Lecture notes on bone pathology

1. BONE PATHOLOGY
BY
F. CHAPIMA
B.Sc. (UNZA), MSc. Clinical Pathology (UNZA)

2. Introduction
 Musculoskeletal system is comprised of the
bones, joints and the muscles.
 Bones have three roles which are;
 Mechanical support
 Mineral storage and
 Haematopoiesis.

3. Introduction ……………….
Mechanical functions of bone include;
 Protection for the brain, spinal cord and chest
organs;
 Rigid internal support for limbs and
 Deployment as lever arms in the skeletal muscle.

4. Introduction ……………….
 Joints (articulations) serve as a union between
bones and are necessary for the mechanical role
of bone.

5. Lecture outline
Bones
1.Congenital diseases of bone
2. Acquired diseases of bone development
3. Fractures
4. Osteonecrosis
5. Osteomyelitis
6. Metabolic bone disease
7. Bone tumors

6. Congenital Diseases Of Bone
 Congenital diseases of bone range from localized
malformations to hereditary disorders associated
with abnormalities affecting the entire skeletal
system.
 Can result in the absence of bones, extra bones,
or inappropriately fused bones;
 these are typically due to mutations in genes
affecting localized migration and condensation of
primitive mesenchymal cells

7. 1. Achondroplasia
 Achondroplasia refers to a syndrome of short-
limbed dwarfism and macrocephaly, which
represents a failure of normal epiphyseal cartilage
formation.
 It is the most common genetic form of dwarfism
(1:15,000 live births) and is inherited as an
autosomal dominant trait.

8. 1. Achondroplasia……………….
 These people have normal mentation and life
spans.
Pathogenesis
 Achondroplasia is caused by mutations in the
fibroblast growth factor receptor 3 (FGFR3) on
chromosome 16.

9. 1. Achondroplasia……………….
 The mutation inhibits proliferation and
differentiation of chondrocyte which impedes
growth plate development.
Clinical features
 Clients have short stature
 The average height of an adult male is 131 cm
adult females is 124 cm.

10. 1. Achondroplasia……………….
 Have an average-size trunk,
 Short arms and legs
 Short arms have limited range
of motion at the elbows
 A big head (macrocephaly)
with a prominent forehead.

11. 2. Scoliosis and Kyphosis
 Scoliosis is an abnormal lateral curvature of the
spine, usually affecting adolescent girls.
 Kyphosis refers to an abnormal anteroposterior
curvature.
 When both conditions are present, the term
kyphoscoliosis is used.

12. 2. Scoliosis and Kyphosis …………….
Pathogenesis
 A vertebral body grows in length (height) from the
endplates of the vertebrae, which correspond to
the growth plates of long tubular bones.
 As in tubular bones, vertebral bodies increase in
width by appositional bone growth from the
periosteum.

13. 2. Scoliosis and Kyphosis …………….
 In scoliosis, for unknown reasons, one portion of
the endplate grows faster than the other,
producing lateral curvature of the spine.
Clinical features
 If kyphoscoliosis is severe, the patient may
develop, corpulmonale and joint problems
particularly involving the hip.

14. 2. Scoliosis and Kyphosis …………….
Treatment
 The treatment of scoliosis is appropriate stress on
the vertebral body through the use of braces or
internal fixation to straighten the spine.

15. 3. Osteogenesis Imperfecta (OI)
 OI refers to a group of genetic (mainly autosomal
dominant) disorders of connective tissue due to
mutations in the gene for type I collagen.
 It affects the skeleton, joints, ears, ligaments,
teeth, sclerae and skin
 It is characterized by hard and easily broken
bones often from little or no apparent cause.

16. 3. Osteogenesis Imperfecta …………
Pathogenesis
 The pathogenesis of OI involves mutations of
COL1A1 and COL1A2 genes which encode the α1
and α2 chains of type I procollagen, the major
structural protein of bone.
 These genes are located in chromosomes 17 and 7
respectively.

