Musculoskeletal system

2. Lecture 1
Congenital bone and Cartilage Diseases

3.  Musculoskeletal system pathology is
classified to :
 1- Pathology of Bone .
 2- Pathology of Cartilage and Joints .
 3- Pathology of Muscles .
 4- Pathology of Soft Tissues .

4.  Bone Pathology is classified to :
 1- Congenital .
 2- Acquired ( Metabolic , traumatic and
inflammatory ) .
 3- Neoplastic .

6. OSTEOGENIC IMPERFECTA

7. OSTEOGENESIS IMPERFECTA “Brittle
Bone Disease”
Definition: Hereditary conditions.
characterized by defective synthesis of type I collagen,
resulting in
defective bone matrix and brittle bone.
Manifestation: Mainly skeletal fragility, but joints, eyes, ears,
skin and teeth are involved because they are rich in type I
collagen.
Pathogenesis: Genetic defects resulting in mutations of
genes
coding alpha-1 and alpha-2 chains of the collagen.
The mutations inherited as autosomal dominant. Autosomal
recessive forms are not common.

8. OSTEOGENESIS IMPERFEC cont…
Morphology:
*The basic abnormality in all forms is too
little bone.
*Marked cortical thinning and attenuation
of
trabeculae.

9. Table 27-2. OSTEOGENESIS IMPERFECTA
SUBTYPE INHERITANCE COLLAGEN
DEFECT
MAJOR CLINICAL
FEATURES
OI I Postnatal
fractures,
blue sclerae
Autosomal
dominant
Decreased synthesis
pro-α 1(1) chain
Abnormal pro- α
1(1) or pro-α 1(2)
chains
Compatible with survival
Normal stature
Skeletal fragility
Dentinogenesis imperfecta
Hearing impairment
Joint laxity
Blue sclerae
OI II Perinatal
lethal
Most autosomal
recessive
Some autosomal
dominant
? New mutations
Abnormally short
pro-α 1(1) chain
Unstable triple helix
Abnormal or
insufficient pro-
α2 (1)
Death in utero or within
days of birth
Skeletal deformity with
excessive fragility and
multiple fractures
Blue sclerae

10. Osteogenesis Imperfecta

11. Type I OI- Mildest, most
common
Type II OI- Most severe
Type III OI- Moderate to severe
Type IV OI- Moderate
Type V- Moderate in severity
Type VI- Moderate

12. Osteogenesis imperfecta Type I
Very wide range of joint mobility due to
defective synthesis of collagen type I

14. Fibrous Dysplasia
 Fibrous dysplasia is a benign tumor-like lesion of
bone.
 It is best characterized as a localized
developmental arrest; all of the components of
normal bone are present, but they do not
differentiate into their mature structures.
 The normal trabecular bone is replaced by
proliferating fibrous tissue and disorderly islands of
malformed bone.

15. FIBROUS DYSPLASIA cont…….
Three forms
1. Involving a single bone (monostotic fibrous
dysplasia) 70% of all cases .
2. Involving multiple, but not all, bones (polyostotic
fibrous dysplasia) 27% of all cases .
3. 3% of all cases Polyostotic disease with
cafeau-lait skin pigmentation and endocrine
abnormalities especially precocious puberty .
Clinical course.
Monostotic diseased patients have minimal
symptoms . Polystotic patients suffer from
recurring fractures, deformities and rarely
malignant transformation of a lesion into
sarcoma such as osteosarcoma .

16. Fibrous Dysplasia
 Gross:
 the lesions are well circumscribed,
 They are intramedullary, and vary greatly in size,
larger lesions expand and distort the bone.
 The lesional tissue is tan-white and gritty.
 Microscopic:
 It is composed proliferation. of trabeculae of
woven bone surrounded by a moderately
cellular fibroblastic
 The shapes of the trabeculae mimic Chinese
letters, and the bone lacks osteoblastic rimming.
 Cystic degeneration, hemorrhage, and foamy
macrophages are other common findings.

