Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and beta 2-microglobulin in multiple myeloma.
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.
Terpos
Evangelos
E
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
Viniou
Nora
N
de la Fuente
Josu
J
Meletis
John
J
Voskaridou
Ersi
E
Karkantaris
Christos
C
Vaiopoulos
George
G
Palermos
John
J
Yataganas
Xenophon
X
Goldman
John M
JM
Rahemtulla
Amin
A
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
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