Egan J J, Maden C, Kalra S, Adams J E, Eastell R, Woodcock A A
North-West Lung Centre, Wythenshawe Hospital, Manchester, UK.
Eur Respir J. 1999 Jun;13(6):1267-75.
Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids have reduced bone mass. This prospective 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids. Patients (n = 33) (males aged 18-50 yrs, females aged 18-40 yrs) on inhaled corticosteroids 1,000-2,000 microg x day(-1), were randomized in a double-blind fashion to either fluticasone propionate (FP) 1,000 microg x day(-1) or beclomethasone dipropionate (BDP) 2,000 microg x day(-1). In parallel, three open control groups of the same age range were studied: asthmatics (n = 8) receiving low dose inhaled corticosteroids (< or =400 microg x day(-1)) (group A); chronic, severe asthmatics (n = 8) receiving oral corticosteroids (> or =10 mg x day(-1) (group B); and healthy untreated volunteers (n = 7) (group C). Bone densitometry scans (quantitative computed tomography (QCT) of spine; dual X-ray absorptiometry of spine, femoral neck, and single photon absorptiometry of forearm) were performed at baseline and after 6, 12 and 24 months of treatment. Biochemical bone marker measurements (serum osteocalcin, bone alkaline phosphatase, pro-collagen type 1 carboxy terminal propeptide, deoxypyridinoline and C-telopeptide of type 1 collagen) were collected every 3 months. Fifteen FP (mean age 36 yrs, six male) and 9 BDP patients (mean age 33 yrs, five male); completed the study. At 0 months, mean bone mineral density (BMD) was lower in patients receiving inhaled corticosteroids (both low dose and high dose) than in normal volunteers. In the FP-treated group, mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline, whereas there was some decline in the BDP-treated group. The treatment difference between FP and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months (p = 0.006) and 24 months (p = 0.004). This study suggests that over 24 months, changes in bone density are minimal in patients on high-dose inhaled corticosteroids.
横断面研究表明，接受高剂量吸入性糖皮质激素和间歇性口服糖皮质激素治疗的哮喘患者骨量减少。本前瞻性为期2年的研究旨在评估接受高剂量吸入性糖皮质激素治疗患者的骨密度变化。患者（n = 33）（男性年龄18 - 50岁，女性年龄18 - 40岁），吸入糖皮质激素剂量为1000 - 2000微克/天（-1），以双盲方式随机分为丙酸氟替卡松（FP）1000微克/天（-1）组或二丙酸倍氯米松（BDP）2000微克/天（-1）组。同时，对三个相同年龄范围的开放对照组进行了研究：接受低剂量吸入性糖皮质激素（≤400微克/天（-1））的哮喘患者（n = 8）（A组）；接受口服糖皮质激素（≥10毫克/天（-1））的慢性重症哮喘患者（n = 8）（B组）；以及健康未治疗志愿者（n = 7）（C组）。在基线以及治疗6、12和24个月后进行骨密度扫描（脊柱定量计算机断层扫描（QCT）；脊柱、股骨颈双能X线吸收法以及前臂单光子吸收法）。每3个月收集一次生化骨标志物测量数据（血清骨钙素、骨碱性磷酸酶、I型前胶原羧基末端前肽、脱氧吡啶啉和I型胶原C末端肽）。15名FP患者（平均年龄36岁，6名男性）和9名BDP患者（平均年龄33岁，5名男性）完成了研究。在0个月时，接受吸入性糖皮质激素治疗的患者（包括低剂量和高剂量）的平均骨矿物质密度（BMD）低于正常志愿者。在FP治疗组中，脊柱小梁骨BMD定量计算机断层扫描结果保持稳定，无下降迹象，而BDP治疗组则有一定下降。12个月（p = 0.006）和24个月（p = 0.004）后，FP和BDP之间的治疗差异在定量计算机断层扫描测量中具有统计学意义，有利于FP。这项研究表明，在24个月内，高剂量吸入性糖皮质激素治疗患者的骨密度变化极小。