17. Fibrous Dysplasia

19. Achondroplasia
 Achondroplasia is an inherited
disorder characterised by impaired
maturation of cartilage of growth
plate.
 It is a major cause of dwarfism and is
the most common disease of the
growth plate.
 Achondroplasia is an autosomal
dominant disorder, with approximately
80% of the cases representing new
mutations.

20. Achondroplasia
 Patients with this disorder have a point
mutation in the gene that codes for
fibroblast growth factor receptor 3
(FGFR3), located on chromosome 4.
 In the normal growth plate, activation
of FGFR3 inhibits cartilage
proliferation, and in achondroplasia
the mutation causes the receptor to
be in the state of constant activation.

21. Achondroplasia (cont.)
 The affected infant has
 shortened proximal extremities
 a trunk of relative normal length
 an enlarged head with bulging
forehead and conspicuous depression
of the root of the nose.
 The skeletal abnormalities are
usually not associated with
changes in longevity, intelligence,
or reproductive status.

22. Achondroplasia

24. Osteopetrosis(Marble Bone
Disease)
 This is a group of uncommon hereditary
disorders characterised by defect in osteoclast
activity with resultant increase in bone mass
(“marble bones”).
 The most common variants are the autosomal
recessive malignant type and the autosomal
dominant benign type .
 Despite increased bone mass, the bone is
abnormally brittle and fractures easily like a
piece of chalk. Patients suffers also from
anemia(due to lack of bone marrow) and
cranial nerve problems(due to small neural
foramina). May be treated by bone marrow
transplantation)

25. Osteopetrosis(Marble Bone
Disease) the bones lack a medullary
canal and the ends of the long bones are
bulbous and misshapen

26. OSTEOPETROSIS
Diffusely DENSE bone with Erlenmeyer Flask deformity of
distal humerus

28. Assessment
The main defect in Osteogenesis imperfecta is in:
•A- Osteoclasts
•B- Collagen synthesis
•C- Cartilagenous ossification
•D- Metaphyseal growth

30. Lecture 2
Endocrinal and
metabolic bone diseases

31. OSTEOPOROSIS 31
Bone with
Osteoporosis
Normal
Bone
Osteoporosis causes weak
bones. In this common
disease, bone become
fragile and break easily.

32. OSTEOPOROSIS
Definition:
Is a disorder characterized by reduction of bone
mass resulting in increased porosity.
The structural changes predispose to bone fragility
and fractures.
Divided :
- Localized (as in disuse osteoporosis, in
immobilized
extremity).
- Generalized involving entire skeletal system.

33. OSTEOPOROSIS cont…
Generalized osteoporosis
 primary (senile and postmenopausal
forms). The term osteoporosis it refers to
either senile or postmenopausal
osteoporosis.
 Secondary to a wide range of conditions.
Primary osteoporosis
 Senile osteoporosis occurs in adults of
both sexes and increases in severity with
age.
 Postmenopausal osteoporosis occurs in
women after menopause, causes
fractures in older women.

34. •amyloidosis
•use of glucocorticoids
•Iatrogenic osteoporosis caused
by the therapeutic drugs
•Alcohol
Rheumatologic disorders
•rheumatoid arthritis,
•ankylosing spondylitis
•Marfan syndrome
•hemochromatosis
•Hypophosphatasia
•epidermolysis bullosa
Secondary Osteoporosis
•homocystinuria
•porphyria
•Menkes' syndrome
INHERITED DISORDERS
OTHER DISORDERS
•immobilization,
•pregnancy and lactation
•scoliosis
•chronic obstructive
pulmonary disease
•osteogenesis imperfecta
•Ehlers-Danlos syndrome
•glycogen storage diseases

