Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures
Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures
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DOI：
10.1001/jamadermatol.2020.4968
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发表时间：
2021-01-20
期刊：
影响因子：
10.9
通讯作者：
Thyssen, Jacob P.
中科院分区：
文献类型：
--
作者：
Egeberg, Alexander;Schwarz, Peter;Thyssen, Jacob P.
局部使用皮质类固醇是否会引起全身不良事件，如使用全身性皮质类固醇时所见的不良事件？在一项对723251名强效或非常强效外用皮质类固醇使用者的队列研究中，这些药物的使用与骨质疏松症和严重骨质疏松性骨折的风险增加相关，且剂量-反应与累积使用相关。意义基于这些发现，临床医生可能需要考虑对需要长时间对大体表进行强效抗炎治疗以限制骨质疏松症风险的患者使用其他不使用皮质类固醇的治疗方案。这项全国性的队列研究考察了丹麦成人中强效和非常强效局部皮质类固醇的累积暴露与骨质疏松症和主要骨质疏松性骨折风险之间的关系。系统性和吸入性皮质类固醇在持续或大剂量使用时对骨重塑产生负面影响，并导致骨质疏松和骨折。然而，局部皮质类固醇（TCSs）应用后骨质疏松症和严重骨质疏松性骨折（MOF）的风险在很大程度上尚未被探索。目的探讨强效和极强效tcs的累积暴露与骨质疏松和MOF的关系。设计、环境和参与者：这项全国性的回顾性队列研究纳入了2003年1月1日至2017年12月31日期间接受强效或非常强效tcs治疗的723251名丹麦成年人。数据来自丹麦全国登记。填充处方数据以等效剂量转换为糠酸莫米松（1mg /g）。数据分析时间为2019年6月1日至8月31日。当患者的处方累积量相当于至少500克莫米松时，患者被视为暴露，以200至499克的处方作为参照组。主要结局和测量共同主要结局是骨质疏松症或MOF的诊断。采用Cox比例风险回归模型计算经年龄、性别、社会经济地位、药物使用和合并症调整后的风险比（hr）， ci为95%。结果共有723 251名成年人接受了相当于至少200 g莫米松的治疗，其中52.8%为女性，平均[SD]年龄52.8[19.2]岁。增加强效或非常强效tcs的使用与骨质疏松症和MOF的风险之间存在剂量-反应关联。例如，暴露于500至999 g时，MOF的hr为1.01 (95% CI, 0.99-1.03)，暴露于1000至1999 g时为1.05 (95% CI, 1.02-1.08)，暴露于2000至9999 g时为1.10 (95% CI, 1.07-1.13)，暴露于至少10,000 g时为1.27 （95% CI, 1.19-1.35）。累积TCS剂量每增加一倍，骨质疏松症和MOF的相对风险增加3%（两者的相对危险度为1.03 [95% CI, 1.02-1.04]）。骨质疏松症的总体人群归因风险为4.3% (95% CI, 2.7%- 3.8%)， MOF的总体人群归因风险为2.7% （95% CI, 1.7%-3.8%）。MOF暴露量至少为10,000 g时，增加1名患者（454人年）所需要的最低暴露量被观察到。结论和相关性这些发现表明，使用高累积量的强效或非常强效tcs与骨质疏松症和MOF的风险增加有关。
Question Does the use of topical corticosteroids cause systemic adverse events such as those seen with use of systemic corticosteroids? Findings In a cohort study of 723 251 users of potent or very potent topical corticosteroids, use of these drugs was associated with increased risk of osteoporosis and major osteoporotic fracture with a dose-response association for cumulative use. Meaning Based on these findings, clinicians may need to consider other corticosteroid-sparing therapeutic options for people requiring potent anti-inflammatory treatment on large body surfaces for prolonged periods to limit the risk of osteoporosis.This nationwide cohort study examines the association between cumulative exposure to potent and very potent topical corticosteroids and the risk of osteoporosis and major osteoporotic fracture among adults in Denmark.Importance Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk of osteoporosis and major osteoporotic fracture (MOF) after application of topical corticosteroids (TCSs) is largely unexplored. Objective To examine the association between cumulative exposure to potent and very potent TCSs and risk of osteoporosis and MOF. Design, Setting, and Participants This nationwide retrospective cohort study included 723 251 Danish adults treated with potent or very potent TCSs from January 1, 2003, to December 31, 2017. Data were obtained from Danish nationwide registries. Filled prescription data were converted in equipotent doses to mometasone furoate (1 mg/g). Data were analyzed from June 1 to August 31, 2019. Exposures Patients were considered exposed when they had filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone, using filled prescriptions of 200 to 499 g as the reference group. Main Outcomes and Measures The co-primary outcomes were a diagnosis of osteoporosis or MOF. Hazard ratios (HRs) adjusted for age, sex, socioeconomic status, medication use, and comorbidity were calculated with 95% CIs using Cox proportional hazards regression models. Results A total of 723 251 adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (52.8% women; mean [SD] age, 52.8 [19.2] years). Dose-response associations were found between increased use of potent or very potent TCSs and the risk of osteoporosis and MOF. For example, HRs of MOF were 1.01 (95% CI, 0.99-1.03) for exposure to 500 to 999 g, 1.05 (95% CI, 1.02-1.08) for exposure to 1000 to 1999 g, 1.10 (95% CI, 1.07-1.13) for exposure to 2000 to 9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to at least 10 000 g. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose (HR, 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for MOF. The lowest exposure needed for 1 additional patient to be harmed (454 person-years) was observed for MOF with exposure of at least 10 000 g. Conclusions and Relevance These findings demonstrate that use of high cumulative amounts of potent or very potent TCSs was associated with an increased risk of osteoporosis and MOF.