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Metabolic bone disease

In this second and final article on bone conditions, Professor Juliet Compston answers questions from GP Dr Madhu Valuri

In this second and final article on bone conditions, Professor Juliet Compston answers questions from GP Dr Madhu Valuri

1. I have a patient with parathyroid adenoma who is not suitable for surgery but is troubled by symptoms of hyperparathyroidism such as tiredness, aches and pains, and lack of appetite. What are the main principles of managing this type of patient in primary care?

These symptoms are likely to be due to hypercalcaemia and would therefore respond to parathyroidectomy.

In some centres this is now done on a day case basis as a minimally invasive procedure and can therefore be performed even in frail patients. However, if surgery is not a feasible option, hypercalcaemia can be controlled using bisphosphonates in the doses used to prevent osteoporotic fractures. This treatment will also reduce the risk of osteoporosis, which is increased in patients with primary hyperparathyroidism.

In early postmenopausal women, oestrogen therapy may also be used to control hypercalcaemia. Finally, calcimimetic agents such as cinacalcet reduce hypercalcaemia associated with hyperparathyroidism. Approximately 25% of patients with primary hyperparathyroidism show progression of disease over a 10-year period. Most patients are under the age of 50. Serum calcium and creatinine should therefore be checked once or twice a year. Bone densitometry should be assessed at baseline and appropriate intervals thereafter, depending on the initial values.

2. Which patients taking bisphosphonates are most at risk of osteonecrosis of the jaw, and are bisphosphonates still the treatment of first choice in these patients? How long should bisphosphonates be continued?

In the context of bisphosphonate therapy, osteonecrosis of the jaw has most commonly been reported in patients receiving large doses of intravenous bisphosphonates for the treatment of cancer (in most cases breast cancer and multiple myeloma).

It is extremely uncommon with the doses used for treatment of osteoporosis; current estimates in this population are in the region of 0.7/100,000 person exposure years. An important risk factor for osteonecrosis of the jaw is dental disease, particularly in infection or conditions requiring major dental procedures. Current advice is that in such individuals, dental advice and treatment should be sought before starting bisphosphonate therapy.

Alternatively, another treatment option such as strontium ranelate could be offered. Glucocorticoid therapy and chemotherapy may also increase the risk of osteonecrosis of the jaw. If significant dental problems arise in a patient already established on bisphosphonates, there is no evidence that stopping treatment affects the risk of developing osteonecrosis of the jaw.

3. How can we detect patients with hyperparathyroidism secondary to CKD? What percentage of these patients are likely to develop renal osteodystrophy? At what point should we refer to secondary care?

Secondary hyperparathyroidism develops in most patients with CKD. Symptomatic manifestations are uncommon but if untreated, secondary hyperparathyroidism may result in increased rates of bone loss and fragility fractures.

The key diagnostic test in secondary hyperparathyroidism is serum parathyroid hormone. Serum phosphate is often increased but serum calcium levels are generally normal. In some cases bone biopsy is required to make a firm diagnosis.Management of secondary hyperparathyroidism associated with CKD is complex and best carried out in secondary care. Since it develops early in the course of CKD, early referral to secondary care is recommended. Regular monitoring of serum PTH levels and vitamin D status should be performed. Treatment includes the use of phosphate binders, vitamin D metabolites and analogues, correction of acidosis and calcimimetic agents. In some cases tertiary hyperparathyroidism develops and para-thyroidectomy is required.

4. Which patients with osteomalacia should we refer for a specialist opinion? How long should we prescribe vitamin D and calcium supplementation for when treating patients with osteomalacia and how should the patients be monitored?

Osteomalacia occurs when prolonged and severe vitamin D deficiency results in defective mineralisation of bone. Its clinical manifestations are often non-specific and diagnosis is usually based on abnormal serum biochemistry, particularly a raised serum alkaline phosphatase, low serum 25-hydroxy- vitamin D and increased parathyroid hormone level.

