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Manal Ismail Abd-Elghany
Associate Professor of Pathology, PhD (UK),
MD(Egypt)
Musculo-skeletal System Part I
Inflammatory Bone Diseases
& Bone Fracture Healing
Inflammatory Bone Diseases
Definition
 Infection of the bone & marrow is termed
osteomyelitis (myelo= marrow).
 Two conditions produce significant
pathologic lesions in the bone, namely:
A. Pyogenic osteomyelitis
B. Tuberculous osteomyelitis.
1
Osteomyelitis
Classification
A. Bacterial Osteomyelitis:
1. Acute osteomyelitis (Acute Suppurative Osteomyelitis)
a. Acute hematogenous osteomyelitis
b. Acute non- hematogenous osteomyelitis
2. Chronic osteomyelitis
a. Chronic specific osteomyelitis (e.g. TB, syphilis)
b. Chronic non-specific osteomyelitis
B. Non-bacterial Osteomyelitis:
1. Viral
2. Sarcoidosis
3. Radiation
2
Tuberculous Osteomyelitis
 Aetiology:
 It occurs due to blood borne infection
(systemic) by Mycobacterium tuberculosis
bacilli.
 Site:
 The lower thoracic and upper lumbar
vertebrae are commonly affected followed
by cervical vertebrae.
6
Tuberculosis of Vertebrae
(Pott’s disease)
 Pathological Features of Pott’s Disease:
 The tuberculous reaction involves the body
of the vertebrae & inter-vertebral disc which
results in their destruction and leads to
vertebral collapse and spinal deformity.
 The pathological features include:
◘ 1. Kyphosis:
◘ 2. Cold abscess formation:
◘ 3. Paraplegia:
◘ 4. Other complications: 4
1. Kyphosis: This spinal deformity occurs
due to forward or outward curvature of
destroyed vertebrae.
5
Kyphosis
(Spinal deformity due to vertebral destruction & collapse)
Kyphosis
Vertebral destruction
& collapse
Kyphosis
Vertebral
destruction
& collapse
2. Cold abscesses formation:
 Cold abscess refers to an abscess that lacks
the acute intense inflammation usually
associated with infection. It develops slowly
then takes the path of least resistance. It is
composed of squeezed caseous material.
6
Cold Abscess
Kyphosis
3. Paraplegia: This neurological disorder
occurs in about 10-30% of cases due to:
a) Compression of the spinal cord.
b) Ischemia (due to endarteritis).
c) Spinal cord trauma (due to bone
fracture).
4. Other complications of Pott’s disease:
a) Formation of Sinuses with dribbling of the
caseous material from the ruptured cold
abscess.
b) Secondary infection
c) Amyloidosis 7
Acute Hematogenous
Suppurative/Pyogenic
Osteomyelitis
1. The causative organism: In 80% of cases,
“Staphylococcus aureus”. Less commonly,
“Salmonella, E.coli, Pneumococci,
Streptococci & Staphylococcus albus”.
2. Source of infection: The microorganisms are
derived from infections anywhere in the body
e.g. respiratory, intestinal, urinary, oral, skin
….etc. This usually occurs following trivial
injury at site of infection, then the bacteria
enters the blood (i.e. bacteremia) and reach
the bone.
Etiology & pathogenesis
8
Etiology & Pathogenesis continued
3. Affected bones, location of infection
and age of patient:
 The most commonly affected bones by blood
spread are the long bones followed by
vertebrae.
 The location or site’ of lesion within the
affected bone depends on the vasculature
of this area as well as the age of the patient.
9
Etiology & Pathogenesis continued
 Infection occurs most commonly in the
metaphysis of long bones of infants and young
children (5-15 years of age), particularly in the
developing countries.
 The metaphysis is very rich in blood & the flow of
blood within it is slow, moreover it’s very liable to
trauma. Trauma ’s a very important predisposing
factor in this age group.
 In the developed countries, however, direct
extension of infection from the adjacent area is a
more common way of spread. Frequently
involving sites are the jaws & skull in adults.
