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Related Experiment Video

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Bisphosphonates in multiple myeloma: a network meta-analysis.

Rahul Mhaskar1, Jasmina Redzepovic, Keith Wheatley

  • 1Center for Evidence Based Medicine and Health Outcomes Research, University of South Florida, Tampa, Florida, USA.

The Cochrane Database of Systematic Reviews
|May 18, 2012
PubMed
Summary

Bisphosphonates effectively reduce vertebral fractures, pain, and skeletal-related events in multiple myeloma (MM) patients. While not improving overall survival (OS) directly, zoledronate shows a potential OS benefit compared to placebo and etidronate.

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Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Bisphosphonates inhibit osteoclastic activity and are used in multiple myeloma (MM) treatment.
  • Their efficacy in reducing fractures and pain is established, but impact on overall survival (OS) is unclear.
  • This review updates previous Cochrane analyses on bisphosphonate use in MM.

Purpose of the Study:

  • To evaluate benefits and harms of bisphosphonates (amino- vs. non-aminobisphosphonates) in MM management.
  • Primary objectives: assess impact on OS, progression-free survival (PFS), and skeletal-related morbidity.
  • Secondary objectives: evaluate effects on pain, quality of life, hypercalcemia, GI toxicities, osteonecrosis of the jaw (ONJ), and hypocalcemia.

Main Methods:

  • Searched MEDLINE, LILACS, EMBASE, and Cochrane Controlled Trials Register up to October 2011.
  • Included randomized controlled trials (RCTs) and observational studies/case reports for ONJ.
  • Data pooled using random-effects models (hazard ratio/risk ratio); heterogeneity explored via metaregression.

Main Results:

  • Pooled analysis showed no direct effect of bisphosphonates on OS (HR 0.96).
  • Significant heterogeneity for OS suggested a potential benefit with zoledronate (P=0.058).
  • Bisphosphonates significantly reduced vertebral fractures (RR 0.74), skeletal-related events (SREs) (RR 0.80), and pain (RR 0.75). No significant increase in GI symptoms or hypocalcemia.
  • Network meta-analysis indicated superior OS with zoledronate versus etidronate and placebo.
  • No differences in ONJ incidence between bisphosphonates in RCTs; rates varied widely in observational studies.

Conclusions:

  • Bisphosphonates effectively reduce pathological vertebral fractures, SREs, and pain in MM patients.
  • Zoledronate demonstrated superiority over placebo and etidronate for improving overall survival.
  • No significant adverse effects identified; no superiority found for other specific bisphosphonates over each other.