Paget's disease

Question 1

What is Paget’s disease (osteitis deformans)?

Answer 1

• Usually begins in the fifth decade of life
• Paget’s disease is an inflammatory disease & it’s affected by an interplay of genetics and environmental factors, which is triggered when there’s a genetic mutation
• Males are more affected
• It has three stages:

1) Initial osteolytic stage, characterized by excessive bone resorption

2) Mixed osteolytic-osteoblastic stage, ending with a predominance of osteoblastic activity

3) The final stage is the osteosclerotic stage, which is inactive and characterized by the formation of osteoid

Question 1

Describe the stages of Paget’s disease more precisely

Answer 1

1) Hypervascular/osteolytic phase:

• Initial phase of disorder that involves bone resorption by osteoclasts

2) Intermediate phase:

• Osteolytic + osteoblastic activity

3) Exhaustive (burnout) stage:

• Abnormal matrix persists but the cellular activity is nearly absent
• Later on, the bone will be in an acellular phase where the only thing visible is the osteoid (osteoid is poorly mineralized), Although the bone is thick and dense but fragile = Paget’s disease

Question 2

Describe the pathogenesis of Paget’s disease of bone

Answer 2

1) Genetics: increases osteoclast (most commonly SQSTM1 mutation)

2) Viruses: measles, etc

3) Local factors: Repetitive mechanical trauma, and increased blood flow

4) Environmental factors: Low dietary calcium, Vitamin D deficiency, toxins and pesticides

5) Thyroid deficiency

Question 3

What is the importance of the thyroid function test in Paget’s disease?

Answer 3

THE THYROID GLAND CONTROLS THE BODY’S METABOLISM, AND PAGET’S CAN BE CAUSED BY THYROID DEFICIENCY

Question 4

Describe the morphology of cells in Paget’s disease (osteitis deformans)

Answer 4

• The histologic landmark is the mosaic pattern of lamellar bone
• As the new bone formed in active disease is disordered and poorly mineralized, it is soft and porous and lacks structural stability, it is also liable to fracture or deformity under stress

Question 5

What are the different types of Paget’s disease?

Answer 5

1) Monostotic type: One bone is affected, 15% of cases affect bones like the tibia, ilium, femur, skull, vertebrae, or humers

2) Polystotic: 85% of the cases, affecting more than one bone at the same time, like the pelvis, spine, and skull

Question 6

What are the clinical features of Paget’s disease?

Answer 6

1) In the early stage of the disease, there are deformities of bones e.g. kyphosis (bending forwards and outwards of the tibia and femur)

2) Later on the bones become hardened and thickened

3) Deformities of the bones of the skull may produce headaches, visual disturbances, and deafness

4) Back pain is common, and it may be associated with disabling vertebral fractures and spinal nerve root compression

5) The long bones of the legs may undergo chalk-stick-type fractures

6) Osteosarcoma may occur in less than 1% of patients.

• If the femur or tibia is affected then the patient will show symptoms in the gait
• If the skull thickens then the patient will show symptoms such as headaches, hearing or visual disturbances due to the entrapment of nerves
• If the patient is affected by the vertebra there could be entrapment of the nerves or lower back pain

Question 7

What are the different diagnostic techniques used to diagnose Paget’s disease?

Answer 7

1) Blood:

• ALP - Classicaly elevated
• Gamma-FT: rules out the liver cause of increased ALP

2) Bone scan:

• Shows increased uptake in affected bones

3) Urinalysis:

• It will often contain collagen due to the high bone resorption

4) X-rays:

• Lytic and sclerotic lesions (lots of dark blobs in the bone)
• Widening of the bone cortex
• Bone deformities

Question 8

What is the treatment of Paget’s disease?

Answer 8

• It is based on the symptom severity

1) Bisphosphonates: like pamidronate (reduces osteoclast activity “2 months can induce remission”)

2) Analgesics

3) Treat the complications (like maybe a joint replacement)