ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2011
Mechanisms inducing low bone density in Duchenne muscular dystrophy in mice and humans.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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75 citing papers in PubMed, 145 citations in OpenAlex.
- Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug.Pharmacological research · 2018Trial
- Anti-Receptor Activator of Nuclear Factor-κB Ligand Improves Muscle Dysfunction and Strengthens Bone in Laminin-α2-Deficient dyThe American journal of pathology · 2026Article
- Voluntary running sustains the correction of inflammation-related gene expression conferred by AAV gene therapy in mdx mice.Molecular therapy. Advances · 2026Article
- Pyroxd1 is essential for murine viability with the homozygous N155S recurrent variant linked to myopathy, muscle hypotrophy and osteopenia.Acta neuropathologica communications · 2026Article
- Tauroursodeoxycholic acid-induced increase in ectopic muscle mineralization occurs exclusively in dystrophic muscles and is independent of endoplasmic reticulum stress.Scientific reports · 2025Article
- Is dystrophin immunogenicity a barrier to advancing gene therapy for Duchenne muscular dystrophy?Gene therapy · 2025Review
- Obligatory and accessory respiratory muscle structure, function and control in early and advanced disease in the mdx mouse model of Duchenne muscular dystrophy.The Journal of physiology · 2025Article
- Neuronal hyperexcitability in dystrophin-deficient mdx hippocampal neurons: the importance of interleukin-6 and GABAergic regulation.Scientific reports · 2025Article
- Fractures in Hereditary Neuromuscular Disorders: Frequency, Risk Factors, and Implications.European journal of neurology · 2025Article
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Circulatory CCL2 distinguishes Duchenne muscular dystrophy dogs.Disease models & mechanisms · 2025Article
- Review
- Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology.Calcified tissue international · 2024Article
- The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy.Disease models & mechanisms · 2024Article
- How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?Proteomes · 2024Article
- Poor bone health in Duchenne muscular dystrophy: a multifactorial problem beyond corticosteroids and loss of ambulation.Frontiers in endocrinology · 2024Review
- Investigating mechanical and inflammatory pathological mechanisms in osteoarthritis using MSC-derived osteocyte-like cells in 3D.Frontiers in endocrinology · 2024Article
- Amyotrophic lateral sclerosis and osteoporosis: a two-sample Mendelian randomization study.Frontiers in aging neuroscience · 2023Article
- Serum inflammatory cytokines as disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy.Disease models & mechanisms · 2022Article
- Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.JCI insight · 2022Article
15 more citing papers are in PubMed but not listed here.
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14 authors at 6 institutions in 2 countries.
Funding
Abstract
Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro-computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-βA, and TGFβ2 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients.
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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.