Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma

Leukemia. 2004 Aug;18(8):1420-6. doi: 10.1038/sj.leu.2403423.


The osteoprotegerin (OPG)/receptor activator of NF-kappa B ligand (RANKL) system has a major role in the pathogenesis of bone disease in myeloma (MM). The effect of autologous stem cell transplantation (ASCT) on bone turnover in MM was evaluated in 51 patients (35M/16F). Markers of bone resorption (NTX, TRACP-5b), bone formation (bone-alkaline phosphatase (bALP), osteocalcin), OPG and sRANKL were measured pre- and every month post-ASCT. The median follow-up period was 12 months. Four patients were transplanted in CR, 44 were transplanted in PR and three patients had progressive/resistant disease. All patients received bisphosphonates both pre- and post-ASCT. At baseline the majority of patients had increased NTX, TRACP-5b levels, and sRANKL/OPG ratio, while markers of bone formation were strongly suppressed. ASCT produced a significant reduction of sRANKL/OPG ratio, with a concomitant decrease of NTX, and TRACP-5b levels, starting the second month post-ASCT. Bone formation markers, osteocalcin and bALP, started to increase after the 9th and 11th month post-ASCT, respectively, while the increase of OPG preceded this. These results provide biochemical evidence that ASCT normalizes the abnormal bone resorption in MM patients possibly through the decrease of RANKL/OPG ratio, while bone formation requires a longer period to return to normal.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Bone Diseases / etiology
  • Bone Diseases / therapy
  • Bone Remodeling*
  • Bone Resorption
  • Carrier Proteins / analysis
  • Case-Control Studies
  • Diphosphonates / therapeutic use
  • Female
  • Follow-Up Studies
  • Glycoproteins / analysis
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / physiopathology*
  • Multiple Myeloma / therapy*
  • Osteogenesis
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Tumor Necrosis Factor
  • Time Factors
  • Transplantation, Autologous


  • Biomarkers
  • Carrier Proteins
  • Diphosphonates
  • Glycoproteins
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human