Zusammenfassung
Die erhöhte Knochenresorption ist ein Hauptmerkmal des multiplen Myeloms und kann
die Lebensqualität der Patienten maßgeblich beeinträchtigen. Bei der überwiegenden
Mehrzahl der Myelompatienten sind Osteolysen festzustellen, die Schmerzen auslösen
und ein erhöhtes Frakturrisiko verursachen. Die Knochendestruktion entsteht beim multiplen
Myelom durch ein gestörtes Gleichgewicht der Aktivität der knochenaufbauenden Osteoblasten
und der knochenabbauenden Osteoklasten. Die zellulären Interaktionen sowie Dysregulation
von Zytokinen im Knochenmarkmikroenvironment sind an der Knochendestruktion beteiligt.
Die Behandlung mit Bisphosphonaten hemmt zwar die osteoklasteninduzierte Knochenresorption,
ist aber nicht in der Lage, die beim multiplen Myelom beobachtete Hemmung der Differenzierung
der mesenchymalen Stammzellen zu Osteoblasten auszugleichen. Bortezomib ist die wirksamste
Einzelsubstanz in der Therapie des multiplen Myeloms. Präklinische Untersuchungen
zeigen, dass der Proteasominhibitor Bortezomib darüber hinaus der myelominduzierten
Knochendestruktion entgegenwirken kann. Bortezomib hemmt einerseits die Osteoklastenaktivität
und fördert andererseits die Osteoblastenfunktion und weist somit Eigenschaften auf,
die für die Therapie der Knochenbeteiligung beim multiplen Myelom ideal erscheinen.
Bortezomib könnte somit nicht nur in der Behandlung gegen die Tumorzellen, sondern
auch in der Behandlung der Knochendestruktion eine wesentliche Rolle spielen. Klinische
Studien sind jedoch notwendig, um diese Effekte hinsichtlich ihrer klinischen Relevanz
zu untersuchen. Internationale prospektive klinische Studien wurden begonnen, um dies
in einem randomisierten Studiendesign zu untersuchen.
Abstract
Increased bone resorption is one of the main characteristics of multiple myeloma and
can considerably impair the quality of life of the patients. The vast majority of
myeloma patients have lytic bone lesions which lead to pain and an increased risk
of fractures. Bone destruction in multiple myeloma patients is caused by an imbalance
of the activity of bone-building osteoblasts and bone-resorbing osteoclasts. Cellular
interactions, as well as dysregulation of cytokines in the bone marrow microenvironment
are involved in bone destruction. Treatment with bisphosphonates inhibits osteoclast-induced
bone resorption, but it cannot compensate for the inhibited differentiation of mesenchymal
stem cells into osteoblasts observed in multiple myeloma patients. Bortezomib is the
most efficient single substance for the treatment of multiple myeloma. Preclinical
tests show that the proteasome inhibitor Bortezomib can furthermore counteract the
myeloma-induced bone destruction. On the one hand, Bortezomib inhibits osteoclast
activity and, on the other hand, promotes osteoblast function and thus has properties
that seem to be ideal for the therapy of bone disease in multiple myeloma patients.
Bortezomib might play an important part not only in the treatment against the tumour
cells, but also in the treatment of bone destruction. However, clinical studies have
to be carried out in order to examine these effects with a view to their clinical
relevance. International prospective randomized clinical trials have already been
started.
Schlüsselwörter
Bortezomib - Knochen - multiples Myelom - Osteoblasten - Osteoklasten - Proteasom
Key words
Bortezomib - bones - multiple myeloma - osteoblasts - osteoclasts - proteasome
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Prof. Dr. Orhan Sezer
Hämatologie und Onkologie, Charité – Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Phone: ++ 49/30/4 50 61 31 05
Fax: ++ 49/30/4 50 52 79 07
Email: sezer@charite.de
