Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Osteoporos Int. 2013 Sep;24(9):2493-8. doi: 10.1007/s00198-013-2352-3. Epub 2013 Apr 10.
Although systemic glucocorticoids are commonly used, it is difficult to obtain accurate exposure history. In 50,000 patients, we confirmed that glucocorticoids were associated with reductions in bone mineral density (BMD) and increases in fracture and documented that recent and prolonged durations of exposure were particularly associated with adverse events-dose information did not improve risk prediction.
Systemic glucocorticoid use, defined as ever having taken supra-physiologic doses for 90-days or more, is a risk factor for low BMD and fractures. This definition does not distinguish recent (vs remote) exposure.
Within a population-based clinical BMD registry in Manitoba, Canada, we identified all adults over age 40 years tested between 1998 and 2007 and then undertook a cohort study. We identified all oral glucocorticoid dispensations from 1995 to 2009 and stratified exposure by timing ("recent" if within 12 months vs "remote") and duration (short [<90 days] vs prolonged [≥90 days]). Osteoporosis-related risk factors and treatments and major fractures were obtained using administrative health data.
A total of 12,818 of 52,070 (25%) subjects had used glucocorticoids prior to BMD testing; the most common exposure was remote short (n = 6453) vs recent prolonged (n = 2896) vs recent short (n = 2644) vs remote prolonged (n = 825). Compared to 39,252 never-users, only recent prolonged glucocorticoid use was significantly associated with femoral neck T-score (ANCOVA-adjusted difference -0.13, 95% CI -0.16 to -0.10, p < 0.001). There were 2,842 major (566 hip) fractures over median 5-year follow-up. Compared with never-users, only recent prolonged glucocorticoid use was significantly associated with BMD-independent increases in risk of incident major fracture (5.4 vs 7.7%, adjusted HR 1.25, 95% CI 1.07-1.45, p = 0.004) and hip fracture (1.1 vs 1.8%, adjusted HR 1.61, 95% CI 1.18-2.20, p = 0.003).
Recent and prolonged glucocorticoid use (but neither remote nor recent short courses) was independently associated with reduced BMD and increased risk of fractures. These findings should permit clinicians to identify a high-risk group of patients that might benefit from osteoporosis prevention.
虽然全身糖皮质激素的应用较为常见，但准确获取其使用史却较为困难。在 5 万名患者中，我们证实糖皮质激素与骨密度（BMD）降低、骨折风险增加相关，并证明近期和长期暴露尤其与不良事件相关——而药物剂量信息并不能改善风险预测。
全身糖皮质激素的使用，定义为曾经接受过超过生理剂量 90 天或更长时间的治疗，是低 BMD 和骨折的危险因素。该定义并未区分近期（vs 远期）暴露。
在加拿大马尼托巴省基于人群的临床 BMD 注册中心内，我们纳入了所有在 1998 年至 2007 年期间进行测试的 40 岁以上成年人，并进行了队列研究。我们从 1995 年至 2009 年获得了所有口服糖皮质激素的处方信息，并根据时间（在 12 个月内为“近期”，超过 12 个月为“远期”）和持续时间（＜90 天为“短期”，≥90 天为“长期”）分层暴露情况。我们使用行政健康数据获得了骨质疏松相关风险因素和治疗方法以及主要骨折情况。
在 52070 名受试者中，共有 12818 名（25%）在 BMD 检测前曾使用过糖皮质激素；最常见的暴露是远期短期（n=6453）vs 近期长期（n=2896）vs 近期短期（n=2644）vs 远期长期（n=825）。与 39252 名从未使用者相比，仅有近期长期糖皮质激素的使用与股骨颈 T 评分显著相关（ANCOVA 调整后差值-0.13，95%CI-0.16 至-0.10，p<0.001）。在中位 5 年随访期间共发生了 2842 例主要（566 例髋部）骨折。与从未使用者相比，仅有近期长期糖皮质激素的使用与 BMD 无关的骨折风险增加显著相关（发生率分别为 5.4% vs 7.7%，调整后 HR 1.25，95%CI 1.07-1.45，p=0.004）和髋部骨折（发生率分别为 1.1% vs 1.8%，调整后 HR 1.61，95%CI 1.18-2.20，p=0.003）。
近期和长期糖皮质激素的使用（而非远期或近期短期使用）与 BMD 降低和骨折风险增加独立相关。这些发现应该可以帮助临床医生识别出一个可能受益于骨质疏松预防的高风险患者群体。
