scholarly journals Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Silvia Irina Briganti ◽  
Anda Mihaela Naciu ◽  
Gaia Tabacco ◽  
Roberto Cesareo ◽  
Nicola Napoli ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Bone Health ◽  
Meta Analysis ◽  
Fragility Fractures ◽  
High Dose ◽  
Case Control Studies ◽  
Number Of Patients ◽  
Increased Risk

Despite the large number of patients worldwide being on proton pump inhibitors (PPIs) for acid-related gastrointestinal disorders, uncertainty remains over their long-term safety. Particularly, the potential side effects of these drugs on bone health have been evaluated in the last years. The purpose of our narrative review is to gather and discuss results of clinical studies focusing on the interactions between PPIs and fracture risk. Data generated mainly from nested case-control studies and meta-analysis suggest that long-term/high-dose PPIs users are characterized by an increased risk of fragility fractures, mainly hip fractures. However, in these studies, the PPIs-induced bone impairment is often not adjusted for different confounding variables that could potentially affect bone health, and exposure to PPIs was reported using medical prescriptions without adherence evaluation. The mechanisms of the PPI-related bone damage are still unclear, but impaired micronutrients absorption, hypergastrinemia, and increased secretion of histamine may play a role. Clinicians should pay attention when prescribing PPIs to subjects with a preexistent high risk of fractures and consider antiosteoporotic drugs to manage this additive effect on the bone. However, further studies are needed to clarify PPIs action on the bone.

scholarly journals Association between Proton Pump Inhibitors and Respiratory Infections: A Systematic Review and Meta-Analysis of Clinical Trials

2008 ◽  
Vol 22 (9) ◽  
pp. 761-766 ◽  
Author(s):  
Nabil Sultan ◽  
Jose Nazareno ◽  
James Gregor
Keyword(s):  
Respiratory Infection ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Respiratory Infections ◽  
Bacterial Colonization ◽  
Meta Analysis ◽  
Gastrointestinal Diseases ◽  
Controlled Trials ◽  
High Dose ◽  
Increased Risk

BACKGROUND: Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.OBJECTIVE: To examine the association between PPI treatment and respiratory infections.METHODS: A literature search was conducted using PubMed, MEDLINE and Cochrane databases of randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies that listed and quantified the specific adverse events of ‘respiratory infection’ or ‘upper respiratory infection’ (or equivalent), and compared their rates between PPIs and placebo were included. The χ2analysis was used to calculate the significance of association in individual studies and a meta-analysis of the selected studies was performed.RESULTS: Of 7457 studies initially identified and 70 relevant randomized, controlled trials (RCTs) selected, seven studies met the inclusion criteria. A total of 16 comparisons for χ2analysis were possible given the multiple dosage arms used in several studies. PPIs included in the studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than one-half of the studies showed a trend toward an association between PPI use and respiratory infections, although the majority of the studies failed to show a significant correlation. A single study using high-dose esomeprazole (40 mg) showed a significant association – 4.3% rate of respiratory infections in the active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed a trend toward an association between PPIs and respiratory infections, although it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17).CONCLUSION: Although a trend was evident in both a χ2analysis of individual studies and a meta-analysis, the present review and meta-analysis failed to show a conclusive association between PPIs and respiratory infections. Very few RCTs actively sought out respiratory infections, which excluded the majority of RCTs identified. A well-structured, placebo-controlled prospective study would be needed to determine whether a true association between PPIs and respiratory infections exists.

scholarly journals Proton Pump Inhibitors and Fracture Risk: A Review of Current Evidence and Mechanisms Involved

2019 ◽  
Vol 16 (9) ◽  
pp. 1571 ◽  
Author(s):  
Benjamin Ka Seng Thong ◽  
Soelaiman Ima-Nirwana ◽  
Kok-Yong Chin
Keyword(s):  
Fracture Risk ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Bone Health ◽  
Current Evidence ◽  
Mineral Absorption ◽  
Number Of Patients ◽  
The Relationship ◽  
Fracture Risks

The number of patients with gastroesophageal problems taking proton pump inhibitors (PPIs) is increasing. Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. This review aimed to investigate the longitudinal studies published in the last five years on the relationship between PPIs and fracture risk. The mechanism underlying this relationship was also explored. Overall, PPIs were positively associated with elevated fracture risk in multiple studies (n = 14), although some studies reported no significant relationship (n = 4). Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, mineral absorption, and muscle strength, contributing to increased fracture risk among PPI users. As a conclusion, there is a potential relationship between PPIs and fracture risks. Therefore, patients on long-term PPI treatment should pay attention to bone health status and consider prophylaxis to decrease fracture risk.

scholarly journals Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia

2020 ◽  
Vol 32 (5) ◽  
pp. 292-299 ◽  
Author(s):  
Phung Anh Nguyen ◽  
Mohaimenul Islam ◽  
Cooper J Galvin ◽  
Chih-Cheng Chang ◽  
Soo Yeon An ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Observational Studies ◽  
Meta Analysis ◽  
Community Acquired Pneumonia ◽  
Cochrane Library ◽  
High Dose ◽  
Increased Risk

Abstract Purpose Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. Data sources A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. Study selection We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. Data extraction Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. Results of data synthesis Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30–2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22–2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3–6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22–3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83–3.66). Conclusion We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

scholarly journals Long-term proton pump inhibitor use and the incidence of gastric cancer: A systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
pp. 1-11
Author(s):  
Ju-Li Lin ◽  
Jian-Xian Lin ◽  
Chao-Hui Zheng ◽  
Jian-Wei Xie ◽  
Jia-bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Proton Pump Inhibitor ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Meta Analysis ◽  
Inclusion Criteria ◽  
Risk Ratios

Background: There are controverted whether the long-term use of proton pump inhibitors (PPI) will increase the risk of gastric cancer. We performed a meta-analysis to assess the risk of gastric cancer in PPI users compared with non-PPI users. Methods: The main inclusion criteria were original studies reporting the incidence of gastric cancer in PPI users compared with non-PPI users. Key outcomes were the risk ratios (RR) for gastric cancer in association with PPI users or non-PPI users. Results: We analyzed data from 8 studies, comprising more than 927,684 patients. The risk of gastric cancer in PPI users was significantly higher than in non-PPI users [RR= 2.10, 95% CI (1.17-3.97)]. The risk of gastric cancer was similar between the 2 groups when the duration was ≤1 year [RR= 2.18, 95% CI (0.66-7.11)]. While the risk of gastric cancer for PPI users was higher than in non-PPI users when the duration was between 1-3 years, ≥1 year, ≥3 years and ≥5 years. The risk of non-cardiac gastric cancer for PPI users was higher than for non-PPI users [RR= 2.66, 95% CI (1.66 -4.27)], and the risk of non-cardiac gastric cancer for PPI users was higher than for non-PPI users when the duration ≥1 year [RR= 1.99, 95% CI (1.03-3.83)], but the risk for cardiac gastric cancer was similar between the 2 groups [RR= 1.86, 95% CI (0.71-4.89)]. Conclusions: We found the long-term use of PPI (duration ≥1 year) was significantly associated with a higher risk of non-cardiac gastric cancer.

scholarly journals Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence

2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Randomized Clinical Trials ◽  
Bacterial Overgrowth ◽  
Current Evidence ◽  
Neoplastic Progression ◽  
Increased Risk ◽  
H Pylori

Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual’s risk–benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.

Proton Pump Inhibitors and Dabigatran Therapy: Impact on Gastric Bleeding and Dabigatran Plasma Levels

2019 ◽  
Vol 45 (08) ◽  
pp. 846-850 ◽  
Author(s):  
Tomáš Bolek ◽  
Matej Samoš ◽  
Ingrid Škorňová ◽  
Peter Galajda ◽  
Ján Staško ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Levels ◽  
Thrombin Inhibitor ◽  
Gi Bleeding ◽  
Gastric Bleeding ◽  
Increased Risk ◽  
The Impact ◽  
Dabigatran Therapy

AbstractDabigatran etexilate, a direct thrombin inhibitor, is now frequently used for long-term pharmacological prevention of stroke or systemic embolism in patients with atrial fibrillation. However, such long-term dabigatran therapy (DT) significantly increases the risk of upper gastrointestinal (GI) bleeding. This increased risk of gastric bleeds might be reduced with gastroprotective agents, such as proton pump inhibitors (PPIs). PPIs coadministrated with dabigatran reduce the risk of upper GI bleeding in patients on long-term oral DT. Nevertheless, there is heated discussion regarding interactions between PPI and dabigatran that lead to decreases in dabigatran plasma levels. This article reviews up to date data about the risk of gastric bleeding on dabigatran, the impact of PPI on the reduction of gastric bleeding, and the interaction between PPI and dabigatran leading to decreased dabigatran plasma levels.

Proton pump inhibitors and upper gastrointestinal cancers

2019 ◽  
Vol 12 (9) ◽  
pp. 526-530
Author(s):  
Monica Kumar
Keyword(s):  
Gastric Cancer ◽  
General Practice ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cost Effective ◽  
Gastrointestinal Cancers ◽  
Increased Risk ◽  
The Uk ◽  
Upper Gastrointestinal

Proton pump inhibitors (PPIs) were introduced in the 1980s. They are now one of the most commonly prescribed drugs in general practice. They are cost-effective when used correctly; however, PPIs are often used beyond accepted clinical indications. Recent published studies performed outside the UK have suggested that adverse effects are associated with long-term use of PPIs; in particular, an increased risk of gastric cancer. This article will aim to systematically assess the evidence and discuss its application to our clinical practice.

scholarly journals Long Term Use of Proton Pump Inhibitors: Where to Draw the Line

2018 ◽  
Vol 1 (1) ◽  
pp. 20-35
Author(s):  
M. Manzurul Haque
Keyword(s):  
Adverse Effects ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Community Acquired Pneumonia ◽  
Ulcer Disease ◽  
Increased Risk ◽  
Prospective Trials ◽  
Evidence Based Therapy ◽  
Clostridium Difficile Associated Diarrhea

Proton pump inhibitors are the leading evidence-based therapy for acid related upper gastrointestinal disorders including dyspepsia, GERD and peptic ulcer disease. These are among the most frequently prescribed drugs globally. However, PPIs have been subjected to studies and have been associated with increased risk of adverse effects like Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fracture, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia etc. In this review the recent literature regarding these adverse effects and their association with long-term proton pump inhibitor treatment is discussed. The objective of this review is to analyse the potential adverse effects of long-term PPI use and summarize the clinical implications. We documented a considerable increase in the use of PPIs over the last decade. This increase is due to over-prescription and use of PPIs for inappropriate indications. On the other hand, some patients may have had PPI therapy discontinued abruptly or inappropriately due to safety concerns. However the patients with a proven indication for a PPI should continue to receive it in the lowest effective dose for a shortest possible time. Finally, in most cases and based on the available evidence, PPIs benefits seem to outweigh potential adverse effects. Large randomized prospective trials are required to more firmly establish direct cause and effect relationships between PPIs and adverse events.

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