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使用口服泼尼松龙的老年患者中阿仑膦酸盐的使用与髋部骨折风险之间的关联

Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone.

作者信息

Axelsson Kristian F, Nilsson Anna G, Wedel Hans, Lundh Dan, Lorentzon Mattias

机构信息

Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden2Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden3Department of Endocrinology, Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

JAMA. 2017 Jul 11;318(2):146-155. doi: 10.1001/jama.2017.8040.

Abstract

IMPORTANCE

Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids.

OBJECTIVE

To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (≥5 mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014.

EXPOSURES

Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation.

MAIN OUTCOMES AND MEASURES

The primary outcome was incident hip fracture.

RESULTS

Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group.

CONCLUSIONS AND RELEVANCE

Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

摘要

重要性

口服糖皮质激素治疗会增加骨折风险,而对于阿仑膦酸钠在使用糖皮质激素的老年患者中预防髋部骨折疗效的证据尚不足。

目的

研究在使用口服泼尼松龙的老年患者中,阿仑膦酸钠治疗是否与髋部骨折风险降低及不良反应相关。

设计、设置和参与者:使用瑞典医疗机构全国数据库(N = 433195)进行回顾性队列研究,纳入65岁及以上接受健康评估(基线)的患者;确定1802例在口服泼尼松龙治疗至少3个月(≥5mg/d)后开具阿仑膦酸钠处方的患者。采用倾向评分匹配法从6076例服用相同剂量和治疗时间标准泼尼松龙的患者中选取1802例未使用阿仑膦酸钠的患者。随访时间为2008年1月至2014年12月。

暴露因素

阿仑膦酸钠使用与否;在开始使用泼尼松龙时,无患者曾服用过阿仑膦酸钠。

主要结局和测量指标

主要结局为新发髋部骨折。

结果

在纳入的3604例患者中,平均年龄为79.9(标准差,7.5)岁,2524例(70%)为女性。中位随访1.32年(四分位间距,0.57 - 2.34年)后,阿仑膦酸钠组有27例髋部骨折,未使用阿仑膦酸钠组有73例,对应发病率分别为每1000人年9.5例(95%置信区间,6.5 - 13.9)和27.2例(95%置信区间,21.6 - 34.2),绝对率差为 - 17.6(95%置信区间, - 24.8至 - 10.4)。在多变量调整的Cox模型中,使用阿仑膦酸钠与较低的髋部骨折风险相关(风险比,0.35;95%置信区间,0.22 - 0.54)。阿仑膦酸钠治疗与轻度上消化道症状风险增加无关(阿仑膦酸钠组与未使用阿仑膦酸钠组,每1000人年分别为15.6例[95%置信区间,11.6 - 21.0]和12.9例[95%置信区间,9.3 - 18.0];P = 0.40)或消化性溃疡无关(每1000人年分别为10.9例[95%置信区间,7.7 - 15.5]和11.4例[95%置信区间,8.0 - 16.2];P = 0.86)。每组均无药物性骨坏死新发病例,且每组仅1例股骨干骨折病例。

结论和相关性

在使用中至高剂量泼尼松龙的老年患者中,阿仑膦酸钠治疗在中位1.32年期间与显著较低的髋部骨折风险相关。尽管研究结果受观察性研究设计和事件数量较少的限制,但这些结果支持在该患者群体中使用阿仑膦酸钠。

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