesenchymal cells by osseous callus

31
Q

Organization of hematoma at fracture site

A

Soft, organizing procallus(hematoma organizing by end of 1st week; anchorage, no structural rigidity)

32
Q

Conversion of procallus to fibrocartilaginous callus

A

Reactive mesenchymal cells (deposition of woven bone & new cartilage)
–> 3rd week – maximal enlargement

33
Q

Replacement of mesenchymal cells by osseous callus

A

Eventually remodeled along lines of WB; completes repair (endochondral ossification forms bony network; fractured ends bridged by bony callus)

34
Q

Fracture healing stages

A
  • Bleeding into site - HEMORRHAGE is the 1st step in healing
  • Organization of hematoma (procallus by end of 1st week)
  • Conversion of procallus into fibrocartilaginous callus (3rd week)
  • Replacement of mesenchymal cells by osseous callus; remodeling
35
Q

0-3 days post-fracture

A

Hemorrhage, fibrin inflammatory infiltrate, marrow necrosis, granulation tissue

36
Q

3-7 days post-fracture

A

Chronic inflammation (macrophages ++), granulation tissue, osteoclastic activity, early osteoid/woven bone formation by osteoblasts

37
Q

7-35 days post-fracture

A

Progressive increase in bone necrosis, chronic inflammation, reparative fibrous tissue, primary callus, woven bone and cartilage formation

38
Q

35+ days post-fracture

A

Secondary callus, replacement of woven by lamellar bone, osteoblastic and osteoclastic activity

39
Q

Image of bone callus

A
  • Orderly progression of cartilage into microtrabecular new bone
  • Primary callus will show formation of cartilage and woven bone
40
Q

Fracture healing inhibitory factors

*NEED TO KNOW THIS LIST

A
  • Infection
  • Non-union (malalignment, comminution)
  • Inadequate immobilization of fracture site
  • Poor circulation; poor nutrition (e.g. vitamin D or vitamin C deficiency)
  • Drugs (e.g. corticosteroids, immunosuppressives, cytotoxic therapy)
  • Underlying systemic abnormality (e.g. osteoporosis; hyperparathyroidism)
  • Overstressing healing fracture

NOTE - If fracture well-aligned & original weight-bearing strains restored, virtually perfect healing may occur; well aligned, incomplete, & closed heal most rapidly

41
Q

Avascular necrosis (AVN) (AKA osteonecrosis)

A
  • Infarction of bone and marrow resulting from ischemia

- Relatively common, most common site is the femoral head

42
Q

Mechanism of avascular necrosis

A

o Fracture (mechanical vascular interruption)*
o Corticosteroids
*
o Uncertain cause (idiopathic)***
o Thrombosis and embolism (e.g. sickle cell disease!)
o Vessel injury 2° to vasculitis, radiation therapy
o ↑ (high) intraosseous pressure with vascular compression
o Venous hypertension

*** = seen most frequently

43
Q

Osteomyeilitis

KNOW THIS - INFECTION

A

o Inflammation of bone and marrow caused by infection

o Most commonly by pyogenic agents or Mycobacterium tuberculosis

44
Q

Acute osteomyelitis

A

o Most acute purulent cases caused by bacteria

45
Q

Routes of aquiring osteomyelitis

A

o Hematogenous spread (most common)
o Direct extension from adjacent acute inflammation (abscess on foot spread to bone)
o From open fracture or surgical procedure

46
Q

Pyogenic osteomyelitis

A
  • In ½ of cases, no organism isolated; if organism is isolated, 80-90% Staph. Aureus***
  • Mixed infections are common
  • Other common pathogens: pneumococci, E. coli, group B strep. (most common in neonates)
  • Salmonella important cause in sickle cell patients***
47
Q

Osteomyelitis of spinal column (example)

A
  • Initial osteonecrosis has been followed by subperiosteal pyogenic abscesses
  • With healing, there will be deposition of reactive bone around the devitalized bone tissue
  • The process can be quite destructive, as seen in this example involving three vertebral bodies
48
Q

CHRONIC pyogenic osteomyelitis

A
  • Chronic osteomyelitis (10% of cases) → repair reaction: osteoclast activation, fibroblastic proliferation, and new bone formation
  • Sequestrum: residual necrotic bone; may be resorbed or (if larger) surrounded by rim of reactive bone called involucrum
49
Q

Outcomes of chronic pyogenic osteomyelitis

A

Chronic osteomyelitis may:
o Heal
o Drain into sinus tracts
o Be walled off to create a Brodie abscess

50
Q

Brodie abscess

A

 Brodie abscess: when well-defined rim of sclerotic bone surrounds residual abscess; viable organisms may persist

51
Q

Chronic osteomyelitis can lead to further patholgoy

A

o Pathologic fracture; endocarditis; sepsis; squamous cell carcinoma of sinus tract; rarely sarcoma and 2° amyloidosis

52
Q

Types of chronic osteomyelitis

A
  • Sequestrum = Inner necrotic cortex (the NECROTIC bone)
  • Involucrum = New woven bone surrounding drainage tract
  • Sinus tract = Very dangerous, drains out the skin or into the body, canal can develop squamous cell carcinoma or osteosarcoma (in older patients)
53
Q

Bone processing - decalcification

A

o The process of removing calcium from decalcified tissue and making suitable for section cutting (when you send a bone biopsy to pathology, it needs to be decalcified)
o In presence of calcium salts makes the tissue hard and brittle, which will cause difficulty in section cutting and damage to the microtome knife
o Decalcification takes 24-72 hours

54
Q

Decalcifying agents

A

o Nitric acid, Hydrochloric acid, Formic acid, Picric acid, Acetic acid, Citric acid
o Bouin’s solution is used for decalcifying bone biopsy samples - KNOW THIS

55
Q

Further processing of bone

A

o After decalcification, it needs to be fixed, undergo paraffin processing, embedded into paraffin blocks, stained, sectioned and viewed for signs of osteomyelitis or other pathology = this takes time***