Paget disease Flashcards
What is the pathophysiology of Paget’s disease ?
In Paget’s disease there is bone resorption due to increased osteoclastic activity which is compensated initially by osteoblast activity. The disease process begins when osteoclast release RANKL which binds on to the RANK on osteoclast. The RANKL activated osteoclasts start secreting collagenese and Hcl which digest collagen and dissolve the minerals that make up the bone matrix. Once there is sufficient bone resorption, the osteoblasts release osteoprotegeran (OPG) which arrest osteoclast activity by inhibiting RANKL. The osteoblasts then secrete osteoid seam which which generates collagen matrix for new bone formation.
What is the etiology of Paget’s disease ?
The exact cause is not know. However it can be triggered by viral infections such as measles and genetic mutations such as SQSTM1 mutation.
The most commonly affected bones in Paget’s disease ?
The skull, lumbar vertebre, pelvis and femur.
What are the phases of Paget’s disease ?
Phase 01: The lytic phase
Phase 02: The mixed phase
Phase 03: sclerotic phase
What happens in the lytic phase of Paget’s disease ?
Osteoclasts with upto 100 nuclei aggressively demeneralize the bones 20 times more than normal.
What happens in the mixed phase of Paget’s disease ?
In this phase the pathological process in lytic phase co-occurs with that of the blastic phase in which there is rapid disorganised proliferation of new bone tissue by an unusually large number of osteoblasts causing collagen fiber deposition in a haphazard way.
What happens in the sclerotic phase ?
In this phase the formation of structurally disorganised and weaker bones exceeds bone resorption.
What is the final or the dormant stage of paget’s disease ?
It is a state of burn out marked by the cessation of osteoblastic activity.
What is the symptomatology of Paget’s disease ?
Early stage - asymptomatic
Over time misshapen bones can impinge nerves and cause neuralgia. The skull involvement can cause Leontiasis, and cranial nerve entrapment syndromes. In addition, Paget’s disease induced genetic mutations can cause Paget’s osteosarcoma, kyphosis, arthritis, proximal and distal myopathies, and genu varum.
What are the diagnostic work up in Paget’s disease ?
- significant elevation of alkaline phosphate.
- X-ray may show lytic lesions during the lytic phase or cortical thickening of the affected bones in advanced phases.
- A bone biopsy should be done to exclude malignancies that mimic Paget’s disease.
What are the Treatments for Paget’s disease ?
- pain relief medications.
- Anti-bone resorption agents such as bisphosphonate, denosumab, Romosozumab etc.
- surgical and non surgical therapy for entrapment syndromes.