35. Hypogonadal states
•Turner syndrome,
•Klinefelter syndrome,
•Kallmann Syndrome,
•anorexia nervosa,
•hypothalamic amenorrhea,
•hyperprolactinemia.
Nutritional and gastrointestinal
disorders
•malnutrition,
•parenteral nutrition,
•malabsorption syndromes,
•gastrectomy,
• severe liver disease
(especially biliary cirrhosis),
•pernicious anemia.
•Vitamin C, D deficiency
Hematologic
disorders/malignancy
•multiple myeloma,
•lymphoma and
leukemia,
•mastocytosis,
•hemophilia,
•thalassemia.
Endocrine disorders
•Cushing's syndrome,
•hyperparathyroidism
• thyrotoxicosis,
•insulin-dependent
diabetes mellitus,
•acromegaly,
•adrenal insufficiency

37. Factors Contributing in the
Development of Osteoporosis
1. Age cause changes in bone density in all individuals in
both sexes.
Maximum bone density is reached by age 30y,
gradually decrease, 0.7% of bone lost yearly.
The rates of loss vary from one bone to another
(> loss spine and femoral necks, sites of fractures).
Age results in decrease in osteoblastic activity.
Bone remodel, with bone resorption and new bone
formation.
with each remodeling cycle, new bone formation does
not compensate for bone loss, resulting in gradual
attrition of bones.
This form is known as senile osteoporosis.

38. Factors Contributing in the
cont…
2. Hormonal factors
-Administration of estrogen to postmenopausal
women
reduces bone loss and fractures.
-Estrogen deficiency result in increase cytokines
production (IL -1,6 TNF-a) which
stimulates osteoclast recruitment and activity,
causing bone loss by increasing bone resorption
as
well as by decreasing bone synthesis.

39. Factors Contributing in the
cont…
In postmenopause
women have 2% reduction cortical bone and 9%
loss of cancellous bone.
Woman lose up to 35% of their cortical bone and
50%
of their trabecular bone within 30-40 years after
menopause.
1 out 2 women have osteoporotic fracture.
1 in 4o men has osteoporotic fracture.

40. Factors Contributing in the
cont
3. Genetic factors
-The maximum bone density of individual is
determined by genetic influences.
- The inherited type of vitamin D receptors (VDR)
determine 75% of the maximum bone mass
achieved.

41. Factors Contributing in the
cont
4. Mechanical factors
 weight bearing
 Are important stimuli for normal remodeling of bone,
 Reduced physical activity is associated with
accelerated bone loss, example immobilized
extremities.
 Sedentary life style contributes to osteoporosis.
 Higher bone density in athletes as compared with non-
Athletes.

42. Factors Contributing in the
cont…
5. Diet, calcium and Vitamin D intake,
Person’s maximum bone density is determined in
part by the total dietary calcium intake, before
puberty.

43. OSTEOPOROSIS
MORPHOLOGY
 The hallmark of osteoporosis is a loss of bone, the
entire skeleton is affected in postmenopausal and
senile osteoporosis.
In post-menopausal osteoprosis
 the cancellous bone of the vertebral bodies are
more affected. The osteoporotic trabeculae are
thinned and lose their interconnections, leading to
micro-fractures and vertebral collapse.
In senile osteoporosis
 the osteoporotic cortex is thinned by resorption
and haversion system are widened and enlarged
to mimic cancellous bone. The mineral content of
bone is normal, no alteration in the ratio of
minerals to protein matrix.

44. Osteoporosis
Morphology
 Osteoporotic vertebral body (right) shortened by
compression fractures compared by normal
vertebral body . There is characteristic loss of
horizontal trabeculae and thickened vertical
trabeculae .

45. The bone in these vertebral bodies demonstrates marked osteoporosis with
thinning and loss of bony trabeculae. The second body from the right shows
a greater degree of compression than the others. Osteoporosis is accelerated
bone loss with age and is particularly common amongst postmenopausal
women, putting them at risk for fractures (hip, wrist, vertebrae).

