Paget's Disease of Bone

Definition

Condition characterised by high rates of bone resorption and disorganised immature new bone formation ® abnormal remodelling of bone

First described by Sir James Paget in 1876 and evidence of the disease found in Neanderthal man


Incidence

Affects more than 3% of population over 40 years of age around 2% of the population at age 40 to around 10% in the elderly (more than 80 years)

Relatively common in Anglo-Saxons, Britain, Germany and Australia

Britain has the highest recorded prevalence

In Australia the prevalence among British born immigrants is intermediate between the British rate and the native born Australians

Rare in Scandinavia, Russia, Italy, Asia, Africa and the Middle East

Affects American whites and blacks equally ® suggest environmental factor contributing to aetiology

Male : Female 7:6

Probably equal overall incidence but in younger individuals males slightly more frequent

Only occasionally presents in people under 50 years

There is evidence of a decline in incidence of the disease in Britain and USA


Aetiology

The primary abnormality is thought to lie in the osteoclasts but the precise cause remains unknown

Viral aetiology

suggested by the isolation of viral intra-nuclear inclusion bodies in osteoclasts on EM which resemble those of measles (Rebel 1976, Mills 1976)

Antigen to measles virus, simian virus 5 and human parainfluenza virus type 3 detected in abnormal osteoclasts (Basle 1985)

Measles virus not detected (Gordon 1991)

Canine distemper virus (CDV) in 41% of Pagetic osteoclasts, osteocytes and osteoblasts (Gordon 1991)

Slow virus type aetiology consistent with familial incidence

Ralston, 1994 investigated Pagets and normal bone with reverse-transcriptase and polymerase chain reaction

no difference in IL-1, IL-6, TNF-?, TNF-?, b-FGF, TGF-?, IGF-1

possibility that Pagets bone turnover is due to local elaboration of other osteotropic factors

Birch (Ralston) 1994 unable with PCR to detect measles and CDV aetiology for Pagets disease

Relationship to pets has been postulated but not substantiated

Genetic, as family history found in 15 - 20% of cases, and the site and extent of disease similar in family members (dominant inheritance with low penetrance (Sofaer 1983)

Extraordinary geographic variations in prevalence (see data on incidence)

Probably, Pagets disease is caused by infection with a common and widespread virus superimposed on genetic variation for susceptibility and perhaps severity of disease (Sofaer, 1983)

Interaction between hereditary and environmental factors

Geographical variations in the prevalence of Paget's disease remain unexplained and the viral hypothesis remains unproven

Also postulated

a disorder of hormonal secretion

vascular aetiology

autoimmune disease

monoclonal IgM


Clinically

Variable picture with the majority being discovered incidentally following X-Ray or elevated alkaline phosphatase

Only a minority of patients become symptomatic (5%)

Monostotic in 17% and polyostotic in 83% (pelvis 70%, Lumbar spine 50%, femur 50%, skull 45%, tibia 30%, humerus 30%, clavicle ® visible deformity in 13%, hand and foot 3 - 5%)

The disease may for many years be localised to part or the whole of one bone

Affected bones may remain asymptomatic or ® pain (dull constant ache) and become bent

Pain is worse at night, but rarely severe unless sarcoma or fracture supervene

Lesions detected on bone scan are usually painful whereas many lesions seen on X-Ray are not

Bone looks bent, feels warm (may be 5o warmer than unaffected side)and thick (osteitis deformans)

If generalised may ® headache, deafness (with impairment of hearing in 30 - 50% of cases), deformities, stiffness, limb pain and sometimes fracture and heart failure, occasionally pressure on the optic nerve may ® blindness

Facial and trigeminal nerves may also be affected

Spinal stenosis may occur ® root or cord problems infrequently or a vascular steal syndrome may ® spinal claudication

Features suggestive of pain of Pagetic origin in the back are non-specific low back pain without radiculopathy, normal or minimal findings on examination, vertebral sclerosis in radiographs, isolated vertebral involvement in bone scan and enlarged vertebra and neural arch, normal facet joints and no bony impingement

Canal stenosis occurs gradually as the expanding vertebral body reduces the canal diameter, may be kyphosis, and back ache and root pain is common

Cardiac failure associated with arterial calcification and calcification of heart valves and myocardium as well as being a high output state

About 20% of Pagets patients have fractures which may be complete or incomplete and as many as 40% ® delayed or non-union

Tinnitus and vertigo are common complaints

Coxa vara is also a feature with considerable antero-lateral bowing of the legs

When involves a joint may ® painful erosive arthritis due to altered stresses secondary to deformity and abnormal subchondral bone ® collapse or loss of resilience

X-Rays

Early ® osteoporosis circumscripta

Disease involvement usually seen at one end of the bone (generally proximal)

The bone as a whole is thick and bent

Density in the vascular stage is decreased and it is increased in the sclerotic stage

Trabeculae are coarse and widely separated

In vascular stage areas of porosis shape