· process of increased bone remodelling
· initial increased resorption (osteoclastic activity)
· secondary increased reactive formation (osteoblastic activity)
· polyostotic or monostotic
· asymmetrical
· majority are asymptomatic
· 3-4% of those age > 40
· 10-15% of those age > 70
· more common in men
· racial and geographic variations
· common in British
· rare in Asians
· positive family history in 15%
· most common sites involved
· spine
· femora
· cranium
· pelvis
· not definitely known
· recent evidence supports virus
· likely paramyxoviridae family
· suggested by histology (giant multinucleated osteoclasts and intranuclear inclusion bodies)
· no definite virus isolated
· spongy
· generalised enlargement
· thickened cortices
· coarsened trabeculae
· frequently bowed due to poor structural integrity
· irregular segments of mature (lamellar) bone with
· increased cellularity (osteoclasts, osteoblasts and fibroblasts)
· increased vascularity
· multinucleated osteoclasts with nuclear inclusion bodies
· irregularly arranged cement lines
· resultant mosaic pattern is diagnostic
· two phases
Osteolytic (early)
· early in active phase, osteoclasts hyperactive
· leads to increased destruction with
· osteoporosis
· fibrovascular hyperplasia
Mixed
· resorption stimulates osteoblastic activity
· bone resorption and formation become balanced
· histologically abnormal bone produced
Osteosclerotic (late)
· osteoblastic activity exceeds osteoclastic activity
· sclerotic ivory-hard bone produced
· bone remodelling and turnover decrease toward normal
· what remains is bone that is
· enlarged
· sclerotic
· often deformed
· usually asymptomatic
· most common symptoms are pain and deformity
· other clinical presentations include
· pathological fractures
· neurocompression
· arthritis
· vascular shunting
· hypercalcaemia and hypercalcuria
· cardiovascular (esp. high-output cardiac failure)
· malignant degeneration
Bone pain
· due to metabolic activity of disease (? weakening of bone)
· deep and aching
· may be back pain, pelvic pain or limb pain
Neurological impingement
· back and typical radicular leg pain
Arthritis
· due to disturbance of subchondral bone and secondary derangement of joint mechanics
· hip usually shows loss of medial joint space (cf. superior with primary OA)
Impending fracture
· pain on weight bearing
· characterised by increased size and abnormal shape of bones
· skull enlargement, esp. frontal and occipital
· femora bow laterally and anteriorly
· tibia bow anteriorly and laterally
· incidence of 10-30%
· most frequently in
· femoral neck
· subtrochanteric femur
· tibias
· usually transverse or short oblique
· infiltration into inner ear
· neurosensory deafness from cochlear dysfunction
· conductive deafness from ossicle ankylosis
· mechanical compression on neural foramina of exiting cranial nerves
· softening and basilar invagination with vascular compression
· brain stem or cerebellar compression
· blockage of CSF flow with hydrocephalus
· high-output cardiac failure
· from increased bone blood flow
· pagetic steal syndrome
· from brain to external carotid system
· from spine to vertebral bodies
· rare (1%)
· but in those age > 70, 20-30% of bone sarcomas related to Pagets disease
· osteosarcoma or malignant fibrous histiocytoma
· uses
· confirm initial diagnosis
· monitor effects of treatment
· Ca++, PO4-- and PTH normal
· measure of osteoblastic activity
· correlates with disease extent
· may be normal with localised Paget’s disease
· 50% of ALP is of extraskeletal (hepatic) origin
· can distinguish hepatic cause by
· assessment of other LFTs
· assessment of urinary hydroxyproline
· marker of osteoclastic activity
· reflects collagen turnover
· 24 hour urine level measured
· rapidly reflects response to treatment
· disadvantage is lack of sensitivity
· new measure of bone resorption
· measures urinary excretion of hyrdroxy-pyridinium crosslinks of collagen
· derived from degradation of mature bone collagen
· may be more specific marker than hydroxyproline
· focal areas of bone resorption and formation that appear as radiolucencies and radiodensities
· overall bone size enlarged
· trabecular pattern coarsened and irregular
Active stage
Skull
· osteoporosis circumscripta
· sharply defined radiolucent area in cranium
Long bones
· flame sign
· flame-shaped osteolytic front extending from ends of long bones
Inactive stage
Skull
· cotton wool skull
· fluffy thickened areas of sclerotic bone
Spine
· cortical sclerosis with picture frame vertebra
