Lecture 3 - finished

Question 1

Pagets Disease definition

Answer 1

A common, benign metabolic bone disease characterised by the thickening and disturbance of architecture of the affected bone

Question 2

What is Pagets disease characterised by?

Answer 2

High rates of bone resorption

The formation of disorganised, immature bone

Question 3

What is the pagets disease process due to?

Answer 3

Abnormal remodelling of bone

Question 4

Pagets epidemiology

Answer 4

Males more than females (7:6)
Usually begins 40+ (2% of 40+ year olds)
Rare before 50yoa (1% of population over 50 have it)
By 9th decade, males = 10%, females = 15%

Question 5

Prevalence of pagets in australia?

Answer 5

4% of the population over 55 have it. Therefore it is common.

Question 6

Pagets aetiology:

Answer 6

Idiopathic
The theory is that genetically predisposed people will develop Pagets if they encounter certain viruses.
Slow viral infection of osteoclasts
The paramyxovirus group is thought to be involved
- measles virus
- respiratory syncytial virus
- canine distemper virus

Question 7

Classifications of Pagets

Answer 7

Monostotic = 15%

Polystotic = 85%

Question 8

Bone affected in Monostotic Pagets Disease:

Answer 8

Monostotic Pagets:
Tibia
Femur
Skull
Vertebrae
Humerus

Question 9

Bone affected in Polystotic Pagets Disease:

Answer 9

Polystotic Pagets: 
Spine
Pelvis
Femur
Skull
Sacrum
Tibia
Humerus

Question 10

Pathology of Pagets:

Answer 10

Abnormal remodelling of bone
High rates of bone resorption
Disorganised immature bone formation
Increased vascularity of affected bones

Question 11

Stages of Pagets Disease

Answer 11

1 - Osteolytic
2 - Mixed Osteolytic/osteoblastic
3 - Osteosclerotic

Question 12

Describe the osteolytic phase of Pagets Disease

Answer 12

Normal bone is resorbed by abnormal osteoclasts.
These osteoclasts are bigger, more numerous, have more nuclei than normal, and contain micro cylindrical inclusions.
Bone turn over rate can be up to 20 times normal.

Question 13

Describe the mixed osteolytic/osteoblastic phase of pagets

Answer 13

Resorption is closely followed by new bone formation but they are uncoupled/ don’t occur in a balanced fashion.
New matrix is haphazardly laid down as woven bone.
Bone volume remains mostly normal.

As a result:

• mineralisation of matrix lags
• osteoid seams persist, demarcating the margins of newly laid bone
• tile like/mosaic pattern of bone formation is pathognomonic
• new bone is highly vascularised
• adjacent bone marrow spaces fill with loose, highly vascularised connective tissue

UNCOUPLED IS THE KEY WORD IN THIS STAGE

Question 14

Describe the osteosclerotic phase of pagets

Answer 14

After many years in stage 2, the condition burns out/becomes quiescent.
Key features of this stage:
 - formation of new bone is
    = disordered
    = poorly mineralised
    = of poor structural stability
    = vulnerable to fracture and deformation
 - osteosclerosis

Question 15

What are the macroscopic features seen in the osteosclerotic phase of Pagets disease?

Answer 15

Anterior bowing of long bones
Sagging of femoral neck
Enlarged, deformed skull
Coarsened facial bones (leontiasis ossea)
Vertebral:
- cortical thickening
- trabeculae coarsening
- poorly formed bone
- tendency to collapse leading to kyphosis

Question 16

What are the structural properties of pagets affected bones?

Answer 16

Bone is:

• soft
• porous
• eventually enlarges

The bone has:

• poor structural stability
• an increased risk of deformity
• an increased risk of fracture

Question 17

What are the clinical manifestation of Pagets disease

Answer 17

Asymptomatic (usually monostotic form)

Pain (most common ssx, mostly occurs in the polystotic form, due to #, nerve compression and secondary OA)

Bone deformity

• skull enlargment
• femur and tibial bowing
• facial bones (leontiasis ossea)
• vertebral # and collapse

Bone enlargement

Warmth over affected bones (increased vascularity)

Sponginess of bones on palpation

Neurological manifestations

Question 18

What are some neurological ssx that may occur with pagets and why?

