Session Information
Date: Monday, November 18, 2024
Title: Osteoporosis & Metabolic Bone Disease – Basic & Clinical Science Poster
Session Type: Poster Session C
Session Time: 10:30AM-12:30PM
Background/Purpose: Osteoporosis is a bone disease characterized by low bone mass and changes in bone architecture, often leading to pain, fractures and reduced mobility in affected patients. Glucocorticoid-induced osteoporosis (GIOP) is known as the most important form of secondary osteoporosis. To set up a GIOP in vitro model, we established and characterized a human in vitro bone model, subsequently using methylprednisolone to induce GIOP and later treat the model with anti-osteoporotic drugs.
Methods: To provide the basic scaffold for the structure of the bone model, mesenchymal stromal cells (MSCs)
were differentiated on β-TCP. Afterwards, human osteoclasts, differentiated from CD14+ monocytes, were added, and the models were treated with 10-6 M methylprednisolone to induce osteoporosis. As pharmacological treatment of GIOP, we used alendronic acid and denosumab. Bone forming and resorbing activity was monitored using μ-computed tomography (µ-CT), supernatant analysis, gene expression, scanning electron microscopy and immunofluorescence.
Results: Results showed that a ratio of 104 osteoblasts and 5*103 osteoclasts works best. We furthermore analysed the supernatant and detected secretion of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), osteoprotegerine (OPG), matrixmetallopeptidase 9 (MMP-9), free phosphate, and calcium. Our results confirmed the functionality of our 3D model. Subsequently, we transferred our untreated model to the osteoporosis-simulating model by treating with methylprednisolone and could show a disruption of bone homeostasis in favour of osteoclast activity. If these models were treated with alendronic acid or denosumab, markers of bone metabolism (Ca2+, ALP, bone volume) returned to pre-pathophysiological.
Conclusion: Ultimately, we obtained an in vitro 3D co-culture of osteoblasts and osteoclasts simulating human native bone capable of mimicking key aspects of GIOP in vitro via treatment with methylprednisolone. As a proof of concept, GIOP was treated with established antiresorptive drugs showing an increase of osteogenesis markers.
To cite this abstract in AMA style:
Plank J, Pfeiffenberger M, Damerau A, Gaber T, DR. BUTTGEREIT F. Generation of a Human 3D Bone Model to Mimic Glucocorticoid- induced Osteoporosis In Vitro [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/generation-of-a-human-3d-bone-model-to-mimic-glucocorticoid-induced-osteoporosis-in-vitro/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/generation-of-a-human-3d-bone-model-to-mimic-glucocorticoid-induced-osteoporosis-in-vitro/