Paget’s disease

Published on 02/04/2015 by admin

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Last modified 22/04/2025

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229 Paget’s disease

Instruction

Examine this patient’s face.

Examine this patient’s legs.

Salient features

History

• Ask the patient whether there is an increase in hat size

• Bone pain

• Joint pain (from osteoarthritis secondary to bone disease)

• Painless bowing of the bone can be the first symptom

• Hearing loss

• Fractures with minimal trauma

• Nerve entrapment syndromes including paraparesis and radioculopathy when the spine is affected.

Examination

• Face:

• Comment on the hearing aid, if any; test hearing and determine whether the deafness is a conduction defect (from involvement of the ossicle) or neural (from compression of the eighth nerve)
• Typical appearance of the skull and increased skull diameter (>55 cm is abnormal)
• Tell the examiner that you would like to examine the fundus for optic atrophy or angioid streaks.

• Neck:

• Look for platybasia
• Raised JVP (cardiac failure in Paget’s disease is caused by hyperdynamic circulation).

• Spine:

• Deformity of the spine: kyphosis
• Auscultate over the vertebral bodies for bruits
• In up to one-third of patients the third and fourth lumbar vertebrae are involved, and in 20% the lower thoracic vertebrae are involved.

• Legs:

• Comment on the anterior bowing of the tibia (Fig. 229.1D) and the lateral bowing of the femur
• Feel the bone for warmth
• Tell the examiner that you would like to examine the joints for osteoarthritis (limitation of hip movement, in particular abduction, and fixed flexion deformity of the knees).

• Proceed by tell the examiner that you would like to:

• Do a urine analysis (high incidence of renal stones)
• Measure the patient’s height (for serial follow-up)
• Compare the patient’s appearance with a previous photograph
• Ask the patient whether there is an increase in hat size.
image

Fig. 229.1 (A) Radiograph of tibia, showing bone deformity, expansion and alternating areas of osteosclerosis and osteolysis with a pseudofracture on the convex aspect of the tibia. (B) Radionuclide scan showing increased tracer uptake in affected femur. (C) Pathological fracture through affected femur. (D) Severe tibia deformity.

(With permission from Ralston et al. 2008.)

Remember: Paget’s disease is a remodelling disease of isolated areas of the skeleton.

Diagnosis

This patient has Paget’s disease (lesion) with hyperdynamic cardiac failure and sensorineural deafness (functional status).

Questions

What are complications of Paget’s disease?

• Diminished mobility

• Fractures

• Basilar invagination can lead to a ‘Tam O’Shanter’ deformity

• Cord compression from basilar invagination

• Narrowing of basal foramina, producing cranial nerve lesions, especially deafness, and occasionally compression of the medulla oblongata or upper spinal cord

• Root lesions as a result of vertebral damage

• Hypercalcaemia

• High-output cardiac failure

• Sarcomatous changes are seen in <2% of patients.

Advanced-level questions

Mention the neurological complications of Paget’s disease

• Headache

• Fits

• Platybasia

• Hydrocephalus

• Cerebellar signs

• Cranial nerve palsies

• Cord compression.

What are the mechanisms of hearing loss in such patients?

• It is usually caused by the disease process involving the ossicles

• Less commonly it is caused by the progressive closure of the skull foramina compressing the eighth cranial nerve.

What is the basic defect in bone metabolism?

Increased osteoclastic activity resulting in bone resorption and increased osteoblastic activity.

What are the radiological manifestations of this disease?

• Skull: ‘honeycomb’ appearance with underlying osteoporosis circumscripta, ‘cottonwool’ appearance

• Pelvis: thickening of the iliopectineal line ‘brim-sign’, enlargement of ischial and pubic bones

• Long bones: increased trabeculation and localized bone enlargement

• Vertebra: sclerotic margins giving a ‘picture frame’ appearance.

Remember: A bone scan is more sensitive than a radiograph in determining the extent of disease.

What is the prevalence of Paget’s disease?

The exact prevalence is not known but several reports indicate a 3% prevalence in those >40 years of age and this increases with age to reach a maximum of 10% by the ninth decade. Males predominate by a ratio of about 2 : 1.

What factors have been implicated in the aetiology of Paget’s disease?

• Slow viral infection: measles syncytial virus, paramyxovirus (canine distemper)

• Genetic factors: mutations have been identified in at least four genes. The most important of these is SQSTM1, encoding sequestosome 1, a scaffold protein in the nuclear factor NF-κB signalling pathway. Patients with SQSTM1 mutations have severe Paget’s disease of bone and a high degree of penetrance with increasing age

• Other potential triggers include deficiency of dietary calcium and repetitive mechanical loading of the skeleton.

Note: Juvenile Paget’s disease, a genetic bone disease characterized by accelerated bone turnover, results from inactivating mutations in the gene encoding osteoprotegerin (an important modulator of osteoclastogenesis). Osteoprotegerin is a member of the superfamily of tumour necrosis factor receptors (TNFRSF11B) and is a receptor activator of NF-κB RANK ligand (RANKL).

What are the biochemical features of this disease?

• Serum calcium concentration is normal (except in prolonged immobilization or malignancy).

• Increased bone serum alkaline phosphatase, indicating increased osteoblastic activity.

• Increased urinary hydroxyproline secretion, indicating increased bone resorption.

Which drugs are commonly used in the treatment of this disease?

• Bisphosphonates, which inhibit osteoclast-mediated bone resorption (aledronate)

• Calcitonins, which acts by reducing osteoclastic activity.

To which patients would you offer therapy?

Treatment is offered to patients with any of the following symptoms:

• Agonizing bone pain, headache with skull involvement, fissure fracture

• Prior to surgery such as potential hip replacement

• Severe deformity

• Hypercalcaemia

• Cardiac failure.

Sir James Paget (1814–1899), Surgeon at St Bartholomew’s Hospital, London. He also described Paget’s disease of the nipple (carcinoma involving the areola and the nipple), Paget’s disease of the skin (skin cancer involving the apocrine glands) and Paget–Schroetter syndrome (venous thrombosis of the axillary veins, of unknown cause). (Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans 1877;60:37).

Stuart Ralston, FRCP is Professor and holds the ARC Chair of Rheumatology at the University of Edinburgh has written extensively on Paget’s disease.

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