Answer 18

Expanding bone may put pressure on nerves, the brain or spinal cord resulting in:

• headache
• hearing loss/tinnitus
• visual disturbances
• various neuropathies

Question 19

What are the radiological findings of pagets?

Answer 19

Osteolytic phase = flame lesions (patchy radiolucent lesions)
Sclerotic stage = irregular sclerosis
Later stages = bone enlargement

Question 20

What are the complications of Pagets disease:

Answer 20

Musculoskeletal:

• pain
• bone deformity
• pathological #
• secondary OA

Neurological:

• nerve compression (ie carpal tunnel, sensorineural deficits)
• radiculopathy
• spinal stenosis and myelopathy

Cardiovascular:
- increased CO because of the increased vascularisation of the lesions puts more strain on the heart. Can lead to altherosclerosis, CHF, aortic valve calcification etc.

Neoplastic:
- Osteosarcoma

Question 21

Fibrous dysplasia definition

Answer 21

A benign focal slowly expanding lesion in which bone in slowly replaced by a mass of fibroblasts, collagen and irregular bone trabeculae of woven bone.

Fibrous dysplasia is a focus of disordered maturation of bone with arrest at the immature stage of woven bone

Question 22

What are the 3 types of fibrous dysplasia?

Answer 22

Monostotic
Polystotic
Albrights Disease

Question 23

Describe monostotic fibrous dysplasia

Epidemiology
Sites of involvement
Aetiology
Pathology
Clinical manifestations

Answer 23

Epidemiology:

• 70% of cases
• Both sexes equally
• Usually begins at childhood with progression often stopping its progress at puberty.

Sites of involvement:

• ribs (most common)
• femur
• tibia
• mandible
• maxilla

Aetiology:
increased osteoclast numbers
increased fibroblast numbers

Pathology:
- Affected bone is replaced by:
= proliferating fibroblasts
= scattered trabeculae of irregular woven bone
- the usual rim of osteoblasts around the bone trabeculae is absent

Clinical manifestations:
- usually asymptomatic
- the lesion may cause
   = tumourous distortion of the bone
   = disfigurement of face/skull
   = pain

Question 24

Describe polystotic fibrous dysplasia

Epidemiology
Sites of involvement
Clinical manifestations

Answer 24

Epidemiology:

• 25% of cases
• both sexes equally
• appears at an earlier age than monostotic

Sites of involvement:

• uni or bilateral
• femur (most common)
• skull
• tibia
• humerus
• ribs

Clinical manifestations:

• craniofacial bones affected in 50% with moderate disease and 100% in patients with extensive disease
• shoulder and pelvic girdles severely affected
• multiple skeletal deformities seen
• pain due to fractures (characteristic)

Question 25

What is Albrights disease:

Answer 25

• A form of polystotic fibrous dysplasia with
○ Multiple unilateral bone lesions
○ Unilateral pigmented skin lesions
○ Autonomous endocrine hyperfunction

• Some endocrinopathies seen are:
○ Acromegaly
○ Hyperthyroidism
○ Cushings syndrome

Skin lesions usually on same side of the body as the bone lesions and are large pigmented areas of dark coloured “café-au-lait”, irregular serpiginous borders

Question 26

Describe the typical bone lesion in fibrous dysplasia

Answer 26

Affected bone is replaced by proliferating fibroblasts, amongst which are scattered trabeculae of irregular woven bone. The usual rim of osteoblasts around the bone trabeculae is absent.

Question 27

Describe a lytic lesion:

Answer 27

A well circumscribed lesion of reduced bone density positioned in the medullary regions of the bone. Might see slight expansion of the bone and cortex but wont see any erosion of the cortex by the lesion.
There will be no evidence of trabecular bone but will have speckled ‘ground glass’ type of appearance.

Question 28

What are the radiological manifestations of fibrous dysplasia?

Answer 28

Usually presents as a lytic bone lesion (bone cyst)

Affected bone has a ‘ground glass’ radiolucent appearance. The lesion is well demarcated from normal bone.

Question 29

What are the complications of fibrous dysplasia?

Answer 29

Pathological #

Osteosarcoma (rare)