Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and b 2 -microglobulin in multiple myeloma Multiple myeloma (MM) is a plasma cell malig- nancy characterised by osteolytic bone destruction, and patients may develop pathologic fractures, hypercalcaemia, and spinal cord compression (1). Skeletal destruction results from increased osteo- clastic activity, which is not accompanied by a comparable increase in bone formation and is mediated by cytokines, which are produced locally in the bone marrow microenvironment by cells of tumour or non-tumour origin (2). Bisphosphonates Terpos E, Viniou N, de la Fuente J, Meletis J, Voskaridou E, Karkantaris C, Vaiopoulos G, Palermos J, Yataganas X, Goldman JM, Rahemtulla A. Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and b 2 -microglobulin in multiple myeloma. Eur J Haematol 2003: 70: 34–42. Ó Blackwell Munksgaard 2003. Abstract: Objectives: Bisphosphonates have been found to reduce skel- etal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandro- nate, a third-generation aminobisphosphonate, in bone turnover and disease activity in MM patients. Methods: Patients with MM, stage II or III, were randomly assigned to receive either pamidronate 90 mg (group I: 23 patients) or ibandronate 4 mg (group II: 21 patients) as a monthly intravenous infusion in addition to conventional chemotherapy. Skeletal events, such as pathologic fractures, hypercalcaemia, and bone radio- therapy were analysed. Bone resorption markers [N-terminal cross- linking telopeptide of type-I collagen (NTX) and tartrate-resistant acid phosphatase type 5b (TRACP-5b)], bone formation markers (bone al- kaline phosphatase and osteocalcin), markers of disease activity (para- protein, CRP, b 2 -microglobulin), and interleukin-6 (IL-6) were also studied. Results: In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL-6, paraprotein, CRP, and b 2 -microglobulin from the second month of treatment, having no effect on bone formation. TRACP-5b also had a significant reduction in the pamidronate group from the second month of treatment and in the ibandronate group from the sixth month. However, there was a greater reduction of NTX, IL-6, and b 2 -microglobulin in group I than in group II, starting at the second month of treatment (P ¼ 0.002, 0.001, and 0.004, respectively) and of TRACP-5b, starting at the fourth month (P ¼ 0.014), that being continued throughout the 10-month follow-up of thisstudy.Therewasnodifferenceinskeletaleventsduringthisperiod.A significant correlation was observed between changes of NTX and changes of TRACP-5b, IL-6, and b 2 -microglobulin from the second month for patients of both groups. Conclusions: These results suggest that a monthly dose of 90 mg of pamidronate is more effective than 4 mg of ibandronate in reducing osteoclast activity, bone resorption, IL-6, and possibly tumour burden in MM. TRACP-5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM. Evangelos Terpos 1 , Nora Viniou 2 , Josu de la Fuente 1 , John Meletis 2 , Ersi Voskaridou 2 , Christos Karkantaris 3 , George Vaiopoulos 2 , John Palermos 4 , Xenophon Yataganas 2 , John M Goldman 1 , Amin Rahemtulla 1 1 Department of Haematology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, UK; 2 First Department of Medicine, University of Athens School of Medicine, Laikon General Hospital, Athens, Greece; Departments of 3 Haematology and 4 Immunology, 251 General Air Force Hospital, Athens, Greece Key words: pamidronate; ibandronate; multiple myeloma; tartrate-resistant acid phosphatase type 5b (TRACP-5b); N-terminal cross-linking telopeptide of type-I collagen (NTX); bone markers Correspondence: Evangelos Terpos, Department of Haematology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK Tel:/Fax: + 44 (0) 208 8963531 e-mail: eterpos@hotmail.com Accepted for publication 12 November 2002 Eur J Haematol 2003: 70: 34–42 Printed in UK. All rights reserved Copyright Ó Blackwell Munksgaard 2003 EUROPEAN JOURNAL OF HAEMATOLOGY ISSN 0902-4441 34