10
 Bacterial osteomyelitis may be a
complication at all ages in patients
with:
 A. Compound fractures
 B. Surgical procedures involving prosthesis
or implants
 C. Gangrene of a limb
 D. Diabetes Mellitus
 E. Debilitation (very week) and immuno-
suppression
11
Etiology & Pathogenesis continued
1. The initial lesion is suppurative focus in
the metaphysis
Pathological features
12
 2. Spread of infection occurs by
penetrating the endosteum then reach the
haversian system through which the infection
reaches the periosteum and a sub-
periosteal abscess is formed i.e. beneath
the periosteum.
13
 3. Rupture of sub-periosteal abscess results in
formation of sinuses.
 4. Necrosis of bone occurs due to liquefactive
necrosis/absces (as a result of the pyogenic
infection) & ischemic necrosis (as a result of
thrombosis of periosteal vessels).
 5. Separation of the necrotic bone by osteoclasts.
The separated part is called “sequestrum”.
14
6. The periosteum shows gradual thickening
due to new bone formation which is called
“involucrum”.
7. The sinuses now appear thick-walled holes
and are called “cloacae”.
15
Summary of Pathological features of
Acute Hematogenous Pyogenic Osteomyelitis
 1. Initial suppurative focus in the metaphysis.
 2. Sub-periosteal abscess formation.
 3. Sinuses formation as a result of rupture of
sub-periosteal abscess.
 4. Necrosis of bone.
 5. Sequestrum: is the separated dead bone.
 6. Involucrum: thickened periosteum due to
new bone formation.
 7. Cloacae: thick-walled sinuses.
1. Direct extension or spread of infection
causing arthritis, myositis and neuritis
2. Blood spread of infection causing
toxaemia and pyaemia
3. Chronic suppurative osteomyelitis which
may be further complicated by:
 2ry amyloidosis
 Epithelization of the sinuses which may later on
give rise to squamous cell carcinoma
4. Pathological fracture
Complications
16
Repair of Bone Fracture
 In a few special situations when the two ends of
the fracture are approximated, "primary union"
occurs. It involves a direct attempt of the cortex
to re-establish itself after interruption, without
formation of callus. Just like in skin wound,
primary healing occurs when the edges are
closely approximated.
 More commonly, "secondary union" occurs in
the process of healing of bone fracture.
 “A pathologic fracture” occurs when a bone
breaks in an area that was already weakened
by some underlying medical condition.
Introduction
17
Causes of Pathological Bone Fracture
1) Inflammatory diseases (e.g. acute &
chronic osteomyelitis)
2) Osteodystrophies*: e.g. osteoporosis,
Osteitis Fibrosa Cystica , rickets,
fibrous dysplasia & Paget’s disease
3) Primary malignant tumours arising
from bones
4) Metastasis to bones (i.e. secondary)
5) Bone cysts
* N.B. For further information regarding the terminology of these diseases, please see
the last slide. 18
Mechanism of Secondary Bone Union
1. Haematoma (blood clot) formation
2. Local inflammatory response:
 It occurs at the site of injury with formation of cellular &
fluid exudates.
 Phagocytosis of products
of inflammation occurs by
macrophages.
 Removal of bone
fragments occurs by
means of osteoclasts.
19
3. Granulation tissue (soft callus) formation:
 The hematoma is replaced gradually by
granulation tissue. The organized hematoma is
called soft callus.
 N.B. Granulation tissue:
It consists of many newly-
formed capillaries,
proliferated fibroblasts &
collagen type III.
 N.B. Callus: Any tissue
that unites the two ends of
the fracture is known as
callus.
 Hematoma is replaced gradually by
Granulation tissue which is called soft callus.
 N.B. Healing by organization means
formation of Granulation tissue.
Organized
20
4. Transformation of soft callus into
“Fibro-cartilaginous callus”:
 At this stage, the callus is formed of :
A. Fibrous tissue
B. Cartilage
C. Woven bone
or immature
non-lamellar bone.
