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Aktuelle Rheumatologie 2012; 37(04): 228-237
DOI: 10.1055/s-0032-1306339
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Evidenz von Bisphosphonaten bei entzündlich-rheumatischen Erkrankungen

Evidence in Favour of Bisphosphonates for Inflammatory Rheumatic Diseases
P. Oelzner
1    Klinik für Innere Medizin III, Universitätsklinikum Jena, Jena
,
G. Wolf
2    Medizinische Klinik III, Friedrich-Schiller-Universität Jena, Nephrologie, Jena
› Author Affiliations
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Publication History

Publication Date:
17 July 2012 (online)

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Zusammenfassung

Die häufigsten entzündlich-rheumatischen Erkrankungen, Rheumatoide Arthritis (RA), ankylosierende Spondylitis und Arthritis psoriatica als auch das seltene SAPHO-Syndrom gehen in der Regel mit Knochendestruktion bzw. Veränderungen des Knochenumbaus einher. Insbesondere im Fall der RA kommt es häufig zu einer systemischen Osteoporose. Aus diesem Grunde sind für die Behandlung der genannten Erkrankungen Medikamente, welche sowohl die Knochenresorption und den Knochenumbau hemmen als auch potentiell in der Lage sind, entzündliche Prozesse zu supprimieren, von besonderem Interesse. Basierend auf den Ergebnissen Plazebo-kontrollierter Studien haben Bisphosphonate einen festen Platz in der Prävention und Therapie des Glukokortikoid-begünstigten Knochenmasseverlustes bei entzündlich-rheumatischen Erkrankungen und können das Frakturrisiko in diesem Zusammenhang reduzieren. Eine Hemmung der Destruktion des periartikulären Knochens bei der RA ist dagegen offensichtlich nicht mit den in der Osteoporose-Therapie üblichen Dosierungen der meisten Bisphosphonate möglich und gelingt nur mit dem hoch potenten intravenösen Bisphosphonat Zoledronat. Für andere Bisphosphonate sind zur Suppression von Destruktion und entzündlicher Aktivität im Arthritis-Modell Dosierungen notwendig, welche die beim Menschen übliche Dosis überschreiten. Zoledronat bewirkte bei Arthritis psoriatica eine Reduktion des die Osteitis reflektierenden Knochenmarködems, jedoch keine Hemmung der Knochen-Erosion. Bei ankylosierender Spondylitis und SAPHO-Syndrom konnte insbesondere für Pamidronat im Rahmen von offenen Studien eine Reduktion der entzündlichen Aktivität und Wirbelsäulen-Funktion repräsentierenden Scores sowie teilweise auch der paraklinischen Entzündungsparameter nachgewiesen werden. Unterschiedliche molekulare Mechanismen des systemischen und gelenknahen Knochenmasseverlustes sowie des Knochenumbaus bei RA einerseits sowie ankylosierender Spondylitis und SAPHO-Syndrom andererseits dürften für die differente Wirksamkeit von Bisphosphonaten im Hinblick auf Entzündung und Entzündungs-assoziierte Knochenveränderungen verantwortlich sein.

Abstract

The most common inflammatory rheumatic diseases, i. e., rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis as well as SAPHO syndrome are regularly associated with bone destruction or disturbance of bone turnover. Especially in rheumatoid arthritis, systemic osteoporosis frequently occurs. Therefore, drugs that suppress bone resorption as well as bone turnover and potentially reduce inflammatory processes are of critical interest in the treatment of these diseases. Based on the results of randomised, placebo-controlled trials, bisphosphonates are the treatment of choice in the prevention of and therapy for glucocorticoid-induced osteoporosis in inflammatory rheumatic diseases including the reduction of fracture risk. In contrast, an inhibition of destruction of periarticular bone in rheumatoid arthritis is not possible using the normal doses for treatment of osteoporosis of most bisphosphonates, except for the highly potent intravenous bisphosphonate zoledronate. In animal models of rheumatoid arthritis high doses of different bisphosphonates are necessary for the suppression of bone destruction and inflammatory disease activity. Zoledronate reduces bone marrow oedema as a sign reflecting osteitis in psoriatic arthritis but is not able to prevent bone erosion. In the case of ankylosing spondylitis and the SAPHO syndrome, especially pamidronate has been shown to reduce different scores reflecting disease activity and function of the spine and also laboratory parameters of inflammation in part in different open-label studies. Different molecular mechanisms of systemic and periarticular bone loss and of bone turnover in rheumatoid arthritis on the one hand and in ankylosing spondylitis and SAPHO syndrome on the other may contribute to the different effectivity of bisphosphonates with respect to inflammation and inflammation-associated bone changes.

Schlüsselwörter

Entzündung - Knochendestruktion - Osteoporose - Bisphosphonate

Key words

inflammation - bone destruction - osteoporosis - bisphosphonates
 

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