ArticleArthritis research & therapy2019
11β-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy.
Article in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 3 of them syntheses that pooled it.
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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.
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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
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Meta-analysis of the efficacy and safety of vamorolone in Duchenne muscular dystrophy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis.Frontiers in neurology · 2023Pooled it
- Animal Model for Glucocorticoid Induced Osteoporosis: A Systematic Review from 2011 to 2021.International journal of molecular sciences · 2021Pooled it
- Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial.Neurology · 2026Trial
- Adrenal Suppression From Vamorolone and Prednisone in Duchenne Muscular Dystrophy: Results From the Phase 2b Clinical Trial.The Journal of clinical endocrinology and metabolism · 2025Trial
- Efficacy and Safety of Vamorolone Over 48 Weeks in Boys With Duchenne Muscular Dystrophy: A Randomized Controlled Trial.Neurology · 2024Trial
- 11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial.Nature communications · 2023Trial
- 11βHSD1 Inhibition with AZD4017 Improves Lipid Profiles and Lean Muscle Mass in Idiopathic Intracranial Hypertension.The Journal of clinical endocrinology and metabolism · 2021Trial
- Defining the potential role of the mineralocorticoid receptor in musculoskeletal health and bone crosstalk with other tissues.The Journal of endocrinology · 2026Review
- Small-Molecule Strategies for Polymyalgia Rheumatica and Giant Cell Arteritis in Older Adults.Molecules (Basel, Switzerland) · 2026Review
- Article
- Chronic Stress Leads to Time-Dependent Bone Loss Through HPA Axis Dysregulation and GR Nuclear Translocation Disorder.International journal of molecular sciences · 2026Article
- A Novel Murine Model to Study the Early Biological Events of Corticosteroid-Associated Osteonecrosis of the Femoral Head.Bioengineering (Basel, Switzerland) · 2026Article
- Post-marketing safety surveillance and signal characterization of the novel dissociative steroid Vamorolone in Duchenne muscular dystrophy: a comparative disproportionality analysis based on FAERS data.Frontiers in pharmacology · 2026Article
- Therapeutic Management of Glucocorticoid-Induced Osteoporosis with a Focus on Older Adults: A Narrative Review.Drugs & aging · 2026Review
- Context-dependent roles of 11β-HSD1 in bone and skeletal muscle diseases.American journal of translational research · 2026Review
- Vamorolone: a novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effects.Rheumatology (Oxford, England) · 2025Article
- Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space.Advanced healthcare materials · 2025Article
- Tau(t)ing glucocorticoid binding.Cell research · 2025Article
- Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity.Nature communications · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundDespite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP.
methodsWild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR.
resultsWild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone.
conclusionsThis study demonstrates that 11β-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids.
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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.