21
5. Formation of Bony Callus:
A. Osteoclastic activity occurs to remove degenerated
cartilage.
B. This is accompanied
by osteoblastic activity
i.e. further deposition
of osteoid tissue with
progressive calcification.
C. Finally bony callus
is formed which is
formed of lamellar mature
hard bone.
22
Formation of Bony Callus
(hard, lamellar or mature callus)
1
2
3
External callus
Intermediate callus
Internal callus
6. Callus Remodeling:
a) Removal of external + internal callus
by osteoclasts.
b) Further adjustment of intermediate
callus (in response to mechanical
stress along lines of weight
bearing).
23
External callus
Intermediate
callus
Internal callus
Summary of Mechanism of Secondary Bone Union
1.Hematoma then
granulation tissue
formation or soft
callus
2. Fibro-
cartilaginous
callus
3. Bony callus 4. Remodeling
Complications of Fracture Healing
 Bony union may fail to occur due to:
1. Continuous movement which leads to
fibrous union.
2. Infection at the site of fracture.
3. Impairment of blood supply.
4. Interposition of some soft tissue between
the fractured ends.
5. Nutritional disturbances and old age.
24
N.B. Terminology “Only for reading and it’s not a part from the lecture”
 Osteoporosis
 Osteoporosis is a common clinical syndrome involving multiple bones in which
there is quantitative reduction of bone tissue mass but the bone tissue mass
is otherwise normal.
 Rickets
 A disease affecting children which is characterized by defective mineralization
of bone.
 Osteitis Fibrosa Cystica
 Hyperparathyroidism of primary or secondary type results in over secretion of
parathyroid hormone, which causes increased osteoclastic resorption of the
bone.
 Paget's disease of bone
 It is an osteolytic and osteosclerotic bone disease of uncertain etiology
involving one or more bones.
 Fibrous Dysplasia
 It is a benign condition, possibly of developmental origin.
 It is characterized by the presence of localized area in which there is
replacement of bone by fibrous connective tissue with a characteristic whorled
pattern and containing trabeculae of woven bone.

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Inflammatory bone diseases & bone fracture_Dr.Manal Ismail Abd-Elghany_2022.pptx

  • 1. Manal Ismail Abd-Elghany Associate Professor of Pathology, PhD (UK), MD(Egypt) Musculo-skeletal System Part I Inflammatory Bone Diseases & Bone Fracture Healing
  • 3. Definition  Infection of the bone & marrow is termed osteomyelitis (myelo= marrow).  Two conditions produce significant pathologic lesions in the bone, namely: A. Pyogenic osteomyelitis B. Tuberculous osteomyelitis. 1 Osteomyelitis
  • 4. Classification A. Bacterial Osteomyelitis: 1. Acute osteomyelitis (Acute Suppurative Osteomyelitis) a. Acute hematogenous osteomyelitis b. Acute non- hematogenous osteomyelitis 2. Chronic osteomyelitis a. Chronic specific osteomyelitis (e.g. TB, syphilis) b. Chronic non-specific osteomyelitis B. Non-bacterial Osteomyelitis: 1. Viral 2. Sarcoidosis 3. Radiation 2
  • 6.  Aetiology:  It occurs due to blood borne infection (systemic) by Mycobacterium tuberculosis bacilli.  Site:  The lower thoracic and upper lumbar vertebrae are commonly affected followed by cervical vertebrae. 6 Tuberculosis of Vertebrae (Pott’s disease)
  • 7.  Pathological Features of Pott’s Disease:  The tuberculous reaction involves the body of the vertebrae & inter-vertebral disc which results in their destruction and leads to vertebral collapse and spinal deformity.  The pathological features include: ◘ 1. Kyphosis: ◘ 2. Cold abscess formation: ◘ 3. Paraplegia: ◘ 4. Other complications: 4
  • 8. 1. Kyphosis: This spinal deformity occurs due to forward or outward curvature of destroyed vertebrae. 5
