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Two Year Randomized Controlled Trial of Etidronate in Rheumatoid Arthritis: Changes in Serum Aminoterminal Telopeptides Correlate with Radiographic Progression of Disease
HEIKKI VALLEALA, LEENA LAASONEN, MARJA-KAISA KOIVULA, JAMI MANDELIN, CLAES FRIMAN, JUHA RISTELI, and YRJÖ T KONTTINEN
ABSTRACT. Methods. Forty patients with RA of less than 5 years' duration were randomized to receive intermittent cyclical etidronate therapy in conjunction with antirheumatic therapy or antirheumatic therapy alone (without etidronate) in a 2 year open-label protocol. Radiographs of hands and feet and serum samples for determination of aminoterminal propeptide (PINP), crosslinked C-telopeptide (ICTP), and aminoterminal telopeptides (NTx) of type I collagen were obtained at baseline and at 24 months. Results. There was significant and similar worsening of the radiologic scores in both treatment groups. Both PINP, a marker of bone formation, and ICTP, an indicator of collagen degradation, declined in the etidronate group compared to the control group (p = 0.001 and p = 0.042, respectively). The groups did not differ for the change in serum NTx, a specific systemic marker of osteoclastic bone resorption. However, the change in serum NTx correlated significantly with the increase in erosion score in the total study population and in the control group (r = 0.41, p = 0.01 and r = 0.48, p = 0.034, respectively). Conclusion. Etidronate therapy did not prevent radiologic progression in patients with RA, but the decline in serum PINP and ICTP concentrations suggests a favorable effect on general bone metabolism. Correlation between the change in serum NTx and worsening of the erosion score provides biochemical evidence that osteoclast is the principal cell type responsible for focal bone resorption in RA. (J Rheumatol 2003;30:468-73) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Department of Medicine, the Department of Radiology and the Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital; Biomedicum/Anatomy, University of Helsinki; ORTON Research Institute, the Orthopaedic Hospital of the Invalid Foundation, Helsinki; and the Department of Clinical Chemistry, University of Oulu, Oulu, Finland. Supported by a grant from The Finnish Medical Society, by EVO research grant TYH 8307, EVO research months, and the Graduate School of Clinical Pharmacology. H. Valleala, MD; C. Friman, MD, PhD, Professor, Department of Medicine; L. Laasonen, MD, PhD, Department of Radiology, Helsinki University Central Hospital; J. Mandelin, MSc, Biomedicum/Anatomy, University of Helsinki; Y.T. Konttinen, MD, PhD, Professor, Department of Medicine/Invärtes Medicin, Helsinki University Hospital, ORTON Research Institute, Orthopaedic Hospital of the Invalid Foundation, Biomedicum/Anatomy, University of Helsinki; M-K. Koivula, MSc, PhD, MD; J. Risteli, MD, PhD, Professor, Department of Clinical Chemistry, University of Oulu. Address reprint requests to Dr. H. Valleala, Department of Medicine, Helsinki University Central Hospital, Kasarmikatu 11-13, FIN-00130 Helsinki, Finland. E-mail: heikki.valleala@hus.fi Submitted June 3, 2002; revision accepted September 11, 2002. |