Dataset Information

Proton-pump Inhibitor Use and Fracture Risk: An Updated Systematic Review and Meta-analysis.

ABSTRACT:

Background

This study's objective was to evaluate the association between proton-pump inhibitor (PPI) use and bone fracture incidence and bone mineral density (BMD) by meta-analyzing the estimates reported by epidemiological and cohort studies.

Methods

Data were acquired from studies identified after a literature search in electronic databases. Odds ratios (ORs), hazard ratios (HRs), and risk ratios (RRs) between PPI use and bone fracture incidence were pooled under the random effects model, and meta-analysis of standardized mean differences between PPI users and controls in cross-sectional values and BMD changes was conducted.

Results

Thirty-three studies fulfilled the eligibility criteria. These studies provided data from 2,714,502 individuals with a mean age of 66.91 years (95% confidence interval [CI], 63.37-70.46); 33.21% (95% CI, 30.44-35.99) were males and 64.61% (95% CI, 60.73-68.49) were females. Overall, fracture incidence was 22.04% (95% CI, 16.10-27.97) in PPI users and 15.57% (95% CI, 12.28-18.86) in controls. The overall effect size of the point estimate was 1.28 (95% CI, 1.22-1.35) between PPI use and bone fracture incidence. There was a trend towards increased fracture incidence from short duration use: OR 1.29 (95% CI, 1.19-1.40), medium duration use: OR 1.33 (95% CI, 1.12-1.55) and long duration use: OR 1.62 (95% CI, 1.33-1.90). There was no significant difference in the standardized mean differences between PPI users and controls, either in cross-sectional BMD values or in the BMD change observed in longitudinal studies.

Conclusions

Pooling of ORs, HRs, and RRs suggested that PPI use might increase fracture risk. However, there was no effect of PPI use on BMD.

SUBMITTER: Nassar Y

PROVIDER: S-EPMC6135649 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proton-pump Inhibitor Use and Fracture Risk: An Updated Systematic Review and Meta-analysis.

Nassar Yousef Y Richter Seth S

Journal of bone metabolism 20180831 3

<h4>Background</h4>This study's objective was to evaluate the association between proton-pump inhibitor (PPI) use and bone fracture incidence and bone mineral density (BMD) by meta-analyzing the estimates reported by epidemiological and cohort studies.<h4>Methods</h4>Data were acquired from studies identified after a literature search in electronic databases. Odds ratios (ORs), hazard ratios (HRs), and risk ratios (RRs) between PPI use and bone fracture incidence were pooled under the random eff ...[more]

PMID: 30237993

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Project description:ImportanceProton pump inhibitor (PPI) use has been linked to increased risk of fracture in adults. Despite a trend in prescription of PPIs in children, there is scarce evidence regarding this safety concern in pediatric patients.ObjectiveTo evaluate the association between PPI use and risk of fracture in children.DesignThis nationwide register-based cohort study included data from Sweden from July 2006 to December 2016. Children younger than 18 years who initiated PPI use were matched on propensity score and age with those who did not initiate PPI use.ExposureInitiation of PPI use.Main outcomes and measuresCox regression was adopted to estimate hazard ratios (HRs) for a first fracture of any type and 5 subtypes of fracture, with follow-up for up to 5 years. To address potential residual confounding, high-dimensional propensity score matching and a direct comparison with histamine-2 receptor antagonists were performed.ResultsThere were a total of 115?933 pairs of children included. During a mean (SD) of 2.2 (1.6) years of follow-up, 5354 and 4568 cases of any fracture occurred among those who initiated PPIs vs those who did not, respectively (20.2 vs 18.3 events per 1000 person-years; hazard ratio [HR], 1.11 [95% CI, 1.06-1.15]). Use of PPIs was associated with increased risk of upper-limb fracture (HR, 1.08 [95% CI, 1.03-1.13]), lower-limb fracture (HR, 1.19 [95% CI, 1.10-1.29]), and other fractures (HR, 1.51 [95% CI, 1.16-1.97]) but not head fracture (HR, 0.93 [95% CI, 0.76-1.13]) or spine fracture (HR, 1.31 [95% CI, 0.95-1.81]). The HRs for fracture according to cumulative duration of PPI use were 1.08 (95% CI, 1.03-1.13) for 30 days or less, 1.14 (95% CI, 1.09-1.20) for 31 to 364 days, and 1.34 (95% CI, 1.13-1.58) for 365 days or more. The association was consistent in most sensitivity analyses, including high-dimensional propensity score matching (HR, 1.10 [95% CI, 1.06-1.15]), although the analysis of PPI vs histamine-2 receptor antagonist did not reach statistical significance (HR, 1.06 [95% CI, 0.97-1.15]).Conclusions and relevanceIn this large pediatric cohort, PPI use was associated with a small but significant increased risk of any fracture. Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children.

Project description:Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use.To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding.Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews.Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours).Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present.The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%.The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes.Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.

Dataset Information

Proton-pump Inhibitor Use and Fracture Risk: An Updated Systematic Review and Meta-analysis.

Background

Methods

Results

Conclusions

Publications

Proton-pump Inhibitor Use and Fracture Risk: An Updated Systematic Review and Meta-analysis.

Similar Datasets

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