Der Einfluss von Schilddrüsenhormonen auf den Knochen – von der zellulären Ebene, über Mausmodelle bis hin zum Patienten

Zusammenfassung

Die Schilddrüsenhormone L-Thyroxin und 3,3',5-Triiod-L-thyronin spielen eine zentrale Rolle im Skelettwachstum und beim Erhalt eines gesunden Knochens im Erwachsenenalter. Auf zellulärer Ebene sind die Wirkungen von Schilddrüsenhormonen in Osteoblasten gut erforscht, während ihre Effekte auf Osteoklasten und Osteozyten nur unzureichend verstanden sind. Die Behandlung von Osteoblasten mit Schilddrüsenhormonen in vitro führt zu deren Leistungssteigerung, wobei drei wesentliche Faktoren ihre zelluläre Wirksamkeit bestimmen können: der Import in die Zelle, ihre Aktivierung oder Inaktivierung durch Dejodasen und die Verfügbarkeit der Schilddrüsenhormonrezeptoren. Präklinische Studien unter Verwendung transgener Mausmodelle zeigen, dass jeder dieser Faktoren eine wesentliche Rolle im Skelettwachstum und dem Erhalt der Knochenqualität, -struktur und -mineraldichte spielen. Schilddrüsenerkrankungen führen zu unterschiedlichen skelettalen Veränderungen im Kindes- und Erwachsenenalter und können in der Regel durch eine Therapie gut behandelt werden. Sowohl eine Hypo- als auch Hyperthyreose kann, wenn unbehandelt, im Kindesalter zu Kleinwuchs führen. In erwachsenen Betroffenen verursacht eine manifeste Hyperthyreose eine sekundäre Osteoporose mit erhöhten Frakturrisiko infolge eines gesteigerten Knochenaufbaus und -abbaus. Eine Hypothyreose hingegen verlangsamt den Knochenumbauzyklus und steigert die sekundäre Mineralisierung. Da Schilddrüsenhormone den Knochenumbau direkt regulieren können, nehmen sie ebenfalls Einfluss auf die Kalzium- und Phosphathomöostase im Körper. Zusammengefasst sind Schilddrüsenhormone wichtige Regulatoren des Knochen- und Mineralstoffwechsels.

Abstract

The thyroid hormones L-thyroxine und 3,3',5-triiodo-L-thyronine are critical regulators of skeletal development and maintenance of a healthy bone in adults. While direct actions of thyroid hormones on osteoblasts are well established, only little is known about thyroid hormone signaling in osteoclasts and especially osteocytes. Thyroid hormones increase osteoblast differentiation and function in vitro. Three main factors determine their biological activity: their import via specific transporter proteins, their activation or inactivation mediated by deiodinases and the thyroid hormone receptor availability. Preclinical studies using transgenic mouse models demonstrated that every one of these factors determines bone quality, structure and mineral density. Thyroid disorders can cause distinct skeletal changes during childhood and adulthood that usually can be medically treated. During childhood, untreated hypothyroidism and hyperthyroidism both can cause short stature. In adults, hyperthyroidism is a known cause of secondary osteoporosis with an increased fracture risk due to enhanced bone formation and especially bone resorption. In contrast, hypothyroid patients display a prolonged bone remodeling cycle and increased secondary mineralization. Given that thyroid hormones directly affect bone turnover, they can also regulate the whole-body calcium and phosphate homeostasis. Thus, thyroid hormones play an important role in bone and mineral metabolism.

Schlüsselwörter

Hyperthyreose - Hypothyreose - Schilddrüsenhormontransporter - Schilddrüsenhormonrezeptor - Osteoporose

Key words

Hyperthyroidism - hypothyroidism - thyroid hormone transporter - thyroid hormone receptor - osteoporosis

Publikationsverlauf

Eingereicht: 26. Juli 2022

Angenommen nach Revision: 23. September 2022

Artikel online veröffentlicht:
14. Dezember 2022

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