17. 3. Osteogenesis Imperfecta …………
 Mutations causes substitution of other amino
acids for the glycine type I collagen at every third
residue.
Clinical features
 This depends on the type of OI

18. 3. Osteogenesis Imperfecta …………
Type I
 Mildest form
 Multiple fractures when child begins walking and
sitting
 Blue sclera (thin sclera with underlying choroids)
 Hearing abnormalities (fusion of ossicles)
beginning in early 20s or 30s.
 Extremely thin and curved bones and bluish
yellow teeth

19. 3. Osteogenesis Imperfecta …………
Type II
 Most severe form.
 Numerous fractures and
severe bone deformity.
 Small stature with
underdeveloped lungs.

20. 3. Osteogenesis Imperfecta …………
Type III
 Short stature.
 Barrel-shaped rib cage.
 Bone deformity, often
severe.
 Brittle teeth possible.
 Hearing loss possible.

21. 3. Osteogenesis Imperfecta …………
Type IV
 Similar to type I
 White sclera
 Bone cortex may mature during adolescence or
afterwards

22. Lecture outline
Bones
1. Congenital diseases of bone
2.Acquired diseases of bone development
a) Fractures
b) Osteonecrosis
c) Osteomyelitis
3. Metabolic bone disease
4. Bone tumors

23. 1. Fractures
 The fracture is the most common bone lesion and
is defined as a discontinuity of the bone .
Pathogenesis
 The lesion typically results from blunt trauma to
the muscle and soft tissues, usually of the lower
limb; however, some cases occur spontaneously.

24. 1. Fractures ………….
 Fractures can be classified as traumatic,
pathological or stress fractures
Common causes
 Trauma. A fall, a motor vehicle accident, or
trauma during a football game can all result in
fractures.

25. 1. Fractures ………….
 Pathological fractures - Osteoporosis. This
disorder weakens bones and makes them more
likely to break (pathological fractures).
 Overuse. A stress fracture refers to an
accumulation of stress-induced micro fractures,
which eventually result in a true fracture through
the bone cortex.
 They can result from repeated mechanical injury.
 Stress fractures are more common in athletes.

26. 1. Fractures ………….
Common types of fractures
 Stable fracture. The broken
ends of the bone line up and
are barely out of place.
 Open or compound fracture.
The skin is pierced by the bone
that breaks the skin at the
time of the fracture.
 The bone may or may not be
visible in the wound.

27. 1. Fractures ………….
 Transverse fracture. This type
of fracture has a horizontal
fracture line.
 Oblique fracture. This type of
fracture has an angled pattern.
 Comminuted fracture. In this
type of fracture, the bone
shatters into three or more
pieces.

28. 1. Fractures ………….
Signs and Symptoms
 Pain on the affected area
 Un able to move the injured limb.
Other common symptoms include:
 Swelling and tenderness around the injury area
 Bruising
 Deformity — a limb may look "out of place" or a
part of the bone may puncture through the skin

29. 2. Osteonecrosis
 Osteonecrosis (ON) refers to death of bone in the
absence of infection.
Causes/ Risk factors
 Long-term steroid treatment
 Alcohol abuse
 Joint injuries
 Having diseases such as arthritis and cancer

30. 2. Osteonecrosis …………..
Pathogenesis
 Cancellous bone and cortex undergo different
mechanisms of repair.
 Necrotic cancellous bone heals by creeping
substitution, in which the necrotic marrow is
replaced by invading neovascular tissue, thus
providing the pluripotential cells necessary for
bone repair.

31. 2. Osteonecrosis …………..
 In non-traumatic ON there is embolization by
blood clots or lipid droplets.
 This leads to the death of osteocytes and bone
marrow followed by the repair processes to
remove necrotic bone and marrow and replace
them with viable tissue.
 If the infarct is small, this process may succeed.

32. 2. Osteonecrosis …………..
 However, in some patients, the
process is not successful and
the infarct gradually collapses.
 The overlying articular surface
becomes flattened and
irregular, causing increased
pain and eventually leading to
osteoarthritis.

