I. Bergström, H. Isaksson, A. Koskela, J. Tuukkanen, C. Ohlsson, G. Andersson, S.H. Windahl, Prednisolone treatment reduces the osteogenic effects of loading in mice, Bone, Volume 112, 2018, Pages 10-18, ISSN 8756-3282, https://doi.org/10.1016/j.bone.2018.04.002
Prednisolone treatment reduces the osteogenic effects of loading in mice
|Author:||Bergström, I.1; Isaksson, H.2; Koskela, A.3;|
1Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, CLINTECH, Karolinska Institutet, Huddinge, Sweden
2Department of Biomedical Engineering, Lund University, Lund, Sweden
3Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland
4Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
5Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden
6Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, F46, Karolinska University Hospital, 141 86 Huddinge, Sweden
|Online Access:||PDF Full Text (PDF, 0.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019062822328
|Publish Date:|| 2019-06-28
Glucocorticoid treatment, a major cause of drug-induced osteoporosis and fractures, is widely used to treat inflammatory conditions and diseases. By contrast, mechanical loading increases bone mass and decreases fracture risk. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone. Three-month-old female C57BL/6 mice were treated with high-dose prednisolone (15 mg/60 day pellets/mouse) or vehicle for two weeks. During the treatment, right tibiae were subjected to short periods of cyclic compressive loading three times weekly, while left tibiae were used as physiologically loaded controls. The bones were analyzed using peripheral quantitative computed tomography, histomorphometry, real-time PCR, three-point bending and Fourier transform infrared micro-spectroscopy. Loading alone increased trabecular volumetric bone mineral density (vBMD), cortical thickness, cortical area, osteoblast-associated gene expression, osteocyte- and osteoclast number, and bone strength. Prednisolone alone decreased cortical area and thickness and osteoblast-associated gene expression. Importantly, prednisolone treatment decreased the load-induced increase in trabecular vBMD by 57% (p < 0.001) and expression of osteoblast-associated genes, while completely abolishing the load-induced increase in cortical area, cortical thickness, number of osteocytes and osteoclasts, and bone strength. When combined, loading and prednisolone decreased the collagen content. In conclusion, high-dose prednisolone treatment strongly inhibits the loading-induced increase in trabecular BMD, and abolishes the loading-induced increase in cortical bone mass. This phenomenon could be due to prednisolone inhibition of osteoblast differentiation and function.
|Pages:||10 - 18|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This study was supported by the Swedish Research Council (K2015-99X-10363-23-4 and 2013-2852), the ALF/LUA research grant in Gothenburg (161891) and Stockholm (2011-0347 and 2015-0466) and the Engineering and Physical Sciences Research Council (EP/H002693/1). We gratefully acknowledge beamtime at the D7 beamline at MAX III, MAX IV Laboratory, Lund, Sweden. The funding sources were not involved in in the study design, the collection, analysis or interpretation of data, the writing of the report, or the decision to submit this article for publication.
© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).