Pathognomic radiological changes are usually only seen in very severe cases. Where the diagnosis is uncertain, bone biopsy may be indicated. Most cases of osteomalacia are due to privational vitamin D deficiency (reduced exposure to sunlight or low dietary intake) but other rare causes include tumour-induced osteomalacia and inherited forms of the disease. Osteomalacia is rare nowadays and, if it is suspected, merits referral for a specialist opinion since diagnosis and definition of its cause are often not straightforward. Complete reversal of the defective mineralisation in bone takes several years and, depending on the cause, vitamin D therapy may need to be continued indefinitely. Treatment can be monitored using bone function tests and serum 25-hydroxyvitamin D and parathyroid hormone levels.

5. Which people are at risk of vitamin D deficiency and what preventive measures can be advised?

Those most at risk are the elderly and those who are housebound or living in institutions. The latter group includes not only elderly individuals but also young people, for example those with learning difficulties. Other groups at risk of vitamin D deficiency include Asians (particularly women), patients with malabsorption and those with some forms of renal disease.

Prolonged use of anticonvulsants in treatment for epilepsy may increase the risk of vitamin D deficiency, although this was mainly seen with phenytoin and phenobarbitone and does not appear to be associated with the more modern anti-epileptic treatments. Since the availability of vitamin D in food is relatively restricted, preventive measures generally consist of vitamin D supplementation. In most situations a daily dose of 800IU is sufficient to correct vitamin D deficiency but higher doses may be required in patients with malabsorption. Where practicable, exposure to sunlight may also be advised, although prolonged exposure should not be recommended because of the increased risk of skin cancer.

6. One of our elderly patients had a hip X-ray following a fall to exclude a fracture which incidentally showed features suggestive of Paget's disease. What does this mean for the patient? Would a rheumatology referral be appropriate?

Paget's disease is not an uncommon incidental finding on X-rays performed for other indications. In the absence of pain or significant skeletal deformity, treatment is not generally indicated.

However, involvement of bone in the area of the fracture by Paget's disease would constitute a strong indication for treatment and referral to a rheumatologist. An increase in serum alkaline phosphatase level indicates active disease and also merits referral to a rheumatologist.

7. How common is osteogenesis imperfecta and how is it diagnosed?

The true prevalence of osteogenesis imperfecta is unknown, since milder forms are difficult to detect. However, the disease is likely to contribute to only a small proportion of fractures attributed to osteoporosis.

The clinical spectrum of osteogenesis imperfecta is extremely broad, ranging from lethal neonatal forms to mild disease that is indistinguishable from age-related osteoporosis. In young children with the milder forms of osteogenesis imperfecta, non-accidental injury is a key differential diagnosis. A family history of osteogenesis imperfecta is a useful clue to the diagnosis but is by no means invariable. Clinical features may include blue sclerae, yellowish or opalescent teeth, and joint hyperextensibility but these are not present in all patients with the disease. In most cases the diagnosis can be confirmed by DNA sequencing of blood samples, although a negative result does not completely exclude the presence of osteogenesis imperfecta.

Professor Juliet Compston is professor of bone medicine at the University of Cambridge

Competing interests None declared

Take-home points

• Day case parathyroidectomy can be performed on even quite frail patients with hypercalcaemia. Otherwise bisphosphonates can be used.

• Osteonecrosis of the jaw is rare at normal bisphosphonate doses but dental advice should be sought if any dental disease occurs.

• The key diagnostic test in secondary hyperparathyroidism is serum parathyroid hormone as serum calcium levels are generally normal.

• In osteomalacia, complete reversal of the defective mineralisation in bone takes several years and vitamin D therapy may be needed indefinitely.

• Paget's disease is not an uncommon incidental finding on X-rays. In the absence of pain or significant deformity, treatment is not indicated.

I will now...

Dr Valuri responds to the answers to his questions

• I will continue to look for secondary hyperparathyroidism in patients with CKD and note their increased risk of fragility fractures.

• I will be more alert to the risk of developing vitamin D deficiency in patients taking anticonvulsants such as phenytoin, and in young people with learning difficulties.

• I will consider checking serum alkaline phosphatase in patients with incidental Paget's disease on X-ray to assess disease activity.

Dr Madhu Valuri is a GP in Stockport, Cheshire

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