Faculty of Medicine, University of Medicine, Pharmacy, Science and Technology of Targu Mures, Targu Mures, Romania.
Institute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary.
Front Endocrinol (Lausanne). 2020 Nov 10;11:573976. doi: 10.3389/fendo.2020.573976. eCollection 2020.
Bisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can also contribute to low adherence in BP therapy and may necessitate a review by a gastroenterologist with or without gastroscopy.
Our meta-analysis aims to determine the risk of severe GI adverse events due to oral BP therapy in osteoporotic patients.
A systematic search was conducted in three databases up to September 2020 for randomized controlled trials (RCTs) detailing GI adverse events in adults with osteoporosis on BP compared to placebo. Risk ratios (RRs) with 95% confidence intervals (CI) were calculated for non-severe and severe adverse events indicating endoscopic procedure with the random-effects model. Statistical heterogeneity was assessed using chi and I statistics.
Forty-two RCTs with 39,047 patients with 9,999 non-severe and 1,503 severe GI adverse events were included. The incidence of non-severe and severe adverse events ranged between 0.3-54.9 and 0-10.3%, respectively. There was no difference between BP and control groups in terms of the risk of non-severe or severe side effects: RR=1.05 (CI: 0.98-1.12), I = 48.1%, and RR=1.01 (CI: 0.92-1.12), I = 0.0%, respectively. Subgroup analysis of the most commonly used BP, once-weekly alendronate 70 mg, revealed an association between bisphosphonates and the risk of non-severe GI adverse events, RR=1.16 (CI: 1.00-1.36), I = 40.7%, while the risk of severe GI side effects was not increased in this subgroup, RR=1.20 (CI: 0.83-1.74), I = 0.0%.
Our results show that bisphosphonates do not increase the risk of severe GI adverse events. However, the marked variability of the screening for side effects in the included studies, and the fact that in most of the studies GI diseases were exclusion criteria limits the strenght of evidence of our results. The conclusions drawn from the meta-analysis are therefore restricted to selected populations, and the results must be interpreted with caution.
双膦酸盐（BPs）是骨质疏松症的一线治疗药物。对于慢性、无症状的疾病，通常需要坚持治疗，但胃肠道（GI）副作用也会导致 BP 治疗的低依从性，可能需要由胃肠病学家进行审查，无论是否进行胃镜检查。
我们的荟萃分析旨在确定骨质疏松症患者口服 BP 治疗导致严重胃肠道不良事件的风险。
系统检索了三个数据库，截止到 2020 年 9 月，以确定成年人骨质疏松症患者接受 BP 治疗与安慰剂治疗相比的 GI 不良事件的随机对照试验（RCTs）。使用随机效应模型计算非严重和严重不良事件的风险比（RR），并伴有 95%置信区间（CI）。使用卡方和 I 统计量评估统计异质性。
共纳入 42 项 RCT，涉及 39047 名患者，999 例非严重 GI 不良事件和 1503 例严重 GI 不良事件。非严重和严重不良事件的发生率分别为 0.3-54.9%和 0-10.3%。BP 组和对照组在非严重或严重副作用的风险方面没有差异：RR=1.05（CI：0.98-1.12），I=48.1%，RR=1.01（CI：0.92-1.12），I=0.0%。对最常用的 BP（每周一次的阿伦膦酸钠 70mg）的亚组分析显示，双膦酸盐与非严重 GI 不良事件的风险之间存在关联，RR=1.16（CI：1.00-1.36），I=40.7%，而该亚组中严重 GI 副作用的风险没有增加，RR=1.20（CI：0.83-1.74），I=0.0%。
我们的结果表明，双膦酸盐不会增加严重胃肠道不良事件的风险。然而，纳入研究中对副作用的筛查存在显著差异，而且在大多数研究中，GI 疾病是排除标准，这限制了我们结果的证据强度。因此，从荟萃分析中得出的结论仅限于特定人群，并且必须谨慎解释结果。
