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
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.)
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
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
5
Q
Osteoprogenitor cells
A
o Pluripotential mesenchymal cells which can mature to form osteoblasts
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
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
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
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
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
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
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
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
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)
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)
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)
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
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
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
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
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
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
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
Stress fracture
o Develop slowly following new strenuous repetitive activity
26
Pathologic fractures
o Diseased bone; non-traumatic; may not repair if underlying disease is severe & prevents healing (e.g. severe osteoporosis; malignant tumor)
27
Bone healing
- Bone is generally able to repair through series of steps; completion of one initiating next through series of cellular interactions. Highly regulated.
28
Causes of pathological fractures
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Inherited and congenital diseases
o Osteogenesis imperfecta
o Osteopetrosis
o Gaucher disease
o Enchondromatosis
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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
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Bone infection
o Tumors and tumor-like conditions of bone (benign and malignant joint disease)
o Ochronosis
o Neuropathic joint
o Rheumatoid arthritis
```
29
Fracture healing
THIS IS WHAT YOU NEED TO KNOW
| o Regulated by cytokines & growth factors
30
3 stages of fracture healing
1 = Organization of hematoma at fracture site
2 = Conversion of procallus to fibrocartilaginous callus
3 = Replacement of mesenchymal cells by osseous callus
31
Organization of hematoma at fracture site
Soft, organizing procallus(hematoma organizing by end of 1st week; anchorage, no structural rigidity)
32
Conversion of procallus to fibrocartilaginous callus
Reactive mesenchymal cells (deposition of woven bone & new cartilage)
--> 3rd week – maximal enlargement
33
Replacement of mesenchymal cells by osseous callus
Eventually remodeled along lines of WB; completes repair (endochondral ossification forms bony network; fractured ends bridged by bony callus)
34
Fracture healing stages
- 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
0-3 days post-fracture
Hemorrhage, fibrin inflammatory infiltrate, marrow necrosis, granulation tissue
36
3-7 days post-fracture
Chronic inflammation (macrophages ++), granulation tissue, osteoclastic activity, early osteoid/woven bone formation by osteoblasts
37
7-35 days post-fracture
Progressive increase in bone necrosis, chronic inflammation, reparative fibrous tissue, primary callus, woven bone and cartilage formation
38
35+ days post-fracture
Secondary callus, replacement of woven by lamellar bone, osteoblastic and osteoclastic activity
39
Image of bone callus
- Orderly progression of cartilage into microtrabecular new bone
- Primary callus will show formation of cartilage and woven bone
40
Fracture healing inhibitory factors
****NEED TO KNOW THIS LIST***
- 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
Avascular necrosis (AVN) (AKA osteonecrosis)
*****
- Infarction of bone and marrow resulting from ischemia
| - Relatively common, most common site is the femoral head
42
Mechanism of avascular necrosis
****
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
Osteomyeilitis
***KNOW THIS - INFECTION***
o Inflammation of bone and marrow caused by infection
| o Most commonly by pyogenic agents or Mycobacterium tuberculosis
44
Acute osteomyelitis
o Most acute purulent cases caused by bacteria
45
Routes of aquiring osteomyelitis
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
Pyogenic osteomyelitis
- 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
Osteomyelitis of spinal column (example)
- 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
CHRONIC pyogenic osteomyelitis
- 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
Outcomes of chronic pyogenic osteomyelitis
Chronic osteomyelitis may:
o Heal
o Drain into sinus tracts
o Be walled off to create a Brodie abscess
50
Brodie abscess
Brodie abscess: when well-defined rim of sclerotic bone surrounds residual abscess; viable organisms may persist
51
Chronic osteomyelitis can lead to further patholgoy
o Pathologic fracture; endocarditis; sepsis; squamous cell carcinoma of sinus tract; rarely sarcoma and 2° amyloidosis
52
Types of chronic osteomyelitis
- 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
Bone processing - decalcification
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
Decalcifying agents
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
Further processing of bone
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***
