ArticleJournal of bone and mineral metabolism2016
Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors.
Article in Journal of bone and mineral metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid arthritis: a systematic review of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study.PloS one · 2017Trial
- [Methotrexate osteopathy-a critical review].Zeitschrift fur Rheumatologie · 2026Review
- Real-world identification of high-risk medications for drug-induced osteoporosis: a multi-method pharmacovigilance study based on FAERS with WHO Vigibase validation.Frontiers in endocrinology · 2026Article
- Nitazoxanide alleviates collagen-induced arthritis by inhibiting STAT3-dependent Th17 cell differentiation and inflammatory cytokines production.Frontiers in pharmacology · 2026Article
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis.European journal of rheumatology · 2025Article
- Supramolecular drug-laden hydrogel based on structural tautomerization enhances drug delivery for rheumatoid arthritis treatment.Bioactive materials · 2025Article
- Osteoporosis and Rheumatoid Arthritis: Mechanisms Underlying Osteoclast Differentiation and Activation or Factors Associated with Hip Fractures.Journal of clinical medicine · 2025Review
- Article
- MTX Osteopathy Versus Osteoporosis Including Response to Treatment Data-A Retrospective Single Center Study Including 172 Patients.Calcified tissue international · 2024Article
- Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans.EMBO molecular medicine · 2024Article
- Bezafibrate attenuates immobilization-induced muscle atrophy in mice.Scientific reports · 2024Article
- Overview of mechanisms and novel therapies on rheumatoid arthritis from a cellular perspective.Frontiers in immunology · 2024Review
- Luobitong Potentiates MTX's Anti-Rheumatoid Arthritis Activity via Targeting Multiple Inflammatory Pathways.Journal of inflammation research · 2024Article
- Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.International journal of molecular sciences · 2023Review
- The effect of disease-modifying antirheumatic drugs (DMARDs) on bone homeostasis in rheumatoid arthritis (RA) patients.Inflammopharmacology · 2023Review
- Methotrexate Increases Serum Calcium Levels in Patients with Rheumatoid Arthritis: A Retrospective Study at a Referral Hospital in Indonesia.Current therapeutic research, clinical and experimental · 2023Article
- Article
- Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increasing number of osteoporosis patients is a pressing issue worldwide. Osteoporosis frequently causes fragility fractures, limiting activities of daily life and increasing mortality. Many osteoporosis patients take numerous medicines due to other health issues; thus, it would be preferable if a single medicine could ameliorate osteoporosis and other conditions. Here, we screened 96 randomly selected drugs targeting various diseases for their ability to inhibit differentiation of osteoclasts, which play a pivotal role in development of osteoporosis, and identified methotrexate (MTX), as a potential inhibitor. MTX is currently used to treat sarcomas or leukemic malignancies or auto-inflammatory diseases such as rheumatoid arthritis (RA) through its anti-proliferative and immunosuppressive activities; however, a direct effect on osteoclast differentiation has not been shown. Here, we report that osteoclast formation and expression of osteoclastic genes such as NFATc1 and DC-STAMP, which are induced by the cytokine RANKL, are significantly inhibited by MTX. We found that RANKL-dependent calcium (Ca) influx into osteoclast progenitors was significantly inhibited by MTX. RA patients often develop osteoporosis, and osteoclasts are reportedly required for joint destruction; thus, MTX treatment could have a beneficial effect on RA patients exhibiting high osteoclast activity by preventing both osteoporosis and joint destruction.
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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.