Paget's Disease

 

Paget hipPagets Disease Tibia Femur

 

Definition

 

Skeletal disorder characterized by focal abnormalities of bone remodelling

 

Epidemiology

 

Incidence

 

Male > female

Caucasian

 

van Staa et al J Bone Miner Res 2002

- England database of 5 million patients

- 2500 patients with Paget's (0.3%)

- increasingly common with age

- increased incidence of back pain, OA, THA, TKA, fracture, hearing loss

- incidence sarcoma 0.3%

 

Declining prevalence

 

Poor et al J Bone Miner Res 2002

- reducing prevalence of Paget's disease in Britain over time

 

Etiology

 

Genetic factors

- family history / AD with incomplete penetrance

- genetic mutations lead to inability to bind ubiquitin, which activates osteoclasts

 

Environmental factors

- ? slow virus infection

- Paramyxovirus - measles / RSV

 

Pathophysiology

 

Primary abnormality

- intense focal resorption of normal bone by abnormal osteoclasts

- osteoclasts large, very active, numerous with excess nuclei

 

Response

- osteoblasts recruited and activity very rapid

- newly formed bone is not organized and remains irregular and woven in nature

- prone to deformity and fracture, especially in weight bearing extremities

 

3 phases

 

1.  Initial short lived resorption phase

- burst of multinucleate osteoclastic activity / marked elevation of serum alkaline phosphatase

 

2.  Mixed phase

- both osteoclastic and osteoblastic activity with structurally abnormal bone

 

3.  Final sclerotic phase

- bone formation exceeds bone resorption

 

Site

 

Polyostotic 65% / Monostotic 35%

 

Location - pelvis (70%), spine (50%), femur, tibia, and skull

 

Xray

 

Findings

- mixed lysis and sclerosis

- cortical thickening

- bone expansion and deformity

 

Pelvis

 

Paget hipPaget hip

Coxa vara / protrusio / OA

 

Femur

 

Paget femurPagets Disease Tibia Femur

 

Tibia

 

Pagets Tibia

Tibia deformity - sabre tibia

 

Lumbosacral spine

 

Bone scan

 

Shows increased uptake / will only detect active disease

 

Pagets Bone Scan

 

Biochemistry

 

Diagnosis - urinary hydroxyproline levels

Serum alkaline phosphatase - good indicator of activity

Calcium - may be elevated after bed rest

ESR - may be elevated in malignant transformation

 

Histology

 

Biopsy - rarely needed and predisposes to fracture

 

Histology

- poorly organised lamellar bone

- multinucleated osteoclasts

 

Pagets histology

https://www.pathologyoutlines.com/topic/bonepagets.html

 

Clinical Presentation

 

Usually incidental finding on x-ray or elevated alk phosphatase

 

Tan et al Calcif Tissue Int 2014

- systematic review

- bone pain most common presentation 52%

- bone deformity 23%

- fracture 9%

- deafness 9%

 

Issues

 

Bone deformity and fractures

Hip osteoarthritis with coxa vara and protrusio

Leonine skull - deafness / cranial nerve palsy

Spinal cord compression

Sarcomatous transformation 0.3%

 

Management

 

Bisphosphonates

 

Indication

 

Bone pain

 

Results

 

Corral-Gudino et al Cochrance Database 2017

- 20 studies and 3200 patients

- good evidence that bisphosphonates reduce bone pain

 

Langston et al J Bone Miner Res 2010

- RCT of bisphosphonate in 1324 patients with Paget's

- 3 year follow up

- no difference in hearing / fractures / need for orthopedic surgery

 

Surgical issues

 

Bleeding

- hypervascular bone

- pre-operative medication indicated if possible

 

Medical

 

Arif et al J Arthoplasty 2023

- systematic review of THA and TKA in Pagets

- 19 articles and 10,000 patients

- mortality 30% at 8 years

- increased medical complications

 

Hard bone

 

Parvizi et al PMR Summary article surgical management Pagets

 

Fracture

 

Paget fracturePaget fracture 2Paget fracture 3

 

Issues

 

Paget's fractures likely have normal healing capacity

 

Hard bone - difficult entry points

Bleeding

Deformity - may require osteotomy prior to IM nails

 

THA

 

Paget hip Paget THA

 

Technical issues

 

Bleeding

- preoperative calcitonin / bisphosphonates / EPO / Iron

- intra-operative blood salvage system

 

Acetabulum

- difficult reaming due to hard bone

- protrusio - consider medial bone graft / cages / lateral offset liners

- limited ability for cement interdigitation - uncemented cups may be preferrred

 

Femur

- coxa vara - risk varus femoral implants

- difficulty broaching femur - may need burrs

- femoral bowing - may need osteotomy

- poor cement interdigitation - uncemented stems may be preferred

- brittle bone - increased risk fracture

 

Heterotopic ossification

- high risk

 

Paget THA loosePaget THA loosePaget THA loose

Progression of disease and loosening of cemented acetabular component

 

Results

 

Martino et al J Orthop Traumatol 2021

- 66 registry patients with Paget's undergoing THA: 10 year survival 90%

- 29 institution THA

- 50% HO, 14% varus stems, high transfusion rates

 

Arif et al J Arthoplasty 2023

- systematic review of THA and TKA in Pagets

- 19 articles and 10,000 patients

- mortality 30% at 8 years

- revision rate 4% at 7 years

 

TKA

 

Pagets Disease Tibia FemurPagets Tibia

 

Technical  issues

 

Exposure difficult

- patella enlarged

- risk patella tendon avulsion

 

Bone very hard and deformed (tibial and femoral bowing)

- difficulties with IM and EM jigs

- navigation may be advantageous

 

Enlarged bones

- difficult releases

- may need different femoral and tibial components

 

Results

 

Arif et al J Arthoplasty 2023

- systematic review of THA and TKA in Pagets

- 19 articles and 10,000 patients

- mortality 30% at 8 years

- revision rate 2% at 7 years

 

Popat et al World J Orthop 2018

- 4 studies with 54 patients

- multiple intra-operative challenges: Malalignment, bone loss, soft tissue contractures

- 5% rate of patella tendon avulsion

 

Lumbar spine

 

Pathology

 

Lumbar (60%) / thoracic (45%) / cervical (14%)

 

Bony overgrowth

- foraminal compression - radiculopathy

- canal compression - spinal stenosis

 

Compression fractures

 

Xray

 

Sclerotic / Ivory vertebrae

- DDx: metastasis, lymphoma

 

Symptoms

 

Back pain

- Paget's

- degenerative changes

- fractures

- malignant transformation

 

Stenosis (33%)

 

Neural compression

 

Management

 

Calcitonin / bisphosphonates mainstay

 

Jorge-Mora Eur J Orthop Surg Traumatol 2016

- systematic review of 17%

- neurological decompression +/- fusion

- 44% major bleeding complication

 

Malignant Transformation

 

Pagets OS

 

Results

 

Ruggieri et al CORR 2010

- 26 patients with bone sarcoma arising from Paget's

- surgery +/- radiotherapy +/- chemotherapy

- 22/26 died at mean of 20 months