University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom.
J Clin Endocrinol Metab. 2012 Jun;97(6):1929-36. doi: 10.1210/jc.2011-3410. Epub 2012 Mar 21.
In asthmatic patients receiving long-term inhaled corticosteroid therapy, there are concerns regarding the potential for developing systemic adverse effects on bone metabolism, possibly even in the absence of adrenal suppression.
The aim of this study was to investigate whether exposure to inhaled ciclesonide at high vs. low doses over 1 yr causes any significant systemic adverse effect on sensitive biomarkers of bone turnover in asthmatic patients.
Post hoc analysis of stored samples was performed in a subgroup of patients from a prospective, randomized parallel group trial with 1 yr follow-up.
We conducted a primary care study in Tayside, Scotland.
A total of 164 mild-moderate persistent asthmatics aged 18-65 yr with evidence of airway hyperresponsiveness using mannitol bronchial challenge were enrolled into the original study. Of the 119 completed patients per protocol, 100 participants had bone marker samples available for analysis.
Ciclesonide was titrated to control persistent asthma against either mannitol bronchial challenge [airway hyperresponsiveness (AHR) strategy] or a control group (based on symptoms, reliever use, and pulmonary function) over 1 yr.
We measured markers of bone formation [amino-terminal propeptide of type I collagen (PINP), amino-terminal propeptide of type III collagen (PIIINP)], resorption [carboxy-terminal telopeptide of type I collagen (ICTP), type I collagen cross-linked C-telopeptide (CTx)], and adrenal suppression (overnight urinary cortisol/creatinine ratio) at 0 and 12 months.
Mean ciclesonide doses after 12 months were: AHR, 507 μg/d (n = 50); and controls, 202 μg/d (n = 50) (P < 0.00001). There were no significant differences between AHR and control groups either at baseline or after 12 months in PINP, PIIINP, ICTP, or CTx; or in ratios of bone turnover as PINP/ICTP, PIIINP/CTx, or overnight urinary cortisol/creatinine ratio.
Higher doses of inhaled ciclesonide do not adversely affect sensitive markers of bone turnover in persistent asthmatics over 12 months.
在接受长期吸入皮质类固醇治疗的哮喘患者中，人们担心可能会出现全身性的骨骼代谢不良反应，即使没有肾上腺抑制。
本研究旨在探讨在 1 年的时间内，高剂量和低剂量吸入昔萘酸沙美特罗是否会对哮喘患者的敏感骨转换生物标志物产生任何显著的全身性不良影响。
对一项前瞻性、随机平行组试验的存储样本进行了事后分析，该试验随访 1 年。
我们在苏格兰泰赛德的初级保健机构进行了这项研究。
共有 164 名年龄在 18-65 岁之间、有气道高反应性证据（使用甘露醇支气管激发试验）的轻中度持续性哮喘患者被纳入原始研究。在按方案完成的 119 名患者中，有 100 名患者有可供分析的骨标志物样本。
根据甘露醇支气管激发试验（气道高反应性策略）或对照组（基于症状、缓解药物使用和肺功能），将昔萘酸沙美特罗滴定至控制持续性哮喘，持续 1 年。
我们在 0 个月和 12 个月时测量了骨形成标志物[I 型胶原氨基端前肽（PINP）、III 型胶原氨基端前肽（PIIINP）]、骨吸收标志物[I 型胶原羧基端肽（ICTP）、I 型胶原交联 C 端肽（CTX）]和肾上腺抑制（ overnight urinary cortisol/creatinine ratio）。
12 个月时的平均昔萘酸沙美特罗剂量：气道高反应组 507μg/d（n=50）；对照组 202μg/d（n=50）（P<0.00001）。在基线或 12 个月时，气道高反应组和对照组在 PINP、PIIINP、ICTP 或 CTx 方面均无显著差异；或在骨转换的比值方面，如 PINP/ICTP、PIIINP/CTX 或 overnight urinary cortisol/creatinine ratio 也无差异。
在 12 个月的时间内，较高剂量的吸入昔萘酸沙美特罗不会对持续性哮喘患者的敏感骨转换标志物产生不良影响。
