Ebeling P R, Erbas B, Hopper J L, Wark J D, Rubinfeld A R
The Royal Melbourne Hospital, Department of Medicine, The University of Melbourne, Victoria, Australia.
J Bone Miner Res. 1998 Aug;13(8):1283-9. doi: 10.1359/jbmr.1998.13.8.1283.
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 turnover markers, and adrenal steroid hormones in 53 patients (34 female, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of > or = 1500 microg/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 other without (IG) a past history of maintenance (> 1 month) oral glucocorticoid therapy. Lumbar spine (LS) and proximal femur BMDs were approximately 1 SD lower in men and women taking OG or high-dose IG for chronic bronchial asthma, potentially equivalent to a doubling of the risk of fracture at these sites. Prior exposure to OG in women was also associated with lower LS and proximal femur BMDs, while men were more sensitive to the adverse effects of IG on LS and Ward's triangle BMDs. Bone formation markers were decreased; however, bone resorption marker concentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both total duration of OG and biochemical bone turnover marker concentrations were negatively related to proximal femur and rib BMDs and total body bone mineral content, but not to LS BMD. These were stronger for bone resorption markers. Uncoupling of ongoing normal bone resorption from 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 associated with lower LS BMD in men, this observation should now be investigated further in prospective studies.
吸入性糖皮质激素在慢性支气管哮喘的维持治疗中起着关键作用；然而，其对骨骼和矿物质代谢的影响存在争议。我们测量了53例慢性支气管哮喘患者（34例女性，19例男性）的骨密度（BMD）、骨转换标志物和肾上腺甾体激素，这些患者吸入倍氯米松或布地奈德剂量≥1500μg/天至少12个月，以确定骨质流失的发病机制。为了考虑既往口服糖皮质激素暴露的影响，我们将患者分为两组：一组有（OG），另一组无（IG）既往维持（>1个月）口服糖皮质激素治疗史。对于因慢性支气管哮喘服用OG或高剂量IG的男性和女性，腰椎（LS）和股骨近端BMD大约低1个标准差，这可能相当于这些部位骨折风险增加一倍。女性既往暴露于OG也与较低的LS和股骨近端BMD相关，而男性对IG对LS和沃德三角BMD的不良影响更敏感。骨形成标志物降低；然而，骨吸收标志物浓度正常。所有患者均有内源性糖皮质激素和肾上腺雄激素生成受抑制的证据。OG的总持续时间和生化骨转换标志物浓度均与股骨近端和肋骨BMD以及全身骨矿物质含量呈负相关，但与LS BMD无关。这些与骨吸收标志物的相关性更强。因此，正在进行的正常骨吸收与受抑制的骨形成解偶联可能导致哮喘中与糖皮质激素相关的骨质流失。肾上腺雄激素抑制也可能增加绝经后女性尤其是使用OG时骨质流失的易感性。尽管高剂量IG对BMD的影响与男性较低的LS BMD相关，但这一观察结果现在应在前瞻性研究中进一步调查。
