GlaxoSmithKline, Research Triangle Park, NC, USA.
Phys Sportsmed. 2010 Dec;38(4):19-27. doi: 10.3810/psm.2010.12.1821.
There has been inconsistent evidence on the association between use of inhaled corticosteroids (ICS) and increased risk of nonvertebral fractures in patients with asthma or chronic obstructive pulmonary disease (COPD). In a large population-based study in the United Kingdom, we estimated the association between fluticasone propionate/salmeterol fixed-dose combination (FSC) and other ICS use and nonvertebral fracture incidence among patients with COPD.
We identified a cohort of patients aged ≥ 45 years with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. We used a nested case-control design to estimate the odds of incident nonvertebral fractures associated with prior prescriptions of FSC and other ICS, applying conditional logistic regression and controlling for potential confounders. Exposure to FSC and other ICS was assessed by recency, duration, and number of prescriptions. Average daily dose was defined as low, medium, high, or very high using fluticasone propionate equivalents.
We identified 1523 nonvertebral fracture cases among 53 191 patients with COPD at risk in the cohort. Use of FSC in the year prior to the index date was associated with a statistically significant increase in the odds of nonvertebral fractures (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.07-1.47); however, there was no increase in the odds of nonvertebral fractures for other ICS use (OR, 1.12; 95% CI, 0.97-1.30). When examining results by the recent use of prescriptions, an exposure that occurred farther from the index date was associated with a significant increase in nonvertebral fracture (26-52 days prior OR, 1.36; 95% CI, 1.04-1.77; 53-365 days prior OR, 1.39; 95% CI, 1.07-1.78), whereas categories of more recent use (0-12 days prior or 13-25 days prior) were not associated with nonvertebral fractures relative to no FSC use. No pattern of association between increasing levels of FSC or other ICS average daily dose and increased odds of nonvertebral fracture was observed.
We did not observe a consistent association between prescriptions of FSC or other ICS in terms of recent use or average daily dose in the prior year and increases in the odds of nonvertebral fractures in patients with COPD, although ever use of FSC was associated with a slight elevation in the odds.
在哮喘或慢性阻塞性肺疾病（COPD）患者中，使用吸入性皮质类固醇（ICS）与非椎体骨折风险增加之间的关联存在不一致的证据。在英国一项大型基于人群的研究中，我们评估了丙酸氟替卡松/沙美特罗固定剂量组合（FSC）与其他 ICS 使用与 COPD 患者非椎体骨折发生率之间的关系。
我们在 2003 年至 2006 年期间，在普通实践研究数据库（GPRD）中确定了一个年龄≥45 岁的 COPD 患者队列。我们使用嵌套病例对照设计来估计与 FSC 和其他 ICS 之前处方相关的非椎体骨折发生率的可能性，应用条件逻辑回归并控制潜在的混杂因素。通过最近、持续时间和处方数量评估 FSC 和其他 ICS 的暴露情况。使用丙酸氟替卡松等效物定义低、中、高或非常高的平均日剂量。
我们在高危队列中的 53191 名 COPD 患者中确定了 1523 例非椎体骨折病例。在索引日期前一年使用 FSC 与非椎体骨折几率的统计学显著增加相关（比值比[OR]，1.25；95%置信区间[CI]，1.07-1.47）；然而，其他 ICS 使用与非椎体骨折几率的增加无关（OR，1.12；95%CI，0.97-1.30）。当按最近处方的使用情况检查结果时，与索引日期越远的暴露与非椎体骨折的显著增加相关（26-52 天前 OR，1.36；95%CI，1.04-1.77；53-365 天前 OR，1.39；95%CI，1.07-1.78），而更近的使用类别（0-12 天前或 13-25 天前）与无 FSC 使用相比，与非椎体骨折无关。未观察到 FSC 或其他 ICS 平均日剂量与非椎体骨折几率增加之间与最近使用或前一年平均日剂量相关的一致关联。
我们没有观察到 COPD 患者中 FSC 或其他 ICS 处方在最近使用或前一年平均日剂量方面与非椎体骨折几率增加之间的一致关联，尽管 FSC 的使用与几率的轻微升高有关。
