Hanania N A, Chapman K R, Sturtridge W C, Szalai J P, Kesten S
Asthma Centre, Toronto Hospital, University of Toronto, Canada.
J Allergy Clin Immunol. 1995 Nov;96(5 Pt 1):571-9. doi: 10.1016/s0091-6749(95)70254-7.
Inhaled corticosteroids are being prescribed more commonly and in higher doses than previously in the management of asthma. Although these topically active compounds have less potential for systemic impact than oral steroids, biochemical markers suggest that they are not devoid of systemic side effects. We conducted this study to investigate the effect of commonly prescribed doses of inhaled steroids on bone density.
We studied 36 patients with asthma. Those in group A (n = 18) had been taking inhaled beclomethasone dipropionate or budesonide in a dosage of 800 micrograms or more per day for at least 1 year. Those in group B (n = 18) had used only bronchodilator therapy. Adrenal function was assessed by morning serum cortisol level and by short adrenocorticotropic hormone stimulation test. Bone turnover was assessed by measurement of serum osteocalcin, alkaline phosphatase, and urinary pyridinium cross-links. Bone mineral density was measured by dual-energy x-ray absorptiometry with a Hologic QDR-1000 densitometer (Hologic Inc., Waltham, Mass.).
Group A, mean age (SD) = 36.6 (8.4) years, had used inhaled corticosteroids at a mean dose of 1323 micrograms/day (range, 800 to 2000 micrograms/day) for a median duration of 24 months. Group B, mean age (SD) = 33.4 (8.1) years, had not been taking any form of steroid. Four patients from group A had suppressed morning serum cortisol; three of these had abnormal adrenocorticotropic hormone stimulation test results. All patients in group B had normal baseline adrenal function and an appropriate response to adrenocorticotropic hormone. Mean serum osteocalcin level in group A was significantly lower than that in group B (8.8 vs 14.2 ng/ml, p = 0.0003). Bone density measurements showed parallel changes: in group A the mean Z score (SD) of the femoral neck was -0.78 (1.02), significantly below predicted normal values (p = 0.0025). Mean Z scores of the lumbar spine and of femoral Ward's triangle were not significantly reduced. In group B the mean Z scores of the lumbar spine, femoral neck, and femoral Ward's triangle were all within normal limits. In group A the dose duration of inhaled corticosteroid therapy corrected for body mass index correlated negatively with bone density and adrenal function measurements.
We conclude that the regular use of conventional doses of inhaled corticosteroids by patients with asthma can suppress adrenal function and decrease bone density in a dose-related fashion.
与以往相比，吸入性糖皮质激素在哮喘治疗中的应用更为普遍，剂量也更高。尽管这些局部活性化合物产生全身影响的可能性低于口服类固醇，但生化指标表明它们并非没有全身副作用。我们开展这项研究以调查常用剂量的吸入性类固醇对骨密度的影响。
我们研究了36例哮喘患者。A组（n = 18）患者每天服用800微克或更高剂量的吸入性二丙酸倍氯米松或布地奈德至少1年。B组（n = 18）患者仅接受支气管扩张剂治疗。通过早晨血清皮质醇水平和短程促肾上腺皮质激素刺激试验评估肾上腺功能。通过测量血清骨钙素、碱性磷酸酶和尿吡啶交联物评估骨转换。使用Hologic QDR - 1000骨密度仪（Hologic公司，马萨诸塞州沃尔瑟姆）通过双能X线吸收法测量骨矿物质密度。
A组患者的平均年龄（标准差）为36.6（8.4）岁，吸入性糖皮质激素的平均剂量为1323微克/天（范围为800至2000微克/天），中位疗程为24个月。B组患者的平均年龄（标准差）为33.4（8.1）岁，未服用任何形式的类固醇。A组有4例患者早晨血清皮质醇受到抑制；其中3例促肾上腺皮质激素刺激试验结果异常。B组所有患者的肾上腺功能基线正常，对促肾上腺皮质激素反应正常。A组的平均血清骨钙素水平显著低于B组（8.8对14.2纳克/毫升，p = 0.0003）。骨密度测量结果显示出平行变化：A组股骨颈的平均Z值（标准差）为 - 0.78（1.02），显著低于预测的正常值（p = 0.0025）。腰椎和股骨Ward三角区的平均Z值没有显著降低。B组腰椎、股骨颈和股骨Ward三角区的平均Z值均在正常范围内。在A组中，经体重指数校正的吸入性糖皮质激素治疗的剂量疗程与骨密度和肾上腺功能测量值呈负相关。
我们得出结论，哮喘患者常规使用常规剂量的吸入性糖皮质激素可抑制肾上腺功能，并以剂量相关的方式降低骨密度。
