International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma-Related Bone Disease

J Clin Oncol. 2013 Jun 20;31(18):2347-57. doi: 10.1200/JCO.2012.47.7901. Epub 2013 May 20.


Purpose: The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease.

Methodology: An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members.

Recommendations: Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

MeSH terms

  • Administration, Intravenous
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Diseases / complications
  • Bone Diseases / drug therapy*
  • Bone Diseases / radiotherapy
  • Clodronic Acid / administration & dosage
  • Clodronic Acid / therapeutic use
  • Combined Modality Therapy
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use
  • Drug Therapy, Combination
  • Fractures, Bone / diagnosis
  • Fractures, Bone / prevention & control
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use
  • International Cooperation
  • Magnetic Resonance Imaging
  • Medical Oncology / organization & administration
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / radiotherapy
  • Osteonecrosis / diagnosis
  • Osteonecrosis / prevention & control
  • Outcome Assessment, Health Care / methods
  • Pamidronate
  • Positron-Emission Tomography
  • Practice Guidelines as Topic*
  • Radiotherapy / methods
  • Tomography, X-Ray Computed
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Clodronic Acid
  • Zoledronic Acid
  • Pamidronate