  • 9. Kyphosis (Spinal deformity due to vertebral destruction & collapse) Kyphosis Vertebral destruction & collapse
  • 11. 2. Cold abscesses formation:  Cold abscess refers to an abscess that lacks the acute intense inflammation usually associated with infection. It develops slowly then takes the path of least resistance. It is composed of squeezed caseous material. 6 Cold Abscess Kyphosis
  • 12. 3. Paraplegia: This neurological disorder occurs in about 10-30% of cases due to: a) Compression of the spinal cord. b) Ischemia (due to endarteritis). c) Spinal cord trauma (due to bone fracture). 4. Other complications of Pott’s disease: a) Formation of Sinuses with dribbling of the caseous material from the ruptured cold abscess. b) Secondary infection c) Amyloidosis 7
  • 14. 1. The causative organism: In 80% of cases, “Staphylococcus aureus”. Less commonly, “Salmonella, E.coli, Pneumococci, Streptococci & Staphylococcus albus”. 2. Source of infection: The microorganisms are derived from infections anywhere in the body e.g. respiratory, intestinal, urinary, oral, skin ….etc. This usually occurs following trivial injury at site of infection, then the bacteria enters the blood (i.e. bacteremia) and reach the bone. Etiology & pathogenesis 8
  • 15. Etiology & Pathogenesis continued 3. Affected bones, location of infection and age of patient:  The most commonly affected bones by blood spread are the long bones followed by vertebrae.  The location or site’ of lesion within the affected bone depends on the vasculature of this area as well as the age of the patient. 9
  • 16. Etiology & Pathogenesis continued  Infection occurs most commonly in the metaphysis of long bones of infants and young children (5-15 years of age), particularly in the developing countries.  The metaphysis is very rich in blood & the flow of blood within it is slow, moreover it’s very liable to trauma. Trauma ’s a very important predisposing factor in this age group.  In the developed countries, however, direct extension of infection from the adjacent area is a more common way of spread. Frequently involving sites are the jaws & skull in adults. 10
  • 17.  Bacterial osteomyelitis may be a complication at all ages in patients with:  A. Compound fractures  B. Surgical procedures involving prosthesis or implants  C. Gangrene of a limb  D. Diabetes Mellitus  E. Debilitation (very week) and immuno- suppression 11 Etiology & Pathogenesis continued
  • 18. 1. The initial lesion is suppurative focus in the metaphysis Pathological features 12
  • 19.  2. Spread of infection occurs by penetrating the endosteum then reach the haversian system through which the infection reaches the periosteum and a sub- periosteal abscess is formed i.e. beneath the periosteum. 13
  • 20.  3. Rupture of sub-periosteal abscess results in formation of sinuses.  4. Necrosis of bone occurs due to liquefactive necrosis/absces (as a result of the pyogenic infection) & ischemic necrosis (as a result of thrombosis of periosteal vessels).  5. Separation of the necrotic bone by osteoclasts. The separated part is called “sequestrum”. 14
  • 21. 6. The periosteum shows gradual thickening due to new bone formation which is called “involucrum”. 7. The sinuses now appear thick-walled holes and are called “cloacae”. 15
  • 22. Summary of Pathological features of Acute Hematogenous Pyogenic Osteomyelitis  1. Initial suppurative focus in the metaphysis.  2. Sub-periosteal abscess formation.  3. Sinuses formation as a result of rupture of sub-periosteal abscess.  4. Necrosis of bone.  5. Sequestrum: is the separated dead bone.  6. Involucrum: thickened periosteum due to new bone formation.  7. Cloacae: thick-walled sinuses.
