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Osteologie 2016; 25(04): 247-252
DOI: 10.1055/s-0037-1619025
Glukokortikoide und Knochen
Schattauer GmbH

Zelluläre Mechanismen der Gluko-kortikoid-induzierten Osteoporose und therapeutische Ansatzpunkte

Zelluläre Mechanismen und neuartige therapeutische AnsätzeGlucocorticoids and the skeletonCellular mechanisms and novel therapeutic approaches
H. Henneicke
1   Medizinische Klinik III, Zentrum für Gesundes Altern & DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Deutschland
,
S.J. Gasparini
2   Bone Biology Program, ANZAC Research Institute, The University of Sydney at Concord, Sydney, Australia
,
H. Zhou
2   Bone Biology Program, ANZAC Research Institute, The University of Sydney at Concord, Sydney, Australia
,
L.C. Hofbauer
1   Medizinische Klinik III, Zentrum für Gesundes Altern & DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Deutschland
,
M.J. Seibel
3   Bone Biology Program, ANZAC Research Institute, Department of Endocrinology and Metabolism, The University of Sydney at Concord, Sydney, Australia
› Author Affiliations
Further Information

Publication History

eingereicht: 13 September 2016

angenommen: 27 September 2016

Publication Date:
23 December 2017 (online)

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Zusammenfassung

Der therapeutische Einsatz von Glukokortikoi-den ist aufgrund ihrer potenten immunmodu-latorischen Wirkung häufig unverzichtbar. Je-doch ist der klinische Nutzen aufgrund ihres Nebenwirkungsprofils oft begrenzt. Im Skelett-system führt eine länger dauernde systemische Therapie mit Glukokortikoiden zu einem rapi-den Verlust von Knochenmasse sowie einer deutlichen Steigerung des Frakturrisikosins-besondere an der Wirbelsäule. Im Verlauf der vergangenen Jahre hat sich das Verständnis der skelettalen Effekte von Glukokortikoiden durch den Einsatz genetisch modifizierter Mäu-se deutlich verbessert: Glukokortikoide intera-gieren mit allen Zellen im Knochen, jedoch werden die skelettalen Nebenwirkungen einer Glukokortikoidtherapie primär durch eine verminderte Osteoblasten- und Osteozytenfunkti-on verursacht. Aufgrund dieses Wirkmechanismus legen präklinische Studien in Modellorga-nismen als auch Studien bei Patienten mit Glu-kokortikoid-induzierter Osteoporose den Schluss nahe, dass eine osteoanabole Therapie einer Therapie mit Antiresorptiva langfristig überlegen sein kann. In diesem Artikel fassen wir neue Er-kenntnisse über die Glukokortikoidwirkung im Knochen systematisch zusammen und diskutie-ren deren Konsequenzen für die Therapie der Glukokortikoid-induzierten Osteoporose.

Summary

Although glucocorticoids are highly effective in the treatment of autoimmune inflammatory diseases, their use is limited by significant adverse outcomes including diabetes, sarcopenia and osteoporosis. Recent insights into the skeletal mechanisms of glucocorticoid action have identified osteoblasts and osteocytes as their main target cells in bone. At supraphysiological levels, glucocorticoids suppress osteoblastogenesis and osteoblast function, induce osteoblast cell cycle arrest and apoptosis and redirect mesenchymal stem cell differentiation towards the adipocyte lineage. More recently, disturbances in the lacunar-canalicular system and reduced osteocyte viability have been identified to also negatively affect skeletal health during glucocorticoid therapy. As the predominant active mechanism in glucocorticoid-induced osteoporosis is the suppression of bone formation, concerns have been raised about the long-term use of anti-resorptive agents in these patients. Thus, osteo-anabolic treatments such as Teriparatide, which stimulate osteoblast activity and bone modelling, may be better suited to address the pathomechanism underlying glucocorticoid-induced osteoporosis. In regards to the metabolic adverse effects of glucocorti-coids (i. e. insulin resistance, diabetes), recent studies in rodents have indicated that the bone-derived peptide, osteocalcin, may play a role in mediating some of these outcomes. These findings link the detrimental effects of glucocorticoids on energy metabolism directly to their suppressive actions on bone cells. In this article, we review the pathophysiology of glucocorticoid action on bone cells, and discuss current and novel concepts regarding the cellular mechanisms underlying adverse effects of glucocorticoids such as osteoporosis and diabetes.

Schlüsselwörter

Glukokortikoide - Osteoporose - Osteoblast - Osteoklast - Osteokalzin - 11 β-Hydroxysteroid-dehydrogenase Typ 2 (11β-HSD2)

Keywords

Glucocorticoids - osteoporosis - osteoblast - osteoclast - osteocalcin - 11 β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2)
 

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