title: Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma.
abstract: 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.
authors.affiliation: Department of Hematology, Faculty of Medicine Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.forename: M
authors.initials: M
authors.lastname: Politou
authors.forename: R
authors.initials: R
authors.lastname: Szydlo
authors.forename: E
authors.initials: E
authors.lastname: Nadal
authors.forename: S
authors.initials: S
authors.lastname: Avery
authors.forename: E
authors.initials: E
authors.lastname: Olavarria
authors.forename: E
authors.initials: E
authors.lastname: Kanfer
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.forename: A
authors.initials: A
authors.lastname: Rahemtulla
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001847:Bone Diseases / Q000209:etiology / Q000628:therapy; D016723:Bone Remodeling; D001862:Bone Resorption; D002352:Carrier Proteins / Q000032:analysis; D016022:Case-Control Studies; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D010012:Osteogenesis; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D004164:Diphosphonates; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human