Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy

J Clin Oncol. 2005 Aug 1;23(22):5217-23. doi: 10.1200/JCO.2005.11.676. Epub 2005 Jun 13.

Abstract

Purpose: To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.

Patients and methods: A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period.

Results: With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones.

Conclusion: AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dexamethasone / administration & dosage
  • Female
  • Femur Head Necrosis / epidemiology
  • Femur Head Necrosis / etiology*
  • Femur Head Necrosis / pathology*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-alpha / administration & dosage
  • Male
  • Middle Aged
  • Multiple Myeloma / complications*
  • Multiple Myeloma / drug therapy*
  • Odds Ratio
  • Prevalence
  • Risk Factors
  • Sex Factors
  • Stem Cell Transplantation
  • Thalidomide / therapeutic use*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Interferon-alpha
  • Thalidomide
  • Dexamethasone