47. Osteoporosis Diagnosis
• In early stage osteoporosis is asymptomatic, it is
often called the "silent disease“.
• Osteoporosis cannot be reliably detected in plain
radiographs until 30% to 40% of the bone mass is
lost, and measurement of blood levels of calcium,
phosphorus, and alkaline phosphatase are not
diagnostic.
• Reliable diagnosis in early cases requires
radiographic measurement of bone density

48. Prevention of Osteoporosis
 Building strong bones, especially before the age
of 30, can be the best defense against
developing osteoporosis.
 There are several steps you can take to prevent
osteoporosis:
 Osteoporosis is largely preventable for most people.
 Prevention of this disease is very important because,
while there are treatments for osteoporosis, there is no
complete cure.
 There are four steps to prevent osteoporosis:
 A balanced diet rich in calcium and vitamin D
 Weight-bearing exercise
 A healthy lifestyle with no smoking or alcohol use
 And bone density testing and medications when
appropriate

49. Osteoporosis Complications
 Vertebral fractures that frequently occur in the
thoracic and lumbar regions are painful since it
cause neural compression.
 Multiple-level vertebral fractures can cause
significant loss of height and various deformities,
including lumbar lordosis and kyphoscoliosis.
 Complications of fractures of the femoral neck,
pelvis, or spine include pulmonary embolism and
pneumonia.

51. Deficiency states of Vitamin D
In adults result in OSTEOMALACIA.
It impairs or block the normal mineralization of
osteoid laid down in the remodeling of bone.
In children result in RICKETS.
It cause inadequate mineralizatioin of osteoid, and
it also result in inadequate provisional
mineralization of epiphyseal cartilage.

52. Causes of Rickets &
Osteomalacia
1. Dietary deficiencies (not in developed
countries).
2. Limited exposure to sunlight .
3. Deranged Vitamin D absorption.
4. Deranged Vitamin D metabolism.
5. Disorder affecting the function of
Vitamin D.
6. Disturb calcium or phosphorous hemostasis.

53. RICKETS
1. The basic defect is excess of unmineralized
bone.
2. Inadequate provisional calcification of
epiphyseal cartilage (abnormal
endochondral ossification).

54. RICKETS cont…
Clinical Manifestation
•In non ambulatory stage of infant has
– Skull:
• soft, flat occipital bone
• frontal bossing and squared head appearance
– Chest:
• enlarged costochondral junction (rachitic rosary)
• inward pulling of ribs and anterior protrusion of the
sternum (pigeon breast deformity)
– Pelvis:
• deformed pelvis
•In ambulating child has
– deformity of the spine, pelvis, and long bone (tibia).
– lumbar lordosis, deformed chest wall and bowing of
the legs

57. OSTEOMALACIA
1. The basic pathology is excess of
unmineralized matrix.
2. There is loss of skeletal mass or too
little bone or OSTEOPENIA resulting
from osteomalacia.

58. OSTEOMALACIA cont…
Morphology
• The bone contours are not affected, but the
bone is weak.
• gross fractures or microfractures are common,
and affect mainly vertebrae, hips, wrists and
ribs.
Histology
Osteomalacia is seen as thickened layer of matrix
pink on H & E arranged about the more basophilic
normally mineralized trabeculae.

59. OSTEOMALACIA cont…
Clinically:
Pathognomonic diagnostic feature for both rickets
and osteomalacia is looser’s zones or milkman’s
pseudo-fractures (radiological ).

61. Bone Diseases Associated
with Hyperparathyroidism
Hyperparathyroidism
Classified
1. Primary and results from autonomous
hyperplasia of the parathyroid glands, or
from tumor mostly adenoma of the gland.
2. Secondary results from prolonged
hypocalcemia (e.g. in chronic renal disease)
resulting in parathyroid hyperplasia and
hypersecration of parathyroid hormone.

62. Hyperparathyroidism
Morphology
The hallmark of PTH excess …….is increased
osteoclastic activity, with bone resorption.
• Bone resorption is pronounced in the
subperiosteal regions produce thinned cortices
and loss of lamina dura around the teeth.
• The entire skeleton is affected .
• The decrease in bone mass predispose to
fractures .

