Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and beta 2-microglobulin in multiple myeloma

Eur J Haematol. 2003 Jan;70(1):34-42. doi: 10.1034/j.1600-0609.2003.02823.x.


Objectives: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acid Phosphatase / blood
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Biomarkers / blood
  • Biomarkers / urine
  • Bone Resorption / drug therapy*
  • Bone Resorption / etiology
  • Bone Resorption / prevention & control
  • Collagen / urine
  • Collagen Type I
  • Diphosphonates / administration & dosage*
  • Female
  • Humans
  • Ibandronic Acid
  • Interleukin-6 / blood
  • Isoenzymes / blood
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy*
  • Osteogenesis / drug effects
  • Pamidronate
  • Peptides / urine
  • Tartrate-Resistant Acid Phosphatase
  • beta 2-Microglobulin / blood


  • Antineoplastic Agents
  • Biomarkers
  • Collagen Type I
  • Diphosphonates
  • Interleukin-6
  • Isoenzymes
  • Peptides
  • beta 2-Microglobulin
  • collagen type I trimeric cross-linked peptide
  • Collagen
  • ACP5 protein, human
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Pamidronate
  • Ibandronic Acid