The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRANKL/osteoprotegerin ratio

Leukemia. 2005 Nov;19(11):1969-76. doi: 10.1038/sj.leu.2403890.


The aim of this study was the evaluation of the effect of intermediate doses of thalidomide with dexamethasone (Thal/Dex) on disease course and bone disease in patients with refractory/relapsed myeloma who were under zoledronic acid therapy. We studied 35 patients, who received thalidomide at a dose of 200 mg/daily. We measured, pre-, 3 and 6 months post-treatment soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), osteoprotegerin (OPG), osteopontin (OPN), markers of bone resorption and formation. Before treatment, patients had increased levels of sRANKL/OPG ratio, bone resorption markers and OPN, while they had suppressed bone formation. The pretreatment sRANKL/OPG ratio correlated with the extent of bone disease. Thal/Dex administration resulted in a significant reduction of sRANKL/OPG ratio, and bone resorption. Bone formation, OPG and OPN did not show any alteration. Changes of sRANKL/OPG ratio correlated with changes of bone resorption markers. Thal/Dex was given for a median time of 10 months and the median follow-up period was 22 months. The response rate was 65.7%. The median survival was 19.5 months. beta2-microglobulin, type of response and International Staging System predicted for survival. These results suggest that the combination of intermediate dose of Thal/Dex is effective in patients with refractory/relapsed myeloma and improves abnormal bone remodeling through the reduction of sRANKL/OPG ratio.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers / analysis
  • Bone Remodeling / drug effects*
  • Bone Remodeling / genetics
  • Dexamethasone / administration & dosage
  • Dose-Response Relationship, Drug
  • Female
  • Glycoproteins / analysis*
  • Humans
  • Ligands
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / physiopathology
  • Osteopontin
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear / analysis*
  • Receptors, Tumor Necrosis Factor / analysis*
  • Sialoglycoproteins / analysis
  • Survival Analysis
  • Thalidomide / administration & dosage


  • Biomarkers
  • Glycoproteins
  • Ligands
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • SPP1 protein, human
  • Sialoglycoproteins
  • TNFRSF11B protein, human
  • Osteopontin
  • Thalidomide
  • Dexamethasone