63. Hyperparathyroidism
Microscopically
• Excessive osteoclastic activity, erosion of bone
surfaces.
• Loose fibrovascular tissue in marrow spaces.
• Hemosiderin deposition, from hemorrhage due
to fractures.
• Osteocytes and fibroblasts form a mass, termed
a “brown tumor” of hyperparathyroidism.
• Cystic change is common.
• The osteoclastic activity, peritrabecular fibrosis,
and cystic brown tumor is known as osteitis
fibrosa cystica (Von Recklinghausen’s disease of
bone).

64. PRIMARY
HYPERPARATHYROIDISM
OSTEITIS FIBROSA CYSTICA “BROWN” “TUMOR”

65. Here is a "brown tumor" of bone in a patient with hyperpara-
thyroidism. The high parathormone levels increase osteoclast
activity and produce irregular bone resorption with
microfractures and hemorrhage and macrophage proliferation
and fibrous connective tissue proliferation.

66. Assessment
• The condition characterized by
decreased bone mass due to
increased bone resorption and/or
decreased bone deposition is
called:
A. Osteomyelitis
B. Multiple exostosis
C.Osteoporosis
D. Osteopetrosis

68. Lecture 3
Traumatic and Miscellaneous
diseases

69. FRACTURES, adjectives
 The most common pathologic conditions affecting bone are
Fractures & classified to:
 Complete, incomplete
 Closed, open (communicating)
 Comminuted (splintered)
 Displaced (NON-aligned)
 Pathologic, (non-traumatic, secondary to
other disease, often metastases)
 “STRESS” fracture

70. Fractures
Healing of a fracture depend on:
 Type of fracture
 If the fractured bone was previously normal or
diseased (pathological fracture occur at sites of
metastatic tumors).
Incomplete Complete Displaced
(green stick) The ends of
fractured bone not
aligned
Closed Comminute Compound
Simple intact Splintered Fracture site
Skin bone Communict with
skin

71. Fractures cont….:
 Incomplete closed fracture heals rapidly
with complete reconstruction of the normal
bone.
 Comminuted, compound heal slowly and
can have poor end result.
 Stress fracture develop slowly caused by
increased physical activity as in sports
training.

72. Healing
is a continous process – 3 stages:
 Organization of hematoma which result in soft
organizing procallus.
 Conversion of the procallus to
fibrocartilagenous callus which give effective
immobilization of the bone fragments.
 Replacement of the fibrocartilagenous callus
by osseous callus which remodel along the line
of wt. bearing to complete repair.

73. In this region of a recent fracture, callus is seen forming at
the broken ends of bony trabeculae that extend to the
center from the left and top.

74. Healing……
 Immediately after the fracture, hematoma fills the
fracture site, seals off the fracture and provide
framework ingrowth of fibroblast and capillary &
give anchorage to the bone fragments.
 The platelets degranulate, inflammatory cells
migrate, PDGF, TGF-B, FGF, IL-s, are released, all
activate the osteoprogenitor cells in periosteum,
medullary cavity and surrounding soft tissue and
stimulate osteoclastic and osteoblastic activity.

75. Healing……
 At the end of the first week, the hematoma
organizes, a fusiform uncalcified tissue procallus
forms & provides the anchorage between the
two fractures ends but no structural rigidity
provided.
 Osteoprogenitor cells deposits trabecular of
woven bone in subperiosteal and in the
medullary cavity, the mesenchymal cells in soft
tissue differentiate into chondroblasts and
fibrocartilage and hyaline cartilage envelop the
fracture site.

76. Healing……
 The repair is maxim. in 2-3 weeks and this
fibrocartilagenous callous stabilize the fracture
site.
 The cartilage undergoes enchondral
ossification, the fibrocartilagenous callus
replaced by osseous callus which mineralizes
and remodel along the line of weight bearing
to complete repair.
 The callus excess is resorbed and the callus
reduced in size and shape until the outline of
the fracture is reestablished.

79. This is irregular new bone, or woven bone, which is forming
in the region of a fracture. Osteoblasts are seen lining the
irregular trabeculae, and there is an osteoclast near the
center.

