Proton pump inhibitors and fracture: they impair bone quality and increase fall risk?

Sugiyama, Toshihiro; Watarai, Keisuke; Oda, Takuji; Kim, Y. T.; Oda, Hiromi

doi:10.1007/s00198-016-3509-7

Cited by 10 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 46 ] Bone fragility depends not only on areal BMD but also on other factors including bone quality, which may be affected by other factors such as vitamin B12 levels and modulated skeletal fragility due to collagen cross-linking independent of areal BMD. [ 47 ]…”

Section: Discussionmentioning

confidence: 99%

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

Nassar

Richter

2018

J Bone Metab

View full text Add to dashboard Cite

BackgroundThis 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.MethodsData 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.ResultsThirty-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.ConclusionsPooling of ORs, HRs, and RRs suggested that PPI use might increase fracture risk. However, there was no effect of PPI use on BMD.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Nassar

Richter

2018

J Bone Metab

View full text Add to dashboard Cite

show abstract

“…Vitamin B12 deficiency can lead to an increase in osteoclastic activity, a decrease in osteoblastic activity, and homocysteinemia causing abnormal collagen cross-linking [ 11 ]. The deficiency of vitamin B12 can affect bone fragility through modulation of collagen cross-linking independently of areal BMD [ 41 , 42 ]. This increased bone fragility, along with increased fall risk in elderly patients with PPI use due to peripheral neuropathy caused by vitamin B12 deficiency, can contribute to increased fracture rates [ 42 , 43 ].…”

Section: Reviewmentioning

confidence: 99%

“…The deficiency of vitamin B12 can affect bone fragility through modulation of collagen cross-linking independently of areal BMD [ 41 , 42 ]. This increased bone fragility, along with increased fall risk in elderly patients with PPI use due to peripheral neuropathy caused by vitamin B12 deficiency, can contribute to increased fracture rates [ 42 , 43 ].…”

Section: Reviewmentioning

confidence: 99%

Establishing the Association Between Osteoporosis and Peptic Ulcer Disease: A Systematic Review

Selvin¹,

Thomas²,

Bikeyeva³

et al. 2022

Cureus

View full text Add to dashboard Cite

Osteoporosis is one of the most common metabolic bone diseases. Many studies were conducted to find the association between peptic ulcer disease (PUD), Helicobacter pylori infection, proton-pump inhibitor (PPI) use, and increased risk for fracture, but results remain ambiguous. We performed this systematic review to understand the association between PUD and osteoporosis. We comprehensively searched relevant articles on April 19, 2022, by exploring different databases including PubMed, PubMed Central (PMC), and Medline using relevant keywords. After applying inclusion and exclusion criteria and undergoing quality assessment, we retained 25 studies published in and after 2015. For our systematic review, we included a total of 5,600,636 participants. The studies included in our review demonstrated a significant association between PUD, H. pylori infection, and the risk of osteoporosis. Long-term PPI use was also found to be a risk factor for osteoporosis. Malabsorption of nutrients, increase in inflammatory cytokines, and alterations in hormone status were found to be the notable factors behind the association. Early management of H. pylori infection and cautious use of long-term PPIs may protect against osteoporosis. Further randomized controlled trials (RCTs) are necessary to establish a causal relationship.

show abstract

“…Proposed mechanisms include chronic PPI use leading to decreased intestinal absorption of calcium resulting in an increase in bone fracture rate; PPI-induced inhibitory effects on the vacuolar type of H + K + ATPase of osteoclasts leading to an increase in their activity; PPI-induced hypochlorhydria leading to hypergastrinemia, which in turn stimulates the development of parathyroid hyperplasia; PP-induced hypomagnesemia, which can contribute to altered bone metabolism and increased risk of bone fractures; and the hypergastrinemic stimulation of ECL hyperplasia resulting in an increased in histamine production, which can stimulate proliferation of osteoclasts resulting in increased bone absorption [18,292,293,294,330]. More recently, it has been proposed that low VB 12 levels, which can be associated with PPI treatment [297], affects skeletal fragility through the modulation of collagen cross-linking independently of areal bone mineral density [343]. This increased bone fragility coupled with recently evidence reporting an increased risk of falling in elderly patients with PPIs use may be contributing to increasing bone fracture rates [343,344,345,346].…”

Section: Insights Of Effects Of Chronic Hypergastrinemia In Patienmentioning

confidence: 99%

“…More recently, it has been proposed that low VB 12 levels, which can be associated with PPI treatment [297], affects skeletal fragility through the modulation of collagen cross-linking independently of areal bone mineral density [343]. This increased bone fragility coupled with recently evidence reporting an increased risk of falling in elderly patients with PPIs use may be contributing to increasing bone fracture rates [343,344,345,346]. Although a placebo controlled, double-blind trial in postmenopausal females found decreased calcium absorption with PPI treatment, the results suggesting PPI causes osteoporosis are largely negative [18,334,347,348], as are studies reporting PPI treatment does not cause changes in bone mineral density or bone structure that would predispose to fracture [348].…”

Section: Insights Of Effects Of Chronic Hypergastrinemia In Patienmentioning

confidence: 99%

Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger–Ellison Syndrome

Lee

Ramos-Álvarez

Ito

et al. 2019

IJMS

View full text Add to dashboard Cite

The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25–70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10–20 years). Zollinger–Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.

show abstract

Proton pump inhibitors and fracture: they impair bone quality and increase fall risk?

Cited by 10 publications

References 21 publications

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

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

Establishing the Association Between Osteoporosis and Peptic Ulcer Disease: A Systematic Review

Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger–Ellison Syndrome

Contact Info

Product

Resources

About