Israel E, Banerjee T R, Fitzmaurice G M, Kotlov T V, LaHive K, LeBoff M S
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
N Engl J Med. 2001 Sep 27;345(13):941-7. doi: 10.1056/NEJMoa002304.
Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma.
We studied 109 premenopausal women, 18 to 45 years of age, who had asthma and no known conditions that cause bone loss and who were treated with inhaled triamcinolone acetonide (100 microg per puff). We measured bone density by dual-photon absorptiometry at base line, at six months, and at one, two, and three years. Serum osteocalcin and parathyroid hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured serially. We measured inhaled glucocorticoid use by means of monthly diaries, supported by the use of an automated actuator-monitoring device.
Inhaled glucocorticoid therapy was associated with a dose-related decline in bone density at both the total hip and the trochanter of 0.00044 g per square centimeter per puff per year of treatment (P= 0.01 and P=0.005, respectively). No dose-related effect was noted at the femoral neck or the spine. Even after the exclusion of all women who received oral or parenteral glucocorticoids at any time during the study, there was still an association between the decline in bone density and the number of puffs per year of use. Serum and urinary markers of bone turnover or adrenal function did not predict the degree of bone loss.
Inhaled glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal women.
吸入性糖皮质激素是哮喘患者长期治疗最常用的药物。吸入性糖皮质激素长期治疗是否像口服糖皮质激素治疗那样会降低骨量,这一点存在争议。在一项为期三年的前瞻性研究中,我们研究了哮喘绝经前女性吸入性糖皮质激素剂量与骨质流失率之间的关系。
我们研究了109名年龄在18至45岁之间的绝经前哮喘女性,她们没有已知的导致骨质流失的疾病,且接受吸入性曲安奈德(每喷100微克)治疗。我们通过双能X线吸收法在基线、6个月、1年、2年和3年时测量骨密度。连续测量血清骨钙素、甲状旁腺激素以及尿I型胶原交联N末端肽、皮质醇和钙排泄量。我们通过每月的日记记录吸入性糖皮质激素的使用情况,并借助自动喷雾器监测装置进行辅助记录。
吸入性糖皮质激素治疗与每年每喷每平方厘米全髋关节和大转子骨密度剂量相关的下降0.00044克有关(分别为P = 0.01和P = 0.005)。在股骨颈或脊柱处未观察到剂量相关效应。即使排除了在研究期间任何时候接受过口服或胃肠外糖皮质激素治疗的所有女性,骨密度下降与每年的喷数之间仍存在关联。骨转换或肾上腺功能的血清和尿标志物无法预测骨质流失程度。
吸入性糖皮质激素会导致绝经前女性髋部出现剂量相关的骨质流失。