80. Causes of defective repair
1. Malalignment.
2. Comminution and displacement.
3. Inadequate immobilization.
4. Infection
5. Systemic abnormalities (osteoporosis,
dietary insufficiency, atherosclerosis).
6. Malnutrition.
Pseudoarthrosis is false joint result from
interposition of soft tissue in the fracture

82. OSTEONECROSIS
(Avascular necrosis)
• Bone infarction is common
Sites - Medullary cavity of the metaphysis
- Diaphysis
- Subchondral region of the epiphysis

83. OSTEONECROSIS cont…..
Pathogenesis
All forms of bone necrosis result from ischemia.
Causes of ischemia:
1. Mechanical vascular interuption (fracture)
2. Corticosterides
follow high dose of corticosteroides therapy for
short term, or long term use of small doses or
intraarticular injections
3. Thrombosis and embolism (nitrogen bubbles/gas
emboli/Caisson disease)
4. Vessel injury (vasculitis, radiation)
5. Increased intraosseous pressure with vascular
compression
6. Venous hypertension
7. Uncertain causes

84. OSTEONECROSIS cont…..
Morphology:
Pathological features are the same with all causes
 Medullary infarct
- The necrosis is spotty involve cancellous bone and
marrow.
- Cortex not affected
 In subchondral infarcts
- A triangular wedge-shaped necrosis
- overlying articular cartilage not affected.

85. Note the wedge-shaped area of avascular necrosis
(osteonecrosis) at the upper right of this femoral head.
Avascular necrosis results from bone ischemia, which
can be due to many causes, including trauma and
corticosteroid administration, though idiopathic cases
are common. There is pain with activity, progressing to
pain at rest. Eventually, the necrotic bone collapses,
distorting the overlying articular cartilage and

86. OSTEONECROSIS

87. OSTEONECROSIS cont…..
Clinical course
• Subchondral infarcts cause chronic pain
first with activity, later at rest.
• Often collapse result in severe secondary
osteoarthritis.
• Medullary infarct clinically silent except
with large infarcts such occurring in
Gaucher disease or hemoglobinopathies.
• Remain stable over time rarely result in
malignancy.

88. PAGET’S DISEASE (OSTEITIS
DEFORMANS)
Paget’s disease described in 1876 by the British Sir James
Paget.
Incidence:
•It is common in whites in England, Australia, France,
Austria, USA and Germany.
•Rare in Scandinavia, China, Japan and Africa.
Age:
•Uncommon before the age of 40. It is an important predisposing
factor for osteosarcoma in elderly.
• It is an important predisposing factor for osteosarcoma
in elderly.
•Males > females .

89. PAGET’S DISEASE
Three phases
1. An initial phase of osteoclastic activity,
hypervascularity, and bone loss.
2. Phase of mixed osteoclastic and osteoblastic
proliferation.
3. A late “osteosclerotic” phase, formation of
dense mineralized bone.

90. Paget Disease
Pathogenesis
•Current evidence suggests a slow virus infection by
a paramyxovirus as the cause of Paget disease.
•Antigens and nucleic acids of paramyxoviruses
have been found in osteoclasts of affected
patients.

91. PAGET’S DISEASE cont…
MORPHOLOGY
Gross: Solitary lesion (monostotic in 15% ) , tibia,
ilium, femur, skull, vertebra and humerus.
Multifocal (polyostatic) in the pelvis,
spine
and skull in the remainder .
Sites: Any bone may be affected.

92. PAGET’S DISEASE cont…
Histology
1.Primary (osteolytic) phase
Rreplacement of marrow by loose vascular connective
tissue.
Trabeculae lined by multinculeated osteoclasts that cause
extensive resorption of bone.
2. Second (osteoblastic)phase
Osteoblast proliferation with mixed phase, bone
resorption
and new bone formation.
3. Third (osteosclerotic)phase
No osteoclastic activity, but bone deposition continues.

93. PAGET’S DISEASE cont….
• The new formed bone is woven bone but
become lamellar.
• The new bone is juxtaposed forming a random
mosaic pattern, and the appearance of a jigsaw
puzzle.
• The mosaic pattern of bone deposition is
pathognomonic of Paget’s disease. It is
produced by prominent cement lines that unite
haphazardly oriented lamellar bone.
• The bone is abnormally dense, but weaker and
subject to mechanical deformity and fracture.

