ArticleThe Journal of clinical investigation2003
A crucial role for thiol antioxidants in estrogen-deficiency bone loss.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 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
204 citing papers in PubMed, 2 syntheses or guidelines pooled it, 477 citations in OpenAlex.
- Correlation of oxidative stress-related biomarkers with postmenopausal osteoporosis: a systematic review and meta-analysis.Archives of osteoporosis · 2021Pooled it
- Effects of Caffeic Acid and Its Derivatives on Bone: A Systematic Review.Drug design, development and therapy · 2021Pooled it
- Association of Menopause and Hormone Replacement Therapy with Hearing Loss.The Annals of otology, rhinology, and laryngology · 2026Article
- METTL5 deficiency impairs osteogenesis through OSER1-dependent antioxidant regulation.JCI insight · 2026Article
- Article
- The estrogen-ferroptosis axis in postmenopausal osteoporosis, osteoarthritis, and intervertebral disc degeneration: shared mechanisms and emerging evidence.Frontiers in immunology · 2026Review
- Ferroptosis in compromised bone healing after trauma: from the iron/ROS microenvironment to non-union and bone defect reconstruction.Frontiers in medicine · 2026Review
- Comparison of calcium hydroxide removal efficiency of ethylenediaminetetraacetic acid, phytic acid and N-acetylcysteine using sonic activation: a micro-CT study.BMC oral health · 2025Article
- Update on the correlation between mitochondrial function and osteonecrosis of the femoral head osteocytes.Redox report : communications in free radical research · 2025Review
- Nrf2 signaling in bone health: unlocking new avenues for osteoporosis management.Inflammopharmacology · 2025Review
- Sex-dependent variation in bone adaptation: from degeneration to regeneration.Journal of orthopaedic translation · 2025Review
- Chk2 deletion rescues bone loss and cellular senescence induced by Bmi1 deficiency via regulation of Cyp1a1.Journal of orthopaedic translation · 2025Article
- Ashwagandha and Shatavari Extracts Dose-Dependently Reduce Menopause Symptoms, Vascular Dysfunction, and Bone Resorption in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Study.Journal of menopausal medicine · 2025Article
- Enhanced antibiotic release and biocompatibility with simultaneous addition of N-acetylcysteine and vancomycin to bone cement: a potential replacement for high-dose antibiotic-loaded bone cement.Journal of orthopaedic surgery and research · 2025Article
- Divergent Requirements for Glutathione Biosynthesis During Osteoclast Differentiation In Vitro and In Vivo.Antioxidants (Basel, Switzerland) · 2025Article
- Nrf2 Activation as a Therapeutic Target for Flavonoids in Aging-Related Osteoporosis.Nutrients · 2025Review
- Age-stratified association between serum uric acid and lumbar bone mineral density in elderly Chinese women with vertebral compression fractures: a cross-sectional analysis.Frontiers in medicine · 2025Article
- Imbalance of Bone Homeostasis Caused by Nrf2 Deficiency Leads to Bone Loss in OVX Rats.Stem cells international · 2025Article
- Anthocyanins and musculoskeletal diseases: mechanisms and therapeutic potential.Frontiers in nutrition · 2025Review
- Improvement of antioxidant capability by dietary N-acetyl cysteine supplementation alleviates bone loss induced by chronic heat stress in finisher broilers.Journal of animal science and biotechnology · 2024Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanisms through which estrogen prevents bone loss are uncertain. Elsewhere, estrogen exerts beneficial actions by suppression of reactive oxygen species (ROS). ROS stimulate osteoclasts, the cells that resorb bone. Thus, estrogen might prevent bone loss by enhancing oxidant defenses in bone. We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-beta estradiol. Moreover, administration of N-acetyl cysteine (NAC) or ascorbate, antioxidants that increase tissue glutathione levels, abolished ovariectomy-induced bone loss, while l-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis, caused substantial bone loss. The 17-beta estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro. Furthermore, in vitro NAC prevented osteoclast formation and NF-kappaB activation. BSO and hydrogen peroxide did the opposite. Expression of TNF-alpha, a target for NF-kappaB and a cytokine strongly implicated in estrogen-deficiency bone loss, was suppressed in osteoclasts by 17-beta estradiol and NAC. These observations strongly suggest that estrogen deficiency causes bone loss by lowering thiol antioxidants in osteoclasts. This directly sensitizes osteoclasts to osteoclastogenic signals and entrains ROS-enhanced expression of cytokines that promote osteoclastic bone resorption.
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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.