Picture Quiz

Case history

A 91 year old woman was admitted with subacute bowel obstruction, which resolved with conservative management. Discharge was delayed, however, because of poor mobility secondary to gross bone deformation (fig 1 and 2). The patient's biochemistry showed a markedly raised concentration of alkaline phosphatase, with normal serum concentrations of calcium and phosphate.

Questions

1. What is the diagnosis?
2. What abnormality does the x ray film show?
3. What is the treatment?

Discussion

Paget's disease of bone is a common disorder. It affects 3% of people aged under 40 years and 10% of those aged over 90 years. Its aetiology is still unknown although recent research suggests that a paramyxovirus is responsible, along with genetic and environmental factors. The disease is commonly seen in northern Europe and the north west of England, whereas it is comparatively rare in Africa, Asia, and northern America.

The disease is characterised by excessive bone turnover, which results in abnormal bone architecture. The pathological process is initiated by osteoclast mediated bone resorption to which there is a compensatory increase in osteoblast mediated bone formation. This new bone is highly vascular and disorganised, and it gradually becomes enlarged and structurally weakened. Paget's disease can affect one or more sites, most commonly the lumbosacral spine, skull, pelvis, femur, and tibia, although all parts of the skeleton may become affected.

Presentation

Paget's disease is most commonly an incidental finding and becomes symptomatic in just 2% of those who have it. Common presentations are:

1. Bone pain - Due to associated osteoarthritis, impingement of bone upon nerve roots, or pathological fractures.
2. Bone deformity - Skull enlargement can compress cranial nerves, causing deafness and visual impairment. Spinal cord compression can cause a spastic paraparesis. Kyphosis and bowing of the extremities are common.
Rare presentations are:
3. High output cardiac failure.
4. Malignant transformation into osteogenic sarcoma.
5. Hyperuricaemia and clinical gout.

Figure 1

Diagnosis

This is made on the basis of biochemical and radiographic findings. The hallmark of Paget's disease is a raised concentration of alkaline phosphatase, in the presence of normal serum concentrations of calcium and phosphate, reflecting the greatly increased bone turnover. However, mild hypercalcaemia may follow prolonged immobilisation. Levels of urinary hydroxyproline, a normal breakdown product of collagen, are also markedly increased, and this and the concentration of alkaline phosphatase parallel the course of the disease and provide useful markers of therapeutic progress.

Radiographically, Paget's disease starts at one site in a bone and gradually extends, the advancing front becoming lytic. This is classically seen in the skull and is known as osteoporosis circumscripta. As bone formation becomes more prominent, patchy areas of sclerosis and enlargement occur, deformity being a later sign.

Radionucleotide bone scans can help in locating areas of active disease, which show as "hot spots." These can be difficult to distinguish from metastatic carcinoma.

Figure 2

Treatment

When asymptomatic, Paget's disease may require no treatment at all. Mild pain is usually controlled with non-steroidal anti-inflammatory drugs, but in more severe cases the drugs of choice are the bisphosphonates. These are extensively taken up in bone matrix hydroxyapatite crystals and inhibit osteoclast activity. Given orally or intravenously once daily over 6 months, they have been shown effective in reducing progression of the disease in about 75% of cases and can offer a prolonged remission; treatment may therefore be necessary for only 6 months of a year. Bisphosphonates have largely superseded the use of synthetic analogues of calcitonin, which have the disadvantages of cost, invasive delivery, and, occasionally, antibody formation, which can render them ineffective. Very severe cases can be treated with a combination of the above. Mithramycin, a cytotoxic antibiotic, can also be used, but its use is limited by nephrotoxic, hepatotoxic, and haemotoxic side effects. Very rarely surgery may be necessary to treat complications such as cord compression.

Opinion is currently divided among clinicians over whether to treat asymptomatic disease. The progressive nature of and possible implications for the quality of a patient's life have led many to recommend treatment, especially with the advent of cheap, effective, and well tolerated treatment. Currently, however, there are no supportive clinical data, and the management of many patients is based on clinical observation.

James Ryan, senior house officer in medicine

Mohammed Ehtisham, consultant physician, City Hospital NHS Trust, Birmingham B18 7QH


studentBMJ 1999;07:394-436 November ISSN 0966-6494

Answers
1. Paget's disease of bone.
2. Pagetoid "sabre" tibia.
3. None, NSAIDs, bisphosphonates.