94. PAGET’s DISEASE (of BONE)
Mosaic pattern of lamellar bone
CLINICAL: PAIN!!!
(MICROFRACTURES)

95. Paget Disease Clinical
• Pain is the most common problem and is localized
to the affected bone, the pain is caused by a
combination of micro-fractures and bone
overgrowth that compresses spinal and cranial
nerve roots.
• The diagnosis:
– It can frequently be made from the radiographic findings.
– Pagetic bone is typically enlarged with thick, coarsened
cortices and cancellous bone.
– Many patients exhibit an elevated serum level of alkaline
phosphatase and increased urinary excretion of
hydroxyproline.

96. Paget Disease Complications
 Bone overgrowth in the craniofacial skeleton
may produce leontiasis ossea and a cranium so
heavy that it becomes difficult for the patient to
hold the head erect.
 The weakened pagetic bone may lead to
invagination of the base of the skull and
compression of the posterior fossa structures.
 Weight bearing causes anterior bowing of the
femora and tibiae and distorts the femoral
heads, resulting in the development of severe
secondary osteoarthritis.
 Chalkstick-type fractures are the next most
common complication and usually occur in the
long bones of the lower extremities.
 Compression fractures of the spine result in
spinal cord injury and the development of
kyphoses.

97. Paget Disease Complications
 High-output heart failure or exacerbation of
underlying cardiac disease.
 The hypervascularity of pagetic bone warms the
overlying skin, and in severe polyostotic disease
the increased blood flow behaves as an
arteriovenous shunt leading to heart failure.
 A variety of tumor and tumor-like conditions
develop in pagetic bone.
 The benign lesions include giant cell tumor, giant
cell reparative granuloma, and extraosseous
masses of hematopoiesis.
 The sarcoma, occurs in 5% to 10% of patients with
severe polyostotic disease.
 The sarcomas are usually osteosarcoma,
malignant fibrous histiocytoma, or
chondrosarcoma

98. Paget Disease
bowing of legs

99. Assessment
The most common bone pathologies are:
A.Bone fractures
B.Genetic bone diseases
C.Inflammatory bone diseases
D.Malignant bone tumors

101. Lecture 4
Bone infections

102. OSTEOMYELITIS
Definition:
Inflammation of the bone and marrow cavity.
Causes:
The most common infectious agents :
pyogenic bacteria, mycobacterium tuberculosis.
Osteomyelitis acute or chronic is debilitating illness.
Osteomyelitis can be primary solitary focus or a
secondary complication of any systemic infection.

103. OSTEOMYELITIS cont….
Pyogenic Osteomyelitis
The routes of entry:
1. Hematogenous dissemination. The most
common route.
2. Direct extension from a focus of acute
infection in the adjacent joint or soft
tissue.
3. Traumatic implantation after compound
fractures.
4. Post operative complications
The primary source not always known.

104. OSTEOMYELITIS cont….
Causative agents:
• Staphylococcus aureus is the most common
• Haemophilus influenzae and group B
streptococci are causes of acute osteomyelitis
in neonates.
• Escherichia coli, pseudomonas and klebsiella
are involved in cases of genitourinary infection
and drug abusers.
• Salmonella is responsible for osteomyelitis in
patients with sickle cell disease.

105. OSTEOMYELITIS cont….
Morphology
Acute osteomyelitis of the bone is
characterized by:
1. Bacterial proliferation, acute intense
neutrophilic infiltrate at the site of bacterial
invasion.
2. Involved bone becomes necrotic in days
due to compression of vascular spaces.
3. Spread of infection from cortex to the
periosteum, creating subperiosteal abscess
(abscesses are common in children).

