Editorials

Prevention of corticosteroid induced osteoporosis

Should be easier if doctors follow the recent guidelines 

Corticosteroid induced osteoporosis has presented a challenge to clinicians for many years. Bone loss during corticosteroid treatment is mediated by inhibition of gonadal and adrenal steroid production, leading to hypogonadism and a direct negative effect on calcium absorption and osteoblast function.¹ Epidemiological data suggest that corticosteroid treatment doubles the risk of fractures of the hip and distal radius and at least quadruples the risk of vertebral fracture. How can this damage be limited?

Corticosteroids are widely used, especially for rheumatoid arthritis, polymyalgia rheumatica, and chronic obstructive pulmonary disease. A cross sectional study in Nottinghamshire in over 65 000 patients showed that 0.5% were taking oral corticosteroids.² Most were aged 60-80 years and the mean dose was 8 mg/day, with a median duration of treatment of three years. Only 14% of these patients had received preventive treatment for osteoporosis. If these data are extrapolated to the whole population, over 250 000 people in the United Kingdom are taking oral corticosteroids.

Monitoring bone loss has become easy now that bone mineral density can be measured with dual energy x ray absorptiometry. Nevertheless, many patients taking long term corticosteroids are not referred for bone mineral density measurement. Prevention and treatment of corticosteroid osteoporosis are feasible with hormones or bisphosphonates. Hormone replacement therapy increases bone mineral density in the lumbar spine in patients with corticosteroid osteoporosis.³ Testosterone has similar effects in men treated with corticosteroids.⁴ Bisphosphonates are very effective for the primary and secondary prevention of corticosteroid osteoporosis. Double blind studies have been performed with cyclical etidronate and alendronate showing positive effects on bone mineral density in the lumbar spine and hip and fewer vertebral fractures in postmenopausal women. ^{5 6} One concludes that it is not so much diagnostic technologies and effective treatment that are lacking as their implementation.

The publication of guidelines on preventing and managing corticosteroid induced osteoporosis should therefore be warmly welcomed.⁷ The guidelines have been developed by a consensus group which has also summarised the evidence on which the recommendations are based.⁸ The guidelines are concise and practical and do not recommend tests that are cumbersome and not widely available. They are directed at patients who use prednisolone (equivalent) 7.5 mg/day or more. The guidelines do not apply to inhaled corticosteroids or to patients with organ transplants.

The guidelines open with a grading of the evidence on which the recommendations are based. The recommendations are then presented as an algorithm, which is easy to use but also contains some ambiguities. General measures concerning lifestyle, calcium and vitamin D intake, and a review of corticosteroid therapy are recommended for all patients. The first dichotomy is the presence or absence of an osteoporotic fracture. The presence of an osteoporotic fracture should probably be interpreted liberally, including fractures of the vertebrae, hip, rib, distal radius, and humerus. Should spinal radiography be performed? The guidelines don't mention it, but spinal radiographs might be recommended in elderly patients, especially when they have back pain. When fractures are present the guidelines state that other causes of osteoporosis should be excluded and treatment started right away.

If there is no fracture, treatment is recommended in all patients aged over 65 years, those taking more than 15 mg/day of prednisolone, and others with strong risk factors (premature menopause, a low trauma fracture, family history, immobility, low body weight) or low bone mineral density. Given the characteristics of people treated with corticosteroids this means that three in every four patients should be treated.²

The treatment options are sex steroids, bisphosphonates, or calcitriol. In opting for bisphosphonates as the first choice the consensus group has made the right decision on the basis of evidence from randomised double blind controlled trials. The decision has probably been difficult since bisphosphonates are especially recommended for "those who are eugonadal or unable or unwilling to take hormone replacement therapy." All men and premenopausal women should be investigated for hypogonadism and, if this is confirmed, should be treated appropriately. However, the guidelines are ambiguous about hormone replacement therapy, which "should be offered to postmenopausal women." The evidence for hormone replacement therapy is less robust (comparative studies), making it an alternative only when bisphosphonates are not tolerated. In my opinion there is no reason to combine hormone replacement therapy and bisphosphonates unless the response to bisphosphonates is insufficient. When patients cannot tolerate bisphosphonates or there are concerns about safety (in younger patients) calcitriol may be considered. Here again the evidence is less robust. One randomised trial with calcitriol showed protection against bone loss in the spine but not in the hip.⁹ Monitoring of bone mineral density after one year's treatment is advised in all patients. This implies that a baseline bone mineral density should be obtained in all patients, although the algorithm does not actually state this.

When the patient is younger than 65 years, the prednisolone dose is less than 15 mg/day, and there are no strong risk factors, a bone mineral density measurement at baseline and at one year is advised. If significant bone loss occurs treatment should be started. The guidelines end with special recommendations for children.

The strength of these guidelines is that they state exactly what to do and who should do it. The doctor prescribing corticosteroids should play an active part from the startby instituting prophylactic treatment in most patients after investigations, including a bone mineral density measurement, or measuring bone mineral density at baseline and at one year in low risk patients.

How do the guidelines reach the general public and the patients? The National Osteoporosis Society will distribute the key messages widely. A suitable way to reach individual patients might be through pharmacies: every first prescription of corticosteroids could be accompanied by a leaflet on the risks of osteoporosis and the new guidelines. The initiative of these guidelines should be widely followed in other countries.

Paul Lips, Internist. 

Department of Endocrinology, Academic Hospital Vrije Universiteit, PO Box 7057, 1007 MB Amsterdam, Netherlands (P.Lips{at}azvu.nl)