@article{3129666,
    title = "Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. Melphalan-prednisone in the phase III VISTA trial in multiple myeloma",
    author = "Delforge, M. and Terpos, E. and Richardson, P.G. and Shpilberg, O. and Khuageva, N.K. and Schlag, R. and Dimopoulos, M.A. and Kropff, M. and Spicka, I. and Petrucci, M.T. and Samoilova, O.S. and Mateos, M.-V. and Magen-Nativ, H. and Goldschmidt, H. and Esseltine, D.-L. and Ricci, D.S. and Liu, K. and Deraedt, W. and Cakana, A. and Van de Velde, H. and San Miguel, J.F.",
    journal = "European Journal of Haematology",
    year = "2011",
    volume = "86",
    number = "5",
    pages = "372-384",
    issn = "0902-4441, 1600-0609",
    doi = "10.1111/j.1600-0609.2011.01599.x",
    keywords = "alkaline phosphatase;  bisphosphonic acid derivative;  bortezomib;  dickkopf 1 protein;  melphalan;  prednisone, adult;  aged;  alkaline phosphatase blood level;  article;  bone disease;  bone metabolism;  bone remodeling;  cancer radiotherapy;  computer assisted tomography;  controlled study;  drug effect;  female;  fracture healing;  human;  hypercalcemia;  major clinical study;  male;  multiple cycle treatment;  multiple myeloma;  osteoblast;  phase 3 clinical trial;  priority journal;  randomized controlled trial;  skull radiography;  treatment response, Aged;  Aged, 80 and over;  Alkaline Phosphatase;  Antineoplastic Combined Chemotherapy Protocols;  Biological Markers;  Bone Diseases;  Bone Remodeling;  Boronic Acids;  Cell Differentiation;  Female;  Humans;  Intercellular Signaling Peptides and Proteins;  Male;  Melphalan;  Middle Aged;  Multiple Myeloma;  Osteoblasts;  Prednisone;  Pyrazines;  Radiotherapy, Adjuvant",
    abstract = "Objectives: Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment. Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3mg/m 2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9mg/m 2 and prednisone 60mg/m 2, days 1-4, cycles 1-9; N=344) or MP alone (N=338). Results: Rates of bisphosphonates use during treatment (73% vs. 82%), progression because of worsening bone disease (3% vs. 11%), and requirement for subsequent radiotherapy (3% vs. 8%) were lower with VMP vs. MP. Median maximum ALP increase was significantly higher with VMP vs. MP overall (49.7% vs. 30.3%, P=0.029), and higher by response group (complete response [CR]: 68.7% vs. 43.9%; partial response [PR]: 41.5% vs. 31.2%). Greater maximum ALP increase was strongly associated with achievement of CR (P≤0.0001) and CR/PR (P≤0.01). Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 (P=0.0069). Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients, who achieved best responses of three CR, one PR, and two stable disease. Conclusions: These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma. © 2011 John Wiley and Sons A/S."
}