Multiple myeloma (also known as myeloma or plasma cell myeloma) is a B-cell malignancy, or more precisely, plasma cell neoplasm. Multiple myeloma cells migrate to the bone marrow and continuously multiply. Thus, the cancer grows inside or outside of the bones. The bone damage, or osteolytic lesions, may lead to fractures of the long bones or compression fractures in the spine. The mechanism of bone destruction appears to be related to increased bone resorption by cells called osteoclasts. Bisphosphonates are drugs that can inhibit bone resorption by reducing the number and activity of osteoclasts. The review of trials shows that adding bisphosphonates to myeloma treatment reduces fractures of the vertebra (bones in the spine) and bone pain.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 7, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Mhaskar R, Redzepovic J, Wheatley K, Clark OAugusto Camara, Miladinovic B, Glasmacher A, Kumar A, Djulbegovic B. Bisphosphonates in multiple myeloma. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No.: CD003188. DOI: 10.1002/14651858.CD003188.pub2

Editorial Group: Haematological Malignancies Group

This version first published online: October 23. 2001
Last assessed as up-to-date: January 1. 2009

Abstract

Background

Bisphosphonates are specific inhibitors of osteoclastic activity and are currently used as supportive therapy for multiple myeloma (MM). However, the exact clinical role of bisphosphonates in MM remains unclear.

Objectives

This update of the first review published in 2002. We have also analyzed observational studies targeting osteonecrosis of jaw (ONJ).

Search strategy

We searched the literature using the methods outlined in the previous review. We also searched observational studies or case reports examining ONJ.

Selection criteria

We selected RCTs with a parallel design related to the use of bisphosphonate in myeloma. We also selected observational studies or case reports examining bisphosphonates related to ONJ.

Data collection and analysis

We have reported pooled data using either hazard ratio or risk ratio and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. We have assessed statistical heterogeneity and reported I² statistic.

Main results

This review includes 17 trials with 1520 patients analyzed in bisphosphonates groups, and 1490 analyzed in control groups. In comparison with placebo/no treatment, the pooled analysis demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures (RR= 0.74 (95% CI: 0.62 to 0.89), P = 0.001), total skeletal related events (SREs) (RR= 0.80 (95% CI: 0.72 to 0.89), P < 0.0001) and on amelioration of pain (RR = 0.75 (95% CI: 0.60 to 0.95), P = 0.01). We found no significant effect of bisphosphonates on overall survival (OS), progression-free survival (PFS), hypercalcemia or on the reduction of non-vertebral fractures. The indirect meta-analyses did not find the superiority of any particular type of bisphosphonate over others. Only two RCTs reported ONJ. The identified observational studies suggested that ONJ may be a common event (range: 0% to 51%).

Authors' conclusions

Adding bisphosphonates to the treatment of MM reduces pathological vertebral fractures, SREs and pain but not mortality. Assuming the baseline risk of 20% to 50% for vertebral fracture without treatment, we estimate that between eight and 20 MM patients should be treated to prevent vertebral fracture(s) in one patient. Assuming the baseline risk of 31% to 76% for pain amelioration without treatment, we estimate that between five to 13 MM patients should be treated to reduce pain in one patient. Also, with the baseline risk of 35% to 86% for SREs without treatment, we estimate that between six and 15 MM patients should be treated to prevent SRE(s) in one patient. No bisphoshphonate appears to be superior to others.

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