paget's disease of bone

Question 1

definition

Answer 1

Chronic localised bone remodelling disorder characterised by increased bone resorption, bone formation, and remodelling, which may lead to major long-bone and skull deformities. This unbalanced process may lead to osseous deformities, altered joint biomechanics, nerve compressions, and pathological fractures.

Question 2

pathogenesis

Answer 2

The main feature of Paget’s disease is localised areas of metabolic hyperactivity of bone. The primary abnormality is believed to be in the osteoclasts, which are abnormally large with excess nuclei. Pagetic osteoclasts are responsible for increased bone resorption, causing large resorption pits and cavities.[28] Bone formation is linked to resorption and, in order to compensate for the increased resorption, osteoblast activity is dramatically increased in pagetic lesions. The osteoblast activity is so rapid that newly-formed bone is not organised and remains irregular and woven in nature. The newly formed woven bone is less resistant and more elastic than typical lamellar bone and, hence, prone to deformity and microfractures, especially in the weight-bearing extremities. There is a high degree of vascularity in the pagetoid bone, which, in conjunction with the microfractures, is thought to be the cause of pain in patients with underlying Paget’s disease of the bone.[29]

Paget’s disease evolves through three distinct phases:

An initial, short-lived burst of multinucleate osteoclastic activity causing bone resorption
A mixed phase of both osteoclastic and osteoblastic activity, with increased levels of bone turnover leading to deposition of structurally abnormal bone
A final chronic sclerotic phase, during which bone formation outweighs bone resorption.
The continued process of excessive, abnormal bone-forming activity and creation of microfractures results in deformities, with resultant change in the biomechanical milieu of the adjacent joints. The latter, combined with old age, predisposes these patients to arthritis.[30] In the skull and spine, the resultant changes lead to a chronic non-specific inflammation and, occasionally, narrowing of the various foramens, resulting in cranial and spinal nerve impingement. Ischaemic myelitis is rarely seen; this is hypothesised to be due to the high metabolic and vascular demands of pagetoid bone, which steals the blood supply away from the nearby spinal cord and nerve roots.

Question 3

risk factors

Answer 3

• familial history of paget’s
• > 50 y/o
• male 45-74 y/o
• infection (Paramyxoviruses such as the measles virus, respiratory syncitial virus, and canine distemper virus have been implicated in the aetiology of Paget’s disease)
• environmental factors (high levels of arsenic may be a factor in the aetiology of Paget’s disease)

Question 4

signs and symptoms

Answer 4

!! paget’s is asymptomatic in most people !!

• femoral / pelvis / skull involvement
• long-bone or back pain (due to micro factures/spinal stenosis due to narrowing of spinal canal/due to the blood-steal mechanism where the new bone vasculature steals blood from the other bones)
• bony deformities (e.g. frontal bossing, prognathism aka lower jaw sticking out, bone bowing)
• increased local temperature (due to high metabolic activity)
• hearing lost / visual impairment (cranial nerve impingement)
• facial pain
• loss of teeth / difficulty chewing

Question 5

investigations

Answer 5

1st investigations

• plain x ray
• bone scan
• total serum ALP
• bone specific ALP
• serum calcium (could have hypercalcaemia, but usually normal)
• serum P1NP (procollagen 1 N-terminal peptide) (marker of bone formation)
• serum CTX (C-terminal propeptide of type 1 collagen) (marker of bone resorption
• LFTs (make sure raised ALP not from liver disease)
• serum 25-hydroxyvitamin D (normal in paget’s, not normal in osteomalacia or fibrous dysplasia. used to differentiate.)

others:
- CT/MRI
- bone biopsy