ArticleJournal of clinical biochemistry and nutrition2012
Bisphosphonate-induced gastrointestinal mucosal injury is mediated by mitochondrial superoxide production and lipid peroxidation.
Article in Journal of clinical biochemistry and nutrition, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Safety of drug use in patients with a primary mitochondrial disease: An international Delphi-based consensus.Journal of inherited metabolic disease · 2020Guideline
- Oral Treatment With Bisphosphonates of Osteoporosis Does Not Increase the Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials.Frontiers in endocrinology · 2020Pooled it
- Article
- Perforation of gastric volvulus within a giant hiatus hernia secondary to alendronate: A rare complication of bisphosphonate use.International journal of surgery case reports · 2020Article
- Pharmacology of bisphosphonates.British journal of clinical pharmacology · 2019Review
- The preventive effect of Qing Dai on bisphosphonate-induced gastric cellular injuries.Journal of clinical biochemistry and nutrition · 2019Article
- A case-control study of the risk of upper gastrointestinal mucosal injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from the Japanese national claims database of 13 million accumulated patients.Journal of gastroenterology · 2018Article
- Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress.Drug design, development and therapy · 2016Article
- Osteonecrosis of the jaw in a Crohn's disease patient following a course of Bisphosphonate and Adalimumab therapy: a case report.BMC gastroenterology · 2014Article
- Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion.Journal of clinical biochemistry and nutrition · 2014Article
- Alendronate sodium hydrate (oral jelly) for the treatment of osteoporosis: review of a novel, easy to swallow formulation.Clinical interventions in aging · 2013Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bisphosphonates such as alendronate and risedronate are commonly used for the treatment of postmenopausal osteoporosis. They have the gastrointestinal adverse effects such as erosions and ulcers in stomach and small intestine. However, the detailed biological mechanism remains to be elucidated. Since alendronate is suggested to increase the risk of non-steroidal anti-inflammatory drug-related gastropathy, we hypothesized that bisphosphonates and non-steroidal anti-inflammatory drugs have the same pathophysiological mechanisms in gastrointestinal mucosa: Bisphosphonates may induce cellular lipid peroxidation by inducing the production of mitochondrial superoxide. We also hypothesized that geranylgeranylacetone, an antiulcer drug, may prevent lipid peroxidation by reducing superoxide production. We treated gastric RGM1 cells and small intestinal IEC6 cells with alendronate or risedronate, and examined cellular injury, lipid peroxidation and superoxide production with specific fluorescent dyes, and underwent electron paramagnetic resonance spectroscopy to detect the production of superoxide in vitro. The results indicated that bisphosphonates indeed induced cellular injury, cellular lipid peroxidation, and superoxide production. We also demonstrated that the pretreatment of geranylgeranylacetone decreased superoxide production and prevented cellular lipid peroxidation. These results suggested that bisphosphonates, like non-steroidal anti-inflammatory drugs, induce lipid peroxidation by producing mitochondrial superoxide, which was prevented by geranylgeranylacetone.
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Registered trials
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