High cumulative doses of inhaled steroids reduce bone density at the spine and femur, which may predispose patients to osteoporosis, according to Dr Conroy Wong (division of respiratory medicine, City hospital, Nottingham) and colleagues (Lancet 2000;355:1399).
The researchers conducted a survey of 196 patients, aged 20 to 40, with mild asthma who had had little previous exposure to oral, nasal, dermal or parenteral steroids. The median duration of treatment with an inhaled steroid was six years (range 0.5-24) and the median cumulative dose was 876mg (range 88-4,380). They found a "clear relationship" between the cumulative inhaled steroid dose and a reduction in bone density at the lumbar spine and proximal femur. The mean decrease associated with a doubling in the cumulative dose of inhaled steroid was 0.16 and 0.14 standard deviations (SDs) at the spine and femoral neck, respectively.
This would mean that the bone density of a patient who had taken 2,000µg daily of inhaled steroid for seven years would be one SD lower than that of a patient who had taken 200µg daily for one year, the researchers say. Over many years, this might translate into clinically important effects, as a one SD fall in bone density has been associated with a doubling of fracture risk in older women, they explain. Given the widespread use of inhaled steroids, a small increase in the risk of osteoporotic fracture would have substantial implications in public health terms, they add.
Dr Wong and colleagues say that inhaled steroids are "clearly highly effective" at controlling asthma and that this must be taken into account. However, they conclude that patients who need long-term, high-dose inhaled steroids may need prophylactic measures against osteoporosis.
The findings predominantly reflect the effects of inhaled beclomethasone, as 80 per cent of the subjects were using this steroid. The size of the effect may differ with other inhaled steroids, the researchers suggest.
Dr Philip Sambrook (Institute of Bone and Joint Research, University of Sydney, Australia) comments in an editorial (ibid, p1385) that confounding factors, such as previous use of steroids, age and asthma itself, were minimised. He compares the decrease of one SD in bone density with smoking 20 cigarettes a day for 10 years, which he says only produces a reduction of 0.2 SD. "Patients who take cumulative doses of 5,000mg should be monitored by bone densitometry and considered for active intervention to reduce the risk of osteoporotic fracture in later life", he says.
A spokesman for Glaxo Wellcome, the UK manufacturer of Becotide, told The Journal on May 3 that it was recognised that high dose inhaled steroids as a class might have an effect on bone mineral density, particularly if used for long periods. It was, therefore, important to use the lowest dose at which asthma symptoms were controlled. However, it was also recognised that the risk was lower than with oral steroids, he added.