title: Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma.
abstract: The effect of bortezomib on bone remodelling was evaluated in 34 relapsed myeloma patients. At baseline, patients had increased serum concentrations of dickkopf-1 (DKK-1), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of type-I collagen (CTX) and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b); bone-alkaline phosphatase and osteocalcin were reduced. Serum DKK-1 correlated with CTX and severe bone disease. Bortezomib administration significantly reduced serum DKK-1, sRANKL, CTX, and TRACP-5b after four cycles, and dramatically increased bone-alkaline phosphatase and osteocalcin, irrespective of treatment response. This is the first study showing that bortezomib reduces DKK-1 and RANKL serum levels, leading to the normalisation of bone remodelling in relapsed myeloma.
authors.affiliation: Department of Haematology and Medical Research, General Airforