Proton pump inhibitors and osteoporosis

Andersen, Birgit; Johansen, Per B.; Abrahamsen, Bo

doi:10.1097/bor.0000000000000291

Cited by 76 publications

(48 citation statements)

References 40 publications

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“…Proton pump inhibitors are regularly used to treat patients suffering from upper gastrointestinal disorders. However, proton pump inhibitors increase the risk for osteoporotic fractures, which is reversed within 1 year of withdrawing from the therapy . Currently, there are no studies clarifying their mechanisms of bone loss …”

Section: Prescription Drugs Impact On Osteoporosis Pathwaysmentioning

confidence: 99%

Novel insights into the complex architecture of osteoporosis molecular genetics

Saad

2019

Annals of the New York Academy of Sciences

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Osteoporosis is a prevalent osteodegenerative disease and silent killer linked to a decrease in bone mass and decline of bone microarchitecture, due to impaired bone matrix mineralization, raising the risk of fracture. Nevertheless, the process of bone matrix mineralization is still an unsolved mystery. Osteoporosis is a polygenic disorder associated with genetic and environmental risk factors; however, the majority of genes associated with osteoporosis remain largely unknown. Several signaling pathways regulate bone mass; therefore, dysregulation of a single signaling pathway leads to metabolic bone disease owing to high or low bone mass. Parathyroid hormone, core‐binding factor α‐1 (Cbfa1), Wnt/β‐catenin, the receptor activator of the nuclear factor kappa‐B (NF‐κB) ligand (RANKL), myostatin, and osteogenic exercise signaling pathways play pivotal roles in the regulation of bone mass. The myostatin signaling pathway increases bone resorption by activating the RANKL signaling pathway, whereas osteogenic exercise inhibits myostatin and sclerostin while inducing irisin that consequentially activates the Cbfa1 and Wnt/β‐catenin bone formation pathways. The aims of this review are to summarize what is known about osteoporosis‐related signaling pathways; define the role of these pathways in osteoporosis drug discovery; focus light on the link between bone, muscle, pancreas, and adipose integrative physiology and osteoporosis; and underline the emerging role of osteogenic exercise in the prevention of, and care for, osteoporosis, obesity, and diabetes.

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Section: Prescription Drugs Impact On Osteoporosis Pathwaysmentioning

confidence: 99%

Novel insights into the complex architecture of osteoporosis molecular genetics

Saad

2019

Annals of the New York Academy of Sciences

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“…Second, it has been suggested that patients using PPI increase the risk of developing various infections . Third, it has been found that PPIs interfere with the absorption and metabolism of certain vitamins and minerals, especially B12, iron and calcium . Fourth, it has been shown that PPI has adverse effects on the absorption and metabolism of some drugs .…”

Section: Discussionmentioning

confidence: 99%

“…[66][67][68] Third, it has been found that PPIs interfere with the absorption and metabolism of certain vitamins and minerals, especially B12, iron and calcium. [69][70][71] Fourth, it has been shown that PPI has adverse effects on the absorption and metabolism of some drugs. [72][73][74] Finally, apart from these, it has been identified several side effects of PPIs, such as dementia, [75] coeliac diseases, [76] microscopic colitis, [77] chronic kidney disease, [78] myocardial infarction [79] and stroke.…”

Section: Discussionmentioning

confidence: 99%

A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors

Türkeş

2019

Journal of Pharmacy and Pharmacology

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Objectives Proton‐pump inhibitors (PPIs) are drugs commonly utilized by about 7% of adults in the world. Recent researches have shown that there are countless and severe side effects of these drugs. This situation has raised concern among clinicians and patients alike. The purpose of this study is to contribute the novel drug discovery and development technology and toxicology field by researching interactions of PPIs on paraoxonase 1. Methods In this study, the paraoxonase 1 enzyme was purified from human serum by using rapid and straightforward chromatographic techniques. Subsequently, the inhibition effects of pantoprazole, omeprazole, and esomeprazole, PPIs, were investigated on paraoxonase 1. Besides, molecular docking studies were performed to unravel the binding mechanism between the enzyme and drugs. Key findings All drugs showed potent inhibitory activities. IC50 of the drugs values were 54.780 ± 0.524, 86.470 ± 0.818 and 93.390 ± 0.885 mm and Ki constants were found as 39.895 ± 0.005 mm, 70.112 ± 0.010 mm and 78.868 ± 0.008 mm, respectively. The binding scores observed in silico studies were found to agree with the obtained from in‐vitro experimental results. Conclusions We observed that the drugs decreased PON1 activity at low concentrations. The results show that adjusting the dosages of these medications is a crucial case for each patient. The physicians should more carefully interpret whether there is an essential indication before prescribing PPIs and, if there is, to approve the proper dosing for the situation.

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“…Additionally, it has been argued that hypergastrinaemia may induce secondary hyperparathyroidism [28] that could lead to subsequent bone mineral loss. Observational studies and metaanalyses of observational studies have demonstrated an association between PPI use and bone fractures [29][30][31][32]; however, the associations found are weak and conflicting as other studies have found that neither changes in bone mineral density, bone structure nor manifest osteoporosis have been proven related to PPI use [33,34].…”

Section: Infectionsmentioning

confidence: 99%

Side Effects of Long‐Term Proton Pump Inhibitor Use: A Review

Haastrup

Thompson

Søndergaard

et al. 2018

Basic Clin Pharma Tox

140

124

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Proton pump inhibitors (PPIs) are widely used, and concerns about overuse have been raised. Therefore, side effects are important to be aware of and several suggested side effects of long-term use have been studied. In this MiniReview, we sum up the evidence of side effects related to long-term PPI treatment. Suspected side effects are mainly related to increased susceptibility to infections, secondary hypergastrinaemia, impeded absorption of micronutrients or idiosyncratic reactions. Most of the potential side effects have only been evaluated in observational studies demonstrating conflicting and weak associations with a substantial risk of confounding. However, a high probability of causality seems to be established for the side effects increased risk of gastrointestinal infections and rebound acid hypersecretion following discontinuation of treatment due to secondary hypergastrinaemia. The risk of side effects should not be a reason to withhold PPIs from patients with a true indication, and worry about poorly proven side effects should not lead to unnecessary discontinuation. The most important safety issue regarding PPI therapy is to critically evaluate the indication when initiating treatment and reconsidering the indication in long-term-treated patients.

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Proton pump inhibitors and osteoporosis

Cited by 76 publications

References 40 publications

Novel insights into the complex architecture of osteoporosis molecular genetics

Novel insights into the complex architecture of osteoporosis molecular genetics

A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors

Side Effects of Long‐Term Proton Pump Inhibitor Use: A Review

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