33. 2. Osteonecrosis …………..
Symptoms and Signs
 Patients may remain asymptomatic for weeks to
months after the vascular insult.
 Pain then develops gradually with progressive
collapse of the joint
 Pain increases and is worsened by motion and
weight bearing and is relieved by rest.

34. 3. Osteomyelitis
 Osteomyelitis is an inflammation of the bone
and the bone marrow.
Causes
 Commonly caused by Staphylococcus aureus
(Pyogenic Osteomyelitis) and Mycobacterium
tuberculosis (Tuberculous Osteomyelitis)

35. 3. Osteomyelitis ……………..
Micro – organisms can enter a bone in 3 ways;
 Via the bloodstream
 From a nearby infection
 Direct contamination.

36. 3. Osteomyelitis ……………..
Pathogenesis
 Osteomyelitis primarily affects the metaphyseal
area because of vascular supply in this region
 If the organism is virulent and continues to
proliferate, it creates increased pressure on the
adjacent thin-walled vessels in the marrow cavity.

37. 3. Osteomyelitis ……………..
 Such pressure further compromises the vascular
supply in this region and produces bone necrosis.
 The necrotic areas coalesce into an avascular
zone thereby allowing further bacterial
proliferation.

38. 3. Osteomyelitis ……………..
Signs and symptoms
 Fever or chills
 Irritability or lethargy in young children
 Localized bone pain
 Swelling, warmth and redness over the area of the
infection

39. 3. Osteomyelitis ……………..
 Sometimes osteomyelitis
causes no signs and
symptoms or has signs and
symptoms that are difficult
to distinguish from other
problems.

40. 3. Osteomyelitis ……………..
Complications
 Osteonecrosis - Bone death
 Septic arthritis
 Impaired growth
 Skin cancer. If osteomyelitis has resulted in an
open sore that is draining pus, the surrounding
skin is at higher risk of developing squamous cell
cancer.

41. 4. Tuberculosis of Bone
 Tuberculosis of bone originates from the lung or
lymph nodes, and reaches the bone by
haematogenous spread.
 Often affects the spine, termed as Tuberculous
spondylitis or Pott disease is a complication of
childhood tuberculosis and affects the bodies of
the vertebrae, with sparing of the lamina
 The thoracic vertebrae are most commonly
affected.

42. 4. Tuberculosis of Bone ……………
Pathology
 The pathology in Tuberculous spondylitis is
similar to tuberculosis at other sites.
 The granulomas first produce caseous necrosis of
the bone marrow, which leads to slow resorption
of bony trabeculae and, occasionally, to cystic
spaces in the bone.

43. 4. Tuberculosis of Bone ……………
 Because there is little or no reactive bone
formation, affected vertebrae usually collapse,
leading to kyphosis and scoliosis.
 The intervertebral disk is crushed and destroyed
by the compression fracture, rather than by
invasion of organisms.

44. Lecture outline
Bones
1. Congenital diseases of bone
2. Acquired diseases of bone development
a) Fractures
b) Osteonecrosis
c) Osteomyelitis
3.Metabolic bone disease
4. Bone tumors

45. 1. Osteoporosis
 Osteoporosis AKA “porous
bone” is a disease characterized
by increased sponginess of the
bone resulting from reduced
bone mass.
Classifications
 Osteoporosis can be primary or
secondary due to some other
factor.

46. 1. Osteoporosis ……………
Primary disorder can further be classified as;
 Type 1 or postmenopausal osteoporosis is
associated with decreased levels of oestrogen and
has a greater effect on trabecular than cortical
bone.
 Type 2 or senile osteoporosis is a consequence
of aging and is often augmented by inadequate
calcium and vitamin D intake.

47. 1. Osteoporosis ……………
Peak bone mass
 Osteoblasts and osteoclasts (cells that resorb
bone) are regulated by parathyroid hormone
(PTH), calcitonin, estrogen, vitamin D, various
cytokines, and other local factors such as
prostaglandins.
 Normally, bone formation and resorption is
closely balanced.

48. 1. Osteoporosis ……………
 Under normal conditions, bone mass peaks
between the ages of 25 and 35 years and declines
thereafter.
 Blacks reach higher bone mass than whites
 Men have higher bone mass than women.
 After achieving peak for about 10 years, bone loss
occurs at a rate of about 0.3 to 0.5%/yr.