107. OSTEOMYELITIS cont….
Morphology cont..
4. From the subperiosteal area, infection spreads
to adjacent tissues create draining sinuses, or
may spread along the surface of the bone..
5. Detachment of the periosteum disrupt the
blood supply, ischemia and suppuration result
in segmental ischemic necrosis of the bone
called sequestrum.
6. In infants, infection spread to epiphysis and
joint capsule result in suppurative arthritis.
Extension less common in adults.

108. OSTEOMYELITIS cont….
Chronic Osteomyelitis
Is a sequela of acute infection.
1. Influx of chronic inflammatory cells in the
focus of osteomyelitis, osteoclast activation,
fibroblastic proliferation, and new bone
formation result.
2. The sequestrum (residual necrotic bone) will
be resorbed by osteoclastic activity.
3. Larger sequestra are surrounded by a rim of
reactive bone, termed the involucrum.

110. This is chronic osteomyelitis. Note the fibrosis of the marrow
space accompanied by chronic inflammatory cells. There
can be bone destruction with remodeling. Osteomyelitis is
very difficult to treat.

111. OSTEOMYELITIS cont….
Chronic Osteomyelitis cont:
4. Brodies abscess formed if sclerotic bone
surrounds small intraosseous residual
abscess. Viable organisms may persist in
the sequestered area for years.
5. Slcerosing osteomyelitis of Garre’, develop
in the jaw and is associated with extensive
new bone formation.
6. Chronic osteomyelitis may be complicated
by developing draining sinuses that open
on the skin.

112. OSTEOMYELITIS cont….
• Clinical Features
1. Systemic manifestations, fever, malaise, and
leukocytosis.
2. Local signs of bone inflammation easily missed in
infants and young children.
3. In adults, local pain, swelling and redness occur.
• Diagnosis
The X-ray appearance is lytic necrotic bone
surrounded by sclerosis seen a week after the onset
of systemic manifestation. Radionuclide scans
(gallium scans) helpful in locating the site of infection
early in course of osteomyelitis.

113. OSTEOMYELITIS cont….
Treatment
Prolonged antimicrobial therapy. Surgical
debridement.
Complications
• Pathologic fractures, acute bacterial arthritis.
• Bacteremia, septicemia, pyemia, endocarditis.
• Brodies abscess.
• Chronic
– Reactive systemic amyloidosis
– Squamous cell carcinomas of the sinus
tracts.

114. TUBERCULOUS OSTEOMYELITIS
• Incidence
Bone infection complicates 1% to 3% of cases of
pulmonary tuberculosis.
• Source of infection
1. Hematogenous from visceral focus (lung).
2. Direct spread from a contiguous focus of
infection (mediastinal nodes to the vertebrae).
3. Via lymphatic's

115. TUBERCULOUS OSTEOMY cont….
• Involved Bone
Spine of vertebrae (thoracic and lumbar) followed by
knee ,hips, ankle and small bones of hands and feet.
• Morphology
The lesions often solitary, may be multicentric
( immunodeficiency)
The lesions are typical granulomatous inflammatory
reaction with caseous necrosis and extensive bone
destruction.

116. TUBERCULOUS OSTEOMY cont.
• Tuberculosis of the vertebral bodies,(Pott’s disease).
Vertebral disc destruction, with deformity and collapse,
& with compression fractures and secondary
neurologic
deficits.
Extension of the infection to the adjacent soft tissue
causing abscesses (cold abscess) of the psoas muscle.
• Clinical presentation
Pain on motion, localized tenderness, low grade fever,
chills and weight loss, inguinal mass (the cold abscess).

118. Section of bone shows granuloma formation with epithelioid like cells , langhans-
type giant cells and rim of lymphocytes

119. TUBERCULOUS OSTEOMY cont…
Complications
1. Spread of infection
2. Tuberculous arthritis
3. Sinus tract formation with malignancy
4. Amyloidosis
5. Deformity of vertebrae, kyphosis, lordosis,
scoliosis

120. Assessment
 In pyogenic osteomyelitis, sequestrum is:
 a- The sinus draining the infected bone.
 b- The infected dead bone.
 c- The new reactive bone formed around the
dead bone.
 d- The soft tissue reaction around the infected
bone.