Long-Term Proton Pump Inhibitor Use Is Not Associated With Changes in Bone Strength and Structure

Targownik, Laura E.; Goertzen, Andrew L.; Luo, Yunhua; Leslie, William D.

doi:10.1038/ajg.2016.481

Cited by 66 publications

(47 citation statements)

References 43 publications

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“…Thus, based on our results, pharmacological mechanism between the association of PPI use and hip fracture seems to be unlikely. In addition, Targownik et al, found no changes in bone mineral density with long‐term PPI use.…”

Section: Discussionmentioning

confidence: 99%

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Proton pump inhibitor use and risk of hip fractures among community‐dwelling persons with Alzheimer's disease—a nested case‐control study

Torvinen-Kiiskinen

Tolppanen

Koponen

et al. 2018

Aliment Pharmacol Ther

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Summary Background Hip fractures are a major health concern among older persons with Alzheimer's disease, who usually use many concomitant drugs for several diseases. Evidence of the association between proton pump inhibitor use and risk of hip fracture is contradictory. Aim To investigate whether the long‐term use of proton pump inhibitor is associated with risk of hip fractures among community‐dwelling persons with Alzheimer's disease. Methods In this nested case‐control study, the nationwide MEDALZ data were utilised. Community‐dwelling persons with Alzheimer's disease who encountered incident hip fracture (N = 4818; mean age 84.1) were included as cases. Four controls were matched for each case at the date of hip fracture (N = 19 235; mean age 84.0). The association between hip fracture and duration of current PPI use (ongoing use during 0‐30 days before the index date), and cumulative duration of use during 10 years before was investigated with conditional logistic regression. Results Long‐term or cumulative proton pump inhibitor use was not associated with an increased risk of hip fracture. Current proton pump inhibitor use was associated with an increased risk of hip fracture (adjusted OR 1.12, 95% CI 1.03‐1.22). The risk was increased in short‐term current use (<1 year) (adjusted OR 1.23, 95% CI 1.10‐1.37). Conclusions The increased risk of hip fracture was evident only in short‐term proton pump inhibitor use, but no association was found for long‐term or cumulative use. Thus, our findings do not support previous assumptions that long‐term proton pump inhibitor use would be associated with an increased risk of hip fractures.

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Section: Discussionmentioning

confidence: 99%

“…It has been supposed that PPI use lead to bone loss and fractures by reducing calcium absorption . However, some studies have reported that PPI use has no effects on bone structure . Other mechanisms suggested are myopathy or vitamin B12 deficiency leading to injurious falls and fractures .…”

Section: Introductionmentioning

confidence: 99%

Proton pump inhibitor use and risk of hip fractures among community‐dwelling persons with Alzheimer's disease—a nested case‐control study

Torvinen-Kiiskinen

Tolppanen

Koponen

et al. 2018

Aliment Pharmacol Ther

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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

137

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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“…Maggio et al [53] assessed cortical and trabecular bone mineral density (BMD) and cross-sectional area and concluded that PPI users showed lower trabecular BMD than nonusers, even after age and gender adjustments. However, another study assessing not only areal BMD but also changes in bone structure which would predispose to fractures in the absence of changes in BMD concluded that long-term PPI use was not associated with changes in BMD or bone structure that would predispose to bone fractures [54]. Reviewing Hill criteria, the current evidence regarding bone fracture risk in PPI users has a weak strength, and only temporality and plausibility are present [7].…”

Section: Proposed Side Effects Of Ppismentioning

confidence: 99%

Proton Pump Inhibitors: Are They a Real Threat to the Patient?

Xavier¹,

Magalhães²,

Cotter³

2018

GE Port J Gastroenterol

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Background: Proton pump inhibitors are among the most frequently prescribed drugs in the world and are generally considered safe. However, there is growing concern regarding their safety. Summary: A nonsystematic review of the current literature was performed regarding proton pump inhibitors and their adverse effects. Proton pump inhibitors seem to be associated with fundic gland polyp development (without clinical relevance) and Clostridium difficile infection. Also, in cirrhotic patients, their prescription should be carefully reviewed. Regarding their association with other enteric infections, micronutrient deficiency, dementia, and chronic kidney disease, current evidence is still of low quality, and further studies are needed. Key Messages: Considering the current evidence, most patients with a clear clinical indication for proton pump inhibitor treatment should probably benefit from the maintenance of their treatment without significant adverse effects. However, higher-quality studies are needed to confirm or dismiss most of the proposed adverse effects.

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Long-Term Proton Pump Inhibitor Use Is Not Associated With Changes in Bone Strength and Structure

Abstract: Long-term PPI use is not associated with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture. These findings provide further evidence that the association between PPI use and fracture is not causal.

Cited by 66 publications

References 43 publications

Proton pump inhibitor use and risk of hip fractures among community‐dwelling persons with Alzheimer's disease—a nested case‐control study

Proton pump inhibitor use and risk of hip fractures among community‐dwelling persons with Alzheimer's disease—a nested case‐control study

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

Proton Pump Inhibitors: Are They a Real Threat to the Patient?

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