Multiscale assessment of glucocorticoid-induced alterations across bone marrow and mineralized bone in human iliac crest biopsies

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ID: 329599
2026
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Ranked #126 of 133 articles by views in journal of bone and mineral research : the official journal of the american society for bone and mineral research

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Abstract
BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is associated with a fracture risk that exceeds what would be expected based on bone mineral density (BMD) alone, suggesting impaired bone quality. In contemporary clinical practice, patients receiving glucocorticoids are typically treated concomitantly with anti-osteoporotic medication, limiting the ability to define glucocorticoid-specific effects on human bone tissue. METHODS: We performed a retrospective case-control study of archived iliac crest biopsies from patients with established GIOP (n=21) who had received glucocorticoid therapy without concomitant anti-osteoporotic treatment, identified through a dedicated bone biopsy registry. Age-matched non-GIOP controls (n=13) were included for comparison. A comprehensive multiscale approach combining micro-computed tomography, static histomorphometry, quantitative mineral analysis, Raman spectroscopy, and nanoindentation was used to assess trabecular microarchitecture, cellular remodeling, matrix composition, and tissue-level mechanical properties. RESULTS: Glucocorticoid exposure was associated with significantly reduced trabecular bone volume fraction driven by trabecular thinning. Bone formation was suppressed, as reflected by decreased osteoblast surface and osteoid thickness, while erosion depth was increased. Viable osteocyte density was reduced and marrow adiposity elevated. At the material level, bone exhibited increased mean calcium content and greater mineral homogeneity, accompanied by reduced pyridinoline and glycosaminoglycan content and diminished mineral crystallinity. These compositional alterations were associated with a significantly lower elastic modulus. CONCLUSION: Analysis of this unique registry-based biopsy collection demonstrates coordinated alterations in bone remodeling cells, trabecular architecture, mineral distribution, collagen matrix composition, and mechanical competence in glucocorticoid-treated bone. To our knowledge, this integrated cellular-to-material characterization has not previously been performed in human biopsies exposed exclusively to glucocorticoids and provides mechanistic insight into the pathophysiology underlying glucocorticoid-associated skeletal fragility.
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openalex_W7214125375 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Praveer Sihota, Xenia Junimann, Johannes Krug, Jan Frischmuth, Lukas Harms, Timur Alexander Yorgan, Imke A K Fiedler, Annegreet Vlug, Björn Jobke, Michael Amling, Mathias Werner, Katharina Jähn, Björn Busse
Journal journal of bone and mineral research : the official journal of the american society for bone and mineral research
Year 2026
DOI
10.1093/jbmr/zjag140
URL
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