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Osteologie 2016; 25(04): 241-246
DOI: 10.1055/s-0037-1619026
Glukokortikoide und Knochen
Schattauer GmbH

Kortisolwirkungen im Knochen

Actions of glucocorticoids on bone
U. Baschant
1   Bereich Endokrinologie, Diabetes und Knochenerkrankungen, Medizinische Klinik III, Universitätsklinikum Dresden, Dresden
2   Zentrum für Gesundes Altern, Medizinische Fakultät der Technischen Universität Dresden, Dresden
,
M. Rauner
1   Bereich Endokrinologie, Diabetes und Knochenerkrankungen, Medizinische Klinik III, Universitätsklinikum Dresden, Dresden
2   Zentrum für Gesundes Altern, Medizinische Fakultät der Technischen Universität Dresden, Dresden
,
E. Tsourdi
1   Bereich Endokrinologie, Diabetes und Knochenerkrankungen, Medizinische Klinik III, Universitätsklinikum Dresden, Dresden
2   Zentrum für Gesundes Altern, Medizinische Fakultät der Technischen Universität Dresden, Dresden
,
L. C. Hofbauer
1   Bereich Endokrinologie, Diabetes und Knochenerkrankungen, Medizinische Klinik III, Universitätsklinikum Dresden, Dresden
2   Zentrum für Gesundes Altern, Medizinische Fakultät der Technischen Universität Dresden, Dresden
3   DFGCenter for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden
› 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

Eine Glukokortikoid-induzierte Osteoporose ist eine schwere Komplikation einer Langzeit- Glukokortikoidtherapie und die häufigste Form der sekundären Osteoporosen. Die zugrundeliegenden Mechanismen der Pathogenese sind komplex. Glukokortikoide haben vielfältige physiologische Funktionen, wie die Regulation des Glukosestoffwechsels. Obwohl Glukokortikoide in physiologischen Konzentrationen für die Knochenentwicklung notwendig sind, wirken sie in therapeutischen Konzentrationen katabol auf den Knochen. Sie begünstigen die Aktivität der knochen resorbierenden Osteoklasten und hemmen gleichzeitig langfristig die knochenbildenden Osteoblasten und Osteozyten. Die frühzeitige Anwendung von Bisphosphonaten reduziert effektiv das Auftreten von Frakturen und die Therapie mit Teriparatid verhindert die Hemmung der Knochenformation, verbessert die Knochenqualität und führt zur einer signifikanten Frakturreduktion bei Patienten mit Glukokortikoid-induzierter Osteoporose. Weitere osteoanabol wirkende Substanzen, wie Romosozumab, ein monoklonaler Antikörper gegen Sklerostin, befinden sich in der klinischen Erprobung und könnten attractive Therapiealternativen für die Behandlung der Glukokortikoid-induzierten Osteoporose darstellen.

Summary

Glucocorticoid-induced osteoporosis is a severe side effect of long-term glucocorticoid therapy and the most common form of secondary osteoporosis. The molecular mechanisms underlying the deleterious effects of glucocorticoids in bone are complex. Glucocorticoids exert several physiological metabolic actions including the regulation of glucose homeostasis and lipid metabolism and play a pivotal role in the regulation of inflammatory processes as well as in the maintenance of circadian rhythms and regulation of acute and chronic stress. They have multiple effects on fetal development and in physiological concentrations, they are necessary for bone accrual and growth. Nevertheless, supraphysiological concentrations of glucocorticoids, either as part of the treatment of chronic inflammatory medical conditions or as a result of Cushing’s syndrome negatively affect the bone. They enhance the activity of the boneresorbing osteoclasts through the up-regulation of M-CSF und RANKL and concomitant down-regulation of OPG and activate inhibitors of the Wnt-signaling pathway such as sclerostin, thereby thwarting bone formation. Their direct inhibitory actions on bone-forming osteoblasts and osteocytes are considered pivotal for the pathogenesis of glucocorticoid-induced osteoporosis. Supraphysiological glucocorticoid concentrations block osteoblast differentiation and proliferation, activate pro-apoptotic signaling pathways in osteoblasts and osteocytes and hamper the mineralization process. Currently, therapeutic options to treat patients with glucocorticoid-induced osteoporosis are anti-resorptive and osteoanabolic drugs. The rationale of an early-on treatment with antiresorptive drugs is based on the fact that glucocorticoids lead to an initial phase of accentuated bone resorption. Thus, clinical studies have proven that bisphosphonates are effective at reducing the occurrence of fractures in patients with glucocorticoid-induced osteoporosis. On the other hand, the inhibitory actions of glucocorticoids on bone formation render osteoanabolic drugs very attractive therapeutic options. The intermittent therapy with teriparatide leads to a significant improvement of bone architecture and strength parameters as well as to a reduction of vertebral fractures and should thus be implemented especially by patients with severe forms of glucocorticoid-induced osteoporosis. Novel osteoanabolic agents such as romosozumab, a monoclonal antibody against sclerostin are currently being evaluated in clinical studies.

Schlüsselwörter

Glukokortikoid-induzierte Osteoporose - Frakturrisiko - Knochenstoffwechsel

Keywords

Glucocorticoid-induced osteoporosis - fracture risk - bone homeostasis
 

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