49. 1. Osteoporosis ……………
 In menopause, bone loss is accelerated to about 3
to 5%/year for about 5 to 7 years and then the
rate of loss slows.

50. 1. Osteoporosis ……………
Pathogenesis
 Osteoporosis occurs when bone loss exceeds bone
formation, resulting in a low bone mass.
 Thus, this disease should be viewed in the
context of failure of the remodelling cycle to
replace all the resorbed bone.

51. 1. Osteoporosis ……………

52. 1. Osteoporosis ……………
Risk Factors
 Race (Caucasians > African Americans)
 Sex (F > M)
 Physical inactivity
 Slender body build
 Early menopause
 Increasing age
 Calcium nutritional state - insufficient dietary
intake.

53. 1. Osteoporosis ……………
Signs and Symptoms
 Patients with osteoporosis are
asymptomatic unless a fracture
has occurred.
Gross morphology
 The trabecular plates become
perforated, thinned, and lose
their interconnections, leading to
progressive micro fractures.

54. 2. Osteomalacia and Rickets
 Osteomalacia refers to a softening of bones,
often caused by vitamin D deficiency in
adults.
 Rickets is the softening and weakening of
bones in children, usually because of an extreme
and prolonged vitamin D deficiency.

55. 2. Osteomalacia and Rickets …………..
Pathogenesis
 Vitamin D promotes the absorption of calcium
and phosphorus from the gastrointestinal tract.
 Deficiency of vitamin D makes it difficult to
maintain proper calcium and phosphorus levels
in bones, which can cause soft bones .
 Soft bones are more likely to bow and fracture
than are harder and healthy bones.

56. 2. Osteomalacia and Rickets …………..
Sign and symptoms
 The most common
signs and symptoms
are bowled legs.

57. 3. Paget’s disease of the bone
 Paget disease ( osteitis deformans) is a localized
disorder of bone remodeling, resulting in
excessive bone resorption followed by
disorganized bone replacement, producing
thickened but weak bone that is susceptible to
deformity and fracture.

58. 3. Paget’s disease of the bone………..
 It is related to a virus infection with
paramyxovirus, and also possibly to have a
genetic predisposition.
 Paget disease begins after age 40 years and is
common in those of European ancestry.

59. 3. Paget’s disease of the bone………..
Pathogenesis
 Paget disease develops in 3 stages:
 The osteolytic stage ( osteoclastic activity
predominates)
 The mixed osteolytic-osteoblastic stage
 The osteosclerotic stage (osteoblastic activity
predominates in this "burnout stage")

60. 3. Paget’s disease of the bone………..
Pathology
 Involved bones are thick but weak and fracture
easily.
 Skull involvement leads to increased head size
and foraminal narrowing that can impinge on
cranial nerves, often leading to deafness.
 Involvement of facial bones may produce a lion-
like face.

61. 3. Paget’s disease of the bone………..
Complications
 Arteriovenous shunts within marrow, which may
result in high-output cardiac failure
 Increased incidence of osteosarcoma and other
sarcomas.

62. Lecture outline
Bones
1. Congenital diseases of bone
2. Acquired diseases of bone development
a) Fractures
b) Osteonecrosis
c) Osteomyelitis
3. Metabolic bone disease
4.Bone tumors

63. Benign tumors of bone
Osteoma
 is a benign neoplasm that frequently involves the
skull and facial bones.
 Osteoma can be associated with Gardner
syndrome.

64. Benign tumors of bone………………
Osteoid Osteoma
 Osteoid Osteoma is a benign, painful growth of
the diaphysis of a long bone, often the tibia or
femur.
 It affects males more than females, with peak age
5 to 25 years.
 The pain tends to be worse at night and relieved
by aspirin.

65. Benign tumors of bone………………
 X-rays studies show central radiolucency
surrounded by a sclerotic rim.
 Microscopically, these tumors show a small (<2
cm) lesion of the cortex characterized by a central
nidus of osteoid surrounded by dense sclerotic
rim of reactive cortical bone.