· uniform sclerosis with ivory vertebra
Long bones
· sclerosis with cortical thickening
Complications
· bowing
· esp. femur and tibia
· pseudofractures
· “stress” fractures
· transverse incomplete fissures
· on convex aspect
· pathological fractures
· secondary arthritic changes
· esp. hip and knee
· high turnover leads to hot spot
· may be less hot with treatment or in inactive phase
· useful
· to confirm diagnosis
· as baseline
· useful to diagnose or exclude sarcomatous change
Pharmacotherapy
Definite
· pain (most common indication)
· spinal stenosis
Doubtful
· deafness
· deformity
· before orthopaedic operations
· high-output cardiac failure
Orthopaedic surgery
· severe arthritis of hip, knee or shoulder
· severe bowing of femur or tibia
· pathological fracture
· sarcomatous degeneration
Neurosurgery
· brainstem compression
· spinal cord compression
Calcitonin
· small polypeptide hormone
· secreted by parafollicular cells of thyroid
· potent inhibitor of osteoclastic activity
· human, salmon, eel, and porcine forms available
· must be given by injection
· intranasal spray recently available
· expensive drug
· minimal side-effects (nausea, flushing)
· dose as follows
· start with 50-100U daily
· reduce to three times a week after response
· usually see response within 2-6 weeks
· if no response within 3 months, discontinue
· relapse occurs in 30% of patients
· antibodies develop in 60% of patients
· only 10% have antibody-mediated resistance
· can be overcome by use of human form
Diphosphonates
· act as analogues of pyrophosphate
· interfere with growth and dissolution of hydroxyapatite crystals
· directly impair osteoclastic activity
· impair normal mineralisation of osteoid in high dose
· cause focal osteomalacia
· may lead to pathological fracture
· advantages over calcitonin
· oral administration
· less expensive
· relapse less common
· three forms
· etidronate (only one available in Aust)
· clodronate
· pamidronate
· etidronate used in two regimens
· 5 mg/kg/day for 6 months
· 20 mg/kg/day for 1 month (? less osteomalacia)
Mithramycin
· antibiotic with cytotoxic properties
· strong inhibitor of osteoclasts
· causes hypocalcaemia
· rapidly relieves pain from Pagets disease
· significant toxic side-effects
· only used for Paget's paraplegia
Serial treatment
· enhances effects and ameliorates side-effects
· calcitonin 50U S/C 3 times/wk for 6 months THEN
· etidronate 5 mg/kg/day for 6 months WITH
· one month overlap
Approach
Asymptomatic patients
· normal bone turnover
· no treatment
· increased bone turnover
· diphosphonates (APD) until normal
Symptomatic patients
· ensure pain attributable to Paget's disease
· normal bone turnover
· simple analgesia
· moderately increased bone turnover (ALP 2-3x normal)
· salmon calcitonin or diphosphonates
· very high bone turnover (ALP >3x normal)
· serial treatment with calcitonin and etidronate
Special problems
· use calcitonin in presence of impending or pathological fractures
· because of effect on mineralisation of diphosphonates
· try medical treatment first in spinal stenosis
· may decrease blood flow to vertebrae and prevent ‘steal’ syndrome
Fractures
Stress fractures
· try bracing and non-weight bearing
· if fails to heal in 3-6 months, prophylactic internal fixation
Completed fractures
· femoral neck fractures
· hemiarthroplasty preferable
· may have problem with protrusio
· consider THR if acetabulum involved
· intertrochanteric or subtrochanteric fractures
· orthodox techniques
· may have technical difficulties (enlarged sclerotic deformed bone)
· non-union common in subtrochanteric fractures
· femoral shaft fractures
· use nail
· tibial fractures
· usually treated closed
· fractures usually heal with abundant callus
· delayed union more common with sclerotic phase
· calcitonin useful to promote healing
Arthritis
· good success rates from arthroplasty
· only slight increased risk of hip arthroplasty loosening reported
· must plan preoperatively
· must differentiate joint pain from other causes
· metabolic pain
· nerve compression
Problems with THR
· increased bleeding
· sclerotic bone with difficult reaming
· bony deformities
· varus neck-shaft angle with tendancy for femoral component in varus
· protrusio acetabuli
· postoperative heterotopic bone formation
Osteotomy
· performed to
· improve deformity
· improve mechanics of weight-bearing joints
· good results from high tibial osteotomy if prerequisites present
· intertrochanteric hip osteotomy less reliable