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Osteologie 2019; 28(01): 21-27
DOI: 10.1055/a-0807-7710
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Teriparatid – Das molekulare und klinische Profil bei der Therapie der Osteoporose

Teriparatide – The molecular and clinical profile in osteoporosis treatment
Franz Jakob
Bernhard-Heine-Centrum für Bewegungsforschung, Klinische und Experimentelle Osteologie, Universität Würzburg
,
Sigrid Müller-Deubert
Bernhard-Heine-Centrum für Bewegungsforschung, Klinische und Experimentelle Osteologie, Universität Würzburg
,
Regina Ebert
Bernhard-Heine-Centrum für Bewegungsforschung, Klinische und Experimentelle Osteologie, Universität Würzburg
› Author Affiliations
Further Information

Publication History

11/07/2018

11/27/2018

Publication Date:
05 March 2019 (online)

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Zusammenfassung

PTH und PTHrP fördern situationsabhängig Knochenformation, -umbau und -abbau. Sie binden an den PTH Rezeptor Typ 1 (PTH1R) auf Osteoblasten, Osteozyten und T-Zellen und vermitteln Genregulation. Kurze Pulse wirken anabol, chronische Stimulation wirkt stark katabol. Teriparatid ist von PTH abgeleitet (Aminosäuren 1–34) und induziert Knochenformation, die durch mechanische Belastung auch an instabilen Stellen verstärkt wird. Klinische Endpunkte sind Zunahme an Knochenmasse und -struktur und deutliche Reduktion der Frakturrate der Wirbelkörper und – mit geringerer Effizienz – der non-vertebralen Frakturen. Die Wirkung ist in einem umfangreichen Studienprogramm in randomisierten kontrollierten und „Real-Life“-Studien evidenzbasiert belegt. Teriparatid wirkt bei Frauen und Männern, unter Glukokortikoid-Therapie und nach Bisphosphonat-Vorbehandlung. Es kann nur einmalig über 24 Monate verabreicht werden, nachfolgende Gabe von Antiresorptiva verbessert den Outcome. Gesundheitspolitische Vorgaben beschränken seine Anwendung in Deutschland auf die Situation neuer Frakturen unter Antiresorptiva. Teriparatid ist sicher, hat ein sehr gutes Nebenwirkungsprofil und ist das erste Beispiel einer Regenerativen Therapie in der Osteologie.

Abstract

PTH and PTHrP, critically depending on (patho-)physiological circumstances, stimulate bone formation, bone remodelling or bone resorption. Their specific binding to the G-protein-coupled receptor PTH1R on osteoblasts, osteocytes and T-cells elicits gene regulation in the target cells (e. g. via cAMP, proteinkinase C and ERK1/2-activation). Short and intermittent pulses initiate anabolic effects while chronic overstimulation causes substantial bone resorption. The duration of pulses may be modulated by pharmacological or intrinsic means on and within target cells. Teriparatide is an anabolic PTH-derived (amino acid 1–34) polypeptide that opens the anabolic window of PTH-signalling upon intermittent application. Teriparatide given as a subcoutaneous injection of 20 µg/day induces bone formation and tissue regeneration that is mechanically triggered and is especially effective in fragile bone regions. It is the only compound with substantial remodelling activity that is presently available for osteoporosis treatment. Teriparatide application increases bone mass and structure and as clinical endpoints enhances fracture resistance and reduces the rates of vertebral fractures and – albeit with some delay and somewhat lower efficacy – also non-vertebral fractures. The efficacy of teriparatide has been demonstrated in a huge program of clinical studies, comprising both randomized controlled trials and highly sophisticated observational studies that reflect efficacy under conditions of real life. Teriparatide can only be given for 24 months once in a lifetime. It is effective in women and men, under glucocorticoid treatment and after bisphosphonate pretreatment. Sequential treatment with antiresorptive compounds considerably enhances and prolongs the positive effects on clinical outcome parameters. In Germany considerations of health policy render this treatment a second line regimen after inadequate outcome using antiresorptives. Teriparatide is safe and shows a favorable profile of side effects. It represents the first example of a regenerative medicine approach in metabolic bone diseases.

Schlüsselwörter

Teriparatid - Osteoporose - anabole Therapie - Frakturen

Key words

Teriparatide - Osteoporosis - anabolic treatment - fractures
 

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