ArticleCalcified tissue international2021
Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro.
Article in Calcified tissue international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- The Effect of Proton Pump Inhibitors on Bone MineralisationSultan Qaboos University medical journal · 2025Pooled it
- Lansoprazole Increases Inorganic Pyrophosphate in Patients with Pseudoxanthoma Elasticum: A Double-Blind, Randomized, Placebo-Controlled Crossover Trial.International journal of molecular sciences · 2023Trial
- Impact of Proton Pump Inhibitor Therapy on Bone Mineral Density: An Updated Systematic Review.Cureus · 2026Review
- Drug-Induced Osteoporosis.Journal of clinical medicine · 2026Review
- Differential fracture risk among proton pump inhibitors in older adults: evidence network and pharmacovigilance validation.Frontiers in pharmacology · 2026Article
- Hidden targets in dermatology:Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Review
- Osteoblasts sense extracellular levels of phosphate to control the local expression of phosphatases for matrix mineralisation.Bone reports · 2025Article
- Bone marrow adipose tissue expansion and bone loss in experimental chronic kidney disease is independent of altered bone marrow stromal cell lineage determination.Frontiers in endocrinology · 2025Article
- Article
- Repurposing lansoprazole to alleviate metabolic syndromeActa pharmaceutica Sinica. B · 2024Article
- The mechanism of biomineralization: Progress in mineralization from intracellular generation to extracellular deposition.The Japanese dental science review · 2023Review
- Proton Pump Inhibitors and Bone Health: An Update Narrative Review.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear, but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPIs tested inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73 µM for esomeprazole to 19.27 µM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures was inhibited by several PPIs in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments show for the first time that PPIs inhibit PHOSPHO1 activity and matrix mineralisation in vitro revealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.