title: Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and beta 2-microglobulin in multiple myeloma.
abstract: OBJECTIVE
  Bisphosphonates have been found to reduce skeletal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, 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 radiotherapy 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 alkaline phosphatase and osteocalcin), markers of disease activity (paraprotein, CRP, beta 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 beta 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 beta 2-microglobulin in group I than in group II, starting at the second month of treatment (P = 0.002, 0.001, and 0.004, respectively) and of TRACP-5b, starting at the fourth month (P = 0.014), that being continued throughout the 10-month follow-up of this study. There was no difference in skeletal events during this period. A significant correlation was observed between changes of NTX and changes of TRACP-5b, IL-6, and beta 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.
authors.affiliation: Department of Haematology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. eterpos@hotmail.com
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Nora
authors.initials: N
authors.lastname: Viniou
authors.forename: Josu
authors.initials: J
authors.lastname: de la Fuente
authors.forename: John
authors.initials: J
authors.lastname: Meletis
authors.forename: Ersi
authors.initials: E
authors.lastname: Voskaridou
authors.forename: Christos
authors.initials: C
authors.lastname: Karkantaris
authors.forename: George
authors.initials: G
authors.lastname: Vaiopoulos
authors.forename: John
authors.initials: J
authors.lastname: Palermos
authors.forename: Xenophon
authors.initials: X
authors.lastname: Yataganas
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Amin
authors.initials: A
authors.lastname: Rahemtulla
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D015850:Interleukin-6 / Q000097:blood; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D010012:Osteogenesis / Q000187:drug effects; D000077268:Pamidronate; D010455:Peptides / Q000652:urine; D000071681:Tartrate-Resistant Acid Phosphatase; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D015850:Interleukin-6; D007527:Isoenzymes; D010455:Peptides; D001613:beta 2-Microglobulin; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D000077268:Pamidronate; D000077557:Ibandronic Acid