Osteoporose und Genetik des Knochenstoffwechsels

Zusammenfassung

Die Osteoporose wird definiert als eine systemische Skeletterkrankung mit niedriger Knochenmasse und einem Verlust der normalen Mikroarchitektur, woraus eine erhöhte Knochenbrüchigkeit und vermehrte Frakturgefährdung folgen. Dabei ist die klinisch manifeste Osteoporose der Endzustand einer zunächst klinisch inapparenten, im weiteren Verlauf jedoch progredienten Verminderung von Knochenmasse und -dichte, der Osteopenie. Bis dato existieren nur Diagnostika, die einen Status quo der Erkrankung widerspiegeln. Von hohem klinischen Interesse wären zukünftig jedoch prädiktive Parameter. Familien- und Zwillingsstudien belegen, dass die Osteoporose in hohem Maß genetisch determiniert ist. Die Forschung zur Aufdeckung der genetischen Basis der Osteoporose bzw. des Knochenstoffwechsels allgemein hat sich insbesondere in den letzten Jahren etabliert, die Untersuchungen zu potenziellen Genen und Polymorphismen sind aktuell jedoch eher von wissenschaftlichem Interesse und noch ohne klinische Relevanz. Das Vitamin-D-Rezeptor-Gen ist der am besten untersuchte molekulare Marker für die Genese der Osteoporose. Polymorphismen anderer Kandidatengene wie Hormonrezeptor-, Zytokin- oder Kollagen-Gene sind hinsichtlich Gen-Gen- und Gen-Umwelt-Interaktionen von wissenschaftlichem Interesse. Die Suche nach genetischen Faktoren des bei der Osteoporose gestörten Knochenstoffwechsels wird es zukünftig möglicherweise ermöglichen, potenzielle Wege zur Diagnostik, Prävention (über die Prädiktion eines Erkrankungsrisikos) und auch in der Therapie (aus den molekularen und biochemischen Funktionen der beteiligten Gene) zu entwickeln.

Abstract

Osteoporosis is a systemic skeletal disorder affecting bone mass and bone structure, with increased bone fragility and fracture risk. The clinical state of manifest osteoporosis is the final outcome of an initially inapparent, yet progressive reduction of bone mineral density and bone mass, osteopenia. To date, existing diagnostic methods reflect only the current state of the disease. Future predictive parameters, would however be of great clinical value. Osteoporosis exhibits a substantial genetic component as revealed by prevalence studies in families and twins. Genetic research on osteoporosis and bone metabolism, has been well established in recent years. So far however, research on potential genes and polymorphisms is chiefly of scientific interest without clinical relevance. The Vitamin D receptor gene has been shown to be a molecular marker, correlating with the development of osteoporosis. Other candidate gene polymorphisms such as hormone receptor, cytokine and collagen genes are currently being analysed regarding complex gene-gene and gene-environment interactions. Research on genetic factors for bone metabolism disorders in osteoporosis is still at its beginning, but we are looking forward to important new insights into skeletal pathophysiology that will contribute to new terms of prevention (predictive risk factors), diagnosis and treatment (biochemical and molecular gene function) of osteoporosis.

Schlüsselwörter

Osteoporose - Knochendichte - Genetik - molekulare Medizin

Key words

Osteoporosis - bone density - genetics - molecular medicine

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