A large volume spacer significantly reduces the effect of inhaled steroids on bone formation.

Inhaled steroids are increasingly advocated as first line treatment for mild asthma. Some studies suggest that inhaled steroids suppress bone formation as reflected by a fall in plasma osteocalcin. Spacers have been shown to increase the proportion of inhaled aerosol that is deposited in the lungs and to reduce the amount swallowed. We measured plasma osteocalcin levels to determine the effect on bone formation of inhaled beclomethasone dipropionate (BDP) with and without a 750 ml spacer in a double-blind, randomised, placebo-controlled, cross-over study. Twenty-six healthy male volunteers took BDP 500 micrograms (two puffs of Becloforte) together with two puffs of placebo, inhaled twice daily for seven days. One inhaler was taken directly while the other was inhaled through a 750 ml spacer. After a two week washout period, the inhalers were exchanged so that BDP was taken by the alternate route for a further seven days. Fasting plasma osteocalcin levels were measured at 09.00 h before and at the end of each week. After a week of BDP taken directly (without a spacer), osteocalcin levels fell from 11.8 (SEM 0.6) ng/ml to 9.5 (SEM 0.5) ng/ml (p < 0.001). After a week of BDP taken through a spacer, osteocalcin levels fell from 12.1 (SEM 0.5) ng/ml to 11.1 (SEM 0.5) ng/ml (p < 0.001). The fall in osteocalcin when a spacer was used was significantly less than when BDP was taken directly (p < 0.005). This is likely to be because the systemic effects on bone are caused by swallowed rather than inhaled BDP, and this is limited by the use of a spacer. Spacers should be more widely prescribed with inhaled steroids. Further prospective studies are indicated to evaluate whether spacers protect bone mass.

Urine-free cortisol excretion: evidence of sex-dependence.

Measurement of urine-free (unconjugated) cortisol (UFC) excretion is widely used in the investigation of hypercortisolaemia. We have measured 24 h UFC excretion in normal healthy individuals using a radioimmunoassay (RIA) method claimed to be suitable for unextracted urine. Significantly higher rates of excretion were found in a group of 15 men compared with a group of 18 women, with median values of 230 (range 145-334) and 149 (range 67-315) nmol/24 h, respectively (P < 0.005). This method was used to reanalyse the urine samples after extraction with dichloromethane. Although values were significantly lower than those found with unextracted urine (P < 0.001), the male:female difference remained with median values of 140 (range 96-295) and 112 (range 29-196) nmol/24 h, respectively (P < 0.02). Rates of UFC excretion were measured on the same dichloromethane-extracted urine samples using a second, different RIA, which again demonstrated the male:female difference with median values of 151 (range 116-302) and 109 (range 36-205) nmol/24 h, respectively (P < 0.001). There was no significant difference between these values and those obtained with extracted urine in the first assay. The higher rates of UFC excretion in men compared to women does not appear to be due to the presence of interfering compounds since the difference is also present using extracted urine samples and with two methods using different antibodies. These results should be borne in mind by laboratories when interpreting UFC results.