66. Benign tumors of bone………………
Osteoblastoma
 Osteoblastoma is a tumor that is similar to an
osteoid osteoma but is larger (>2 cm) and often
involves vertebrae.

67. Benign tumors of bone………………
Osteochondroma
 Osteochondroma (exostosis) is a benign bony
metaphyseal growth capped with cartilage that
originates from epiphyseal growth plate.
 It typically presents in adolescent males who have
firm, solitary growths at the ends of long bones.

68. Benign tumors of bone………………
 Osteochondromas may be
 Asymptomatic
 Cause pain
 Produce deformity or
 Undergo malignant
transformation (rare)

69. Malignant tumors of bone
Osteosarcoma
 Osteosarcoma ( osteogenic sarcoma) is the most
common primary malignant tumor of bone, and
the tumor occurs more frequently in males than
females.
 Most cases occur in teenagers (ages 10-25 years),
and patients with familial retinoblastoma have a
high risk.

70. Malignant tumors of bone………………
 Secondary osteosarcomas occur in elderly
persons.
 These highly aggressive tumors are associated
with Paget disease, irradiation, and chronic
osteomyelitis.

71. Malignant tumors of bone………………
Clinically
 localized pain and swelling.
 The classic x-ray findings are
Codman triangle (periosteal
elevation), "sunburst“ pattern,
and bone destruction.
 The treatment is with surgery
and chemotherapy.
 The prognosis is poor

72. Malignant tumors of bone………………
Pathology
 Grossly, osteosarcoma often involves the
metaphyses of long bones, usually around the
knee (distal femur and proximal tibia).
 The tumor produces a large, firm, white-tan mass
with necrosis and hemorrhage.

73. Malignant tumors of bone………………
Chondrosarcoma
 Chondrosarcoma is a malignant tumor of
chondroblasts that may arise de nova or
secondary to a pre-existing enchondroma or Paget
disease.
 Males are affected more frequently than females,
with peak age 30—60 years.

74. Malignant tumors of bone………………
 Chondrosarcoma presents with enlarging mass
with pain and swelling, and it typically involves
the pelvic bones, spine, and shoulder girdle.

75. Malignant tumors of bone………………
Ewing sarcoma
 Ewing sarcoma is a malignant neoplasm of
undifferentiated cells arising within the marrow
cavity.
 Males are affected slightly more often than
females.
 Most cases occur in teenagers (age range 5-20
years).

76. Malignant tumors of bone………………
Clinically
 Patients present with pain, swelling, and
tenderness.
 X-ray studies show concentric "onion-skin"
layering of new periosteal bone.
 The tumor is treated with chemotherapy, surgery,
and/or radiation, and has a 5-year survival rate
of 75%.

77. Malignant tumors of bone………………
Metastatic Tumors
 Metastatic Tumors are the Most Common
Malignant Tumors in Bone
 Most metastatic lesions to bone are carcinomas,
particularly of the breast, prostate, lung, thyroid
and kidney.
 It is estimated that haematogenous skeletal
metastases are found in at least 85% of cancer
cases that have run their full clinical course.

78. Malignant tumors of bone………………
 The vertebral column is, by far, the most common
site in adults, and the appendicular skeleton is
the typical location in children.

79. References
 Robbins, S.L, Kumar, V and Abbas, K (2010). Pathologic Basis of Disease
(8th Edition). W.B Saunders Company, Philadelphia.
 Robbins SL and Kumar V (2007). Basic Pathology (8th Edition).WB
Saunders Co. London.
 Harsh Mohan, (2010). Textbook of Pathology (6th Edition). Jaypee
brothers medical publishers (p) ltd, India
 Riede and Werner, Color Atlas of Pathology © 2004 Thieme
 Rubin E, Rubin R, Strayer D.S. (2012) Rubin`s Pathology:
Clinicopathologic Foundations of Medicine (6th Edition), Lippincott
Williams & Wilkins, a Wolters Kluwer business. Philadelphia, PA.
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