This is not the most recent version of the article. View current version (16 MAY 2012)
Intervention Review
Bisphosphonates in multiple myeloma
Editorial Group: Cochrane Haematological Malignancies Group
Published Online: 21 JAN 2009
Assessed as up-to-date: 30 MAY 2002
DOI: 10.1002/14651858.CD003188
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Database Title
Additional Information
How to Cite
Djulbegovic B, Wheatley K, Ross H, Clark OAC, Bos G, Goldschmidt H, Cremer F, Alsina M, Glasmacher A. Bisphosphonates in multiple myeloma. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD003188. DOI: 10.1002/14651858.CD003188.
Publication History
- Publication Status: Edited (no change to conclusions)
- Published Online: 21 JAN 2009
This is not the most recent version of the article.View current version (16 May 2012)
Abstract
Background
Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction. Bisphosphonates are specific inhibitors of osteoclastic activity. Therefore, there is a pharmacological basis for their use in multiple myeloma. However, the exact clinical role of bisphosphonates in multiple myeloma remains unclear.
Objectives
Primary: to determine whether adding bisphosphonates to standard therapy in multiple myeloma decreases skeletal-related morbidity (pathological fractures), skeletal-related mortality and overall mortality. Secondary: to determine the effects of bisphosphonates on pain, quality of life and incidence of hypercalcemia.
Search strategy
We searched MEDLINE (1966 to June 2001), LILACS (1982 to June 2001), EMBASE (1974 to December 2000) and the Cochrane Controlled Trials Register (all years, latest Issue 03/2001) to identify all randomized trials in multiple myeloma. All of these references were accessed in order to identify trials related to the use of bisphosphonates in myeloma. All relevant references in each article were also scanned. We also performed a handsearch of relevant meeting proceedings from 1993 to 2000. Additionally, manufacturers of bisphosphonates and researchers in the field were contacted.
Selection criteria
Randomized trials with a parallel design on the use of bisphosphonate in myeloma compared with placebo or no treatment as a control group.
Data collection and analysis
Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. A third reviewer checked all data after the extraction was completed. Statistical heterogeneity was tested using random and fixed effect models. All pooled data are reported using Peto odds ratios and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event.
Main results
Eleven trials were included with 1113 patients analyzed in bisphosphonates groups, and 1070 analyzed in control groups. There was no significant statistical heterogeneity among trials for the endpoints selected for comparison in this review. The pooled analysis of the published evidence demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures [OR=0.59 (95% confidence interval (CI) 0.45 to 0.78); P = 0.0001] and on amelioration of pain [OR = 0.59 (95% CI 0.46 to 0.76); P = 0.00005]. However, the analysis of the effect of bisphosphonates on pain was based on clinically heterogeneous data and must be interpreted with caution. Although there was no statistical heterogeneity between groups, the benefit was most apparent with clodronate and pamidronate. In absolute terms, the result may be interpreted to mean that 10 (95% CI 7 to 20) patients with multiple myeloma should be treated to prevent one vertebral fracture, and 11 (95% CI 7 to 28) to prevent one patient experiencing pain. We found no significant effect of bisphosphonates on mortality, on the reduction of non-vertebral fractures or on the incidence of hypercalcemia. There were no significant adverse effects associated with the administration of bisphosphonates. Our results are based on the extraction of published data, which were sometimes poorly reported, and thus the results should be understood as the best possible summation of available evidence.
Authors' conclusions
Adding bisphosphonates to the treatment of myeloma reduces pathological vertebral fractures and pain but - from the published evidence - not mortality. On current evidence, clodronate or pamidronate may be the preferred agents.
Plain language summary
Bisphosphonates in Multiple Myeloma
Bisphosphonate drugs reduce pain and bone fractures in people with multiple myeloma, with clodronate and pamidronate helping most Multiple myeloma is cancer of the bone marrow. It causes bone destruction that leads to pain, spinal cord compression and fractures. Osteoclasts are cells that absorb bone. The bone destruction from myeloma is related to an abnormal increase in this resorption. The progression of this disease is not stopped by chemotherapy (anti-cancer drugs). Bisphosphonates are drugs that can inhibit bone resorption by reducing the number and activity of osteoclasts. The review of trials found that adding bisphosphonates (particularly clodronate or pamidronate) to myeloma treatment reduces breaks in the vertebra (bones in the spine), pain and hypercalcemia (too much calcium in the blood).