Paget's disease of the bone (reviewed)

Pre-operative treatment of PGD

Bisphosphonates to reduce disease activity in order to prevent severe bleeding.

Epidemiology of Paget's disease

1-2% of white adults >55 yo, male preponderance of 3:2.

Treatment of asymptomatic patients with active disease in an area with a high risk of complication.

1st line: Bisphosphonates with calcium and vitamin D supplementation to prevent hypocalcaemia (unless high risk for CVD). 2nd line: switch bisphosphonates for calcitonin.

Blade of grass lesions

Advancing v-shpae lytic lesions in the long bones.

Scintigram in PGD

Areas of dense uptake of isotope in pagetoid bone, non-specific, but helpful in identifying the extent of disease.

Most common presentation of Paget's disease

Asymptomatic (in around 70%) - incidental findings of elevated alk phos or on XR.

Genetics of Paget's disease

Autosomal dominant pattern of inheritance with variable penetrance. Sequestosome 1 gene, RANK and VCP genes implicated.

Common complications of Paget's disease

Bone pain and deformity Pathological fractures OA Deafness and tinnitus (nerve compression) Hypercalcaemia High output CCF (if >40% of skeleton involved) Osteosarcoma (suspect if sudden onset or worsening of bone pain)

Symptoms and signs of Paget's disease

Bone pain and deformity and enlargement Pathological fractures Raised skin temperature over areas of active disease Cranial nerve impingement (hearing loss, facial pain, deterioration of visual acuity) Loosening or disturbance in chewing Angioid streaks in the retina.

Paget's disease of the bone

Chronic bone disorder characterised by increased bone resorption, bone formation and remodelling. a.k.a. osteitis deformans.

Nerve impingement in Paget's disease

Chronic non-specific inflammation and occasional narrowing of the various foremens.

Total serum alkaline phosphatase measurement in PGD

Elevated in 85-100% of cases. ALP +++

Indication for CT or MRI scan in PGD

Evaluate neurological involvement.

Bone deformity in Paget's

Head: Frontal bossing (enlargement of the forehead) and prognathism (progressive enlargement of the mandible). Spine: kyphosis. Leg: Sabre tibia (bowing of the tibia).

Ischaemic myelitis

High metabolic and vascular demand of pagetoid bone steals blood supply from the nearby spinal cord and nerve roots, creating a vascular deficit.

Rare complications of Paget's disease

Hypercalcaemia, hydrocephalus, high-output cardiac failure, paraplegia, osteosarcoma and kidney stones.

Indication for bone biopsy in PGD

If malignant change is suspected. Findings in PGD: presence of osteoclast with multiple nuclei, wide cannaliculi with disorganised matrix and a mosaic pattern of poorly organised lamellar bone.

Treatment of symptomatic patients

If pain relief fails: 1st line: Bisphosphonates (adjunct: calcium and vit D) + supportive therapies (pain relief: paracetamol, ibuprofen, aspirin, celecoxib). 2nd line: calcitonin + supplements + supportive therapies.

Urinary and serum pyridinoline and hydroxyproline.

Initially elevated and may be normalised by treatment, markers of bone resorption.

urinary and serum N-telopeptide and C-telopeptide.

Initially elevated and may be normalised by treatment, markers of bone resorption.

Polyostotic Paget's disease

Involves more than 1 bone (usually the femur, pelvis, skull or tibia) and occurs in 75% of patients.

Monostotic Paget's disease

Involves only 1 bone (femur is the most common site), occurs in 25% of cases.

3 phases of Paget's disease

Osteoclastic/lytic phase- marked elevation of serum alkaline phosphatase. Mixed phase of osteoclastic and osteoblastic activity. Final chronic sclerotic phase, during which bone formation outweighs bone resorption.

Bone pain in Paget's

Long bone or back pain, usually due to microfractures.

ESR in Paget's disease

Men >20mm/hour, women >24mm/hout, highly sensitive, non-specific. Increased ESR may indicate malignant transformation.

Pathophysiology of Paget's disease

Metabolic hyperactivity- intense focal resorption by abnormal osteoclasts creating voids and cavities, abnormal newly formed bone laid down.

Bone specific alkaline phosphatase measurement in PGD

More sensitive than total serum alk phos.

Plain XR findings in early stage PGD

Mostly lytic changes seen as radiolucency, occasional incomplete fractures.

cotton wool skull

Multifocal sclerotic patches in the skull.

Serum 25-hydroxyvitamin D

Normal in Paget's, differentiate with fibrous dysplasia or osteomalacia.

LFTs in PGD

Normal, useful to monitor for liver disease causing an increased alkaline phosphatase.

Presentation of spinal stenosis

Paraesthesias and muscle weakness.

Most common sites affected by Paget's disease

Pelvis, femur and lower lumbar vertebrae.

Osteosarcoma prognosis

Poor prognosis: most die within three years.

Osteosarcoma

Rare, complicating 0.10-1.15% of PGD. Malignant tumour of the bone.

Prognosis of PGD

Remission may be possible with successful treatment.

Plain XR findings in later stage PGD

Sclerotic picture predominates, cotton wool pattern in the skull (multifocal sclerotic patches), pseudo fractures.

Monitoring of treatment efficacy in PGD

Serial monitoring of alkaline phosphatase. Urinary and serum pyridinoline and hydroxyproline, and urinary and serum N-telopeptide and C-telopeptide are markers of bone resorption. Markers measured after 6 months of treatment. Markers subsequently measured every 6-12 months or until symptoms reappear or increase.

Less common complications of Paget's disease

Spinal stenosis, nerve compression syndrome and cauda equina syndrome.

Presentation of osteosarcoma in PGD.

Sudden onset or worsening of chronic pain and elevated ESR.

Isotope used in bone scintigraphy

Tc-bisphosphonate

Aetiology of Paget's disease

Unknown, genetic, immunologic, infection and environmental suggested.

CRP in PGD

Usually elevated.

Serum calcium in PGD.

Usually normal, hypercalcaemia in some circumstances.

Treatment of asymptomatic patients (incidental diagnosis)

Vigilance Pharmacological therapy not usually required.

Hearing loss in Paget's

narrowing of foramen for 8th cranial nerve and effects on ear ossicles (stapes fixation) and cochlear dysfunction.

Serum PTH in PGD.

usually normal.

Serum phosphate in PGD.

usually normal.