ArticleThe Journal of clinical investigation2000
Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 2 of them syntheses 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
291 citing papers in PubMed, 2 syntheses or guidelines pooled it, 687 citations in OpenAlex.
- The role of CD8Frontiers in immunology · 2026Pooled it
- Exercise for improving bone health in women treated for stages I-III breast cancer: a systematic review and meta-analyses.Journal of cancer survivorship : research and practice · 2017Pooled it
- Low baseline CD4+ count is associated with greater bone mineral density loss after antiretroviral therapy initiation.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2013Trial
- C-type lectin receptors: bone remodeling and therapeutic potential.Bone research · 2026Review
- Sigma Anti-bonding Calcium Attenuates Ovariectomy-Induced Bone Loss by Preserving Trabecular Microarchitecture and Suppressing Osteoclastogenesis.Calcified tissue international · 2026Article
- Independent Associations of Appendicular Skeletal Muscle Mass Index and Waist Circumference with Site-Specific Bone Mineral Density in Postmenopausal Women: A Real-World Cross-Sectional Study.Healthcare (Basel, Switzerland) · 2026Article
- CSF1R+ macrophage and osteoclast depletion impairs neural crest proliferation and craniofacial morphogenesis.Development (Cambridge, England) · 2026Article
- Article
- Changes in Oxidative Stress, Inflammatory and Bone Metabolism Biomarkers Following Sulfurous Water Inhalation in Osteopenic Women.International journal of molecular sciences · 2026Article
- Osteoimmune senescence in aging bone: from inflammaging dogma to cell-type-specific therapeutic windows.Frontiers in immunology · 2026Review
- Osteoimmunology: interactions of the bone and immune system.Frontiers in immunology · 2026Review
- The estrogen-ferroptosis axis in postmenopausal osteoporosis, osteoarthritis, and intervertebral disc degeneration: shared mechanisms and emerging evidence.Frontiers in immunology · 2026Review
- Inflammaging and immunosenescence-driven remodeling of the immune microenvironment in osteoarthritis: mechanisms, immune regulation and immune reprogramming.Frontiers in immunology · 2026Review
- RANKL-convergent osteoimmune network framework in osteoporosis: integrating macrophage activation, T-cell imbalance, and cytokine crosstalk.Frontiers in immunology · 2026Review
- Osteoporosis and Fracture Risk in Ovarian Cancer: Beyond the Oncologic Burden.Diagnostics (Basel, Switzerland) · 2025Review
- Up-regulation of Ifi27l2a expression in bone marrow monocytes contributes to glucocorticoid-induced bone loss.Communications biology · 2025Article
- Adipose Tissue Macrophages as Initiators of Exacerbated Periodontitis in Estrogen-Deficient Environments via the Amplifier Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The impact of alpha-lipoic acid treatment on various mediators of inflammatory and immune responses in a murine arthritis model.Inflammopharmacology · 2025Article
- Bone marrow neutrophil progenitors suppress osteoclast formation in murine cortical and trabecular bone.Blood · 2025Article
- Genome-Wide Association Study of Osteoporosis Risk in Korean Pre-Menopausal Women: The Korean Genome and Epidemiology Study.International journal of molecular sciences · 2025Article
231 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Estrogen deficiency induces bone loss by upregulating osteoclastogenesis by mechanisms not completely defined. We found that ovariectomy-enhanced T-cell production of TNF-alpha, which, acting through the TNF-alpha receptor p55, augments macrophage colony-stimulating factor-induced (M-CSF-induced) and RANKL-induced osteoclastogenesis. Ovariectomy failed to induce bone loss, stimulate bone resorption, or increase M-CSF- and RANKL-dependent osteoclastogenesis in T-cell deficient mice, establishing T cells as essential mediators of the bone-wasting effects of estrogen deficiency in vivo. These findings demonstrate that the ability of estrogen to target T cells, suppressing their production of TNF-alpha, is a key mechanism by which estrogen prevents osteoclastic bone resorption and bone loss.
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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.