BONE-MINERAL DENSITY AND BONE TURNOVER IN ASTHMATICS TREATED WITH LONG-TERM INHALED OR ORAL GLUCOCORTICOIDS

Inhaled glucocorticoids are pivotal in maintenance therapy of chronic bronchial asthma; however, conflict exists over their effects on bone and mineral metabolism. We measured bone mineral density (BMD), bone t urnover markers, and adrenal steroid hormones in 53 patients (34 femal e, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of greater than or equal to 150 0 mu g/day for at least 12 months to determine pathogenetic mechanisms of bone loss. To account for the effect of prior oral glucocorticoid exposure we divided patients into two groups: one with (OG) and the ot her without (IG) a past history of maintenance (> 1 month) oral glucoc orticoid therapy. Lumbar spine (LS) and proximal femur BMDs were simil ar to 1 SD lower in men and women taking OG or high-dose IG for chroni c bronchial asthma, potentially equivalent to a doubling of the risk o f fracture at these sites. Prior exposure to OG in women was also asso ciated with lower LS and proximal femur BMDs, while men were more sens itive to the adverse effects of IG on LS and Ward's triangle BMDs, Bon e formation markers were decreased; however, bone resorption marker co ncentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both t otal duration of OG and biochemical bone turnover marker concentration s were negatively related to proximal femur and rib BMDs and total bod y bone mineral content, but not to LS BMD, These were stronger for bon e resorption markers. Uncoupling of ongoing normal bone resorption fro m suppressed bone formation may therefore contribute to glucocorticoid -associated bone loss in asthma, Adrenal androgen suppression may also increase the susceptibility of postmenopausal women in particular to bone loss with OG, Although the effects of high-dose IG on BMD are ass ociated with lower LS BMD in men, this observation should now be inves tigated further in prospective studies.