  • 23. 1. Direct extension or spread of infection causing arthritis, myositis and neuritis 2. Blood spread of infection causing toxaemia and pyaemia 3. Chronic suppurative osteomyelitis which may be further complicated by:  2ry amyloidosis  Epithelization of the sinuses which may later on give rise to squamous cell carcinoma 4. Pathological fracture Complications 16
  • 24. Repair of Bone Fracture
  • 25.  In a few special situations when the two ends of the fracture are approximated, "primary union" occurs. It involves a direct attempt of the cortex to re-establish itself after interruption, without formation of callus. Just like in skin wound, primary healing occurs when the edges are closely approximated.  More commonly, "secondary union" occurs in the process of healing of bone fracture.  “A pathologic fracture” occurs when a bone breaks in an area that was already weakened by some underlying medical condition. Introduction 17
  • 26. Causes of Pathological Bone Fracture 1) Inflammatory diseases (e.g. acute & chronic osteomyelitis) 2) Osteodystrophies*: e.g. osteoporosis, Osteitis Fibrosa Cystica , rickets, fibrous dysplasia & Paget’s disease 3) Primary malignant tumours arising from bones 4) Metastasis to bones (i.e. secondary) 5) Bone cysts * N.B. For further information regarding the terminology of these diseases, please see the last slide. 18
  • 27. Mechanism of Secondary Bone Union 1. Haematoma (blood clot) formation 2. Local inflammatory response:  It occurs at the site of injury with formation of cellular & fluid exudates.  Phagocytosis of products of inflammation occurs by macrophages.  Removal of bone fragments occurs by means of osteoclasts. 19
  • 28. 3. Granulation tissue (soft callus) formation:  The hematoma is replaced gradually by granulation tissue. The organized hematoma is called soft callus.  N.B. Granulation tissue: It consists of many newly- formed capillaries, proliferated fibroblasts & collagen type III.  N.B. Callus: Any tissue that unites the two ends of the fracture is known as callus.  Hematoma is replaced gradually by Granulation tissue which is called soft callus.  N.B. Healing by organization means formation of Granulation tissue. Organized 20
  • 29. 4. Transformation of soft callus into “Fibro-cartilaginous callus”:  At this stage, the callus is formed of : A. Fibrous tissue B. Cartilage C. Woven bone or immature non-lamellar bone. 21
  • 30. 5. Formation of Bony Callus: A. Osteoclastic activity occurs to remove degenerated cartilage. B. This is accompanied by osteoblastic activity i.e. further deposition of osteoid tissue with progressive calcification. C. Finally bony callus is formed which is formed of lamellar mature hard bone. 22 Formation of Bony Callus (hard, lamellar or mature callus) 1 2 3 External callus Intermediate callus Internal callus
  • 31. 6. Callus Remodeling: a) Removal of external + internal callus by osteoclasts. b) Further adjustment of intermediate callus (in response to mechanical stress along lines of weight bearing). 23 External callus Intermediate callus Internal callus
  • 32. Summary of Mechanism of Secondary Bone Union
  • 33. 1.Hematoma then granulation tissue formation or soft callus 2. Fibro- cartilaginous callus 3. Bony callus 4. Remodeling
  • 34. Complications of Fracture Healing  Bony union may fail to occur due to: 1. Continuous movement which leads to fibrous union. 2. Infection at the site of fracture. 3. Impairment of blood supply. 4. Interposition of some soft tissue between the fractured ends. 5. Nutritional disturbances and old age. 24
  • 35.
  • 36. N.B. Terminology “Only for reading and it’s not a part from the lecture”  Osteoporosis  Osteoporosis is a common clinical syndrome involving multiple bones in which there is quantitative reduction of bone tissue mass but the bone tissue mass is otherwise normal.  Rickets  A disease affecting children which is characterized by defective mineralization of bone.  Osteitis Fibrosa Cystica  Hyperparathyroidism of primary or secondary type results in over secretion of parathyroid hormone, which causes increased osteoclastic resorption of the bone.  Paget's disease of bone  It is an osteolytic and osteosclerotic bone disease of uncertain etiology involving one or more bones.  Fibrous Dysplasia  It is a benign condition, possibly of developmental origin.  It is characterized by the presence of localized area in which there is replacement of bone by fibrous connective tissue with a characteristic whorled pattern and containing trabeculae of woven bone.