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

Author(s):  
Benjamin Ka Seng Thong ◽  
Soelaiman Ima-Nirwana ◽  
Kok-Yong Chin

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Silvia Irina Briganti ◽  
Anda Mihaela Naciu ◽  
Gaia Tabacco ◽  
Roberto Cesareo ◽  
Nicola Napoli ◽  
...  

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.


2015 ◽  
Vol 9 (3) ◽  
pp. 287 ◽  
Author(s):  
Antonio Villa ◽  
Paolo Zanada ◽  
Adriana Pellegrino ◽  
Gabriella Nucera ◽  
Elena Martinoli ◽  
...  

Hypomagnesemia is defined by having a serum magnesium level of less than 1.7 mg/dL. The magnesium balance is tightly regulated by the concerted actions of the intestine, bone and kidneys. This balance can be disturbed by a wide variety of drugs. Recently, we observed a case of severe hypomagnesemia caused by proton pump inhibitor therapy. We conducted a retrospective study of an <em>intrahospital population</em> to evaluate the prevalence of hypomagnesemia and the relationship with associated drugs. Among 181 patients with hypomagnesemia only 29 were found to have hypomagnesemia with specific causes, such as chronic diarrhea, vomiting, and so on. In the remaining patients, 120 have taken proton pump inhibitors and/or diuretics and/or metformin. Clinicians should consider proton pump inhibitors as a possible causative agent when investigating hypomagnesemia and they should be especially attentive with patients who take proton pump inhibitors, especially in cases of long-term therapy (≥1 year) and/or concomitant administration of other agents that may lower magnesium levels (<em>e.g</em>., diuretics or metformin).


2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung

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.


2018 ◽  
Vol 40 (3) ◽  
pp. 301-306 ◽  
Author(s):  
Carine Franco Morschel ◽  
Denise Mafra ◽  
José Carlos Carraro Eduardo

ABSTRACT Proton pump inhibitors (PPIs) bind to enzyme H+/K+-ATPase and inhibit its activity in the stomach, thus decreasing the secretion of gastric acid. PPIs may trigger acute interstitial nephritis, a potentially severe adverse event commonly associated with acute kidney injury. Studies have found that prolonged use of PPIs may increase the risk of chronic kidney disease (CKD). The increase in prescription and inadequate use of this class of medication calls for studies on the effects of prolonged PPI therapy on renal function. Therefore, this review aimed to analyze recent studies on the matter and discuss the possible consequences of the long-term use of PPIs on renal function.


2019 ◽  
Vol 20 (21) ◽  
pp. 5469 ◽  
Author(s):  
Helgadottir ◽  
Bjornsson

Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.


PRiMER ◽  
2021 ◽  
Vol 5 ◽  
Author(s):  
Andrew Lai ◽  
Amy Odom ◽  
Steven E. Roskos ◽  
Julie P. Phillips

Introduction: Proton pump inhibitors (PPIs) are often prescribed beyond their medically-approved duration of use. Long-term PPI use has been linked with numerous adverse effects and contributes to polypharmacy. This study sought to understand the effect of evidence-based education to resident and faculty physicians on deprescribing inappropriate PPIs. We hypothesized that this educational intervention would result in fewer inappropriate PPI prescriptions. Methods: We performed a chart review on all adult patients in a family medicine residency program practice, identifying those inappropriately taking PPIs. All physicians in the practice participated in an educational intervention regarding deprescribing inappropriate PPIs and were given frequent reminders to continue their deprescribing efforts. We reviewed charts at the end of the study to identify patients with successful deprescribing attempts. Results: Of the 187 patients prescribed inappropriate PPIs in the study, 100 remained on PPIs at the end of the study (46.6% success rate). There was a significant decrease in the number of patients inappropriately prescribed PPIs by each physician over the course of the study, from a mean of 17.0 (beginning) to 9.1 (end). Conclusion: Physician education with reminders is an effective means of reducing the number of inappropriate PPIs prescribed in a family medicine residency practice. Future studies could investigate the effectiveness of educational interventions with other medication classes that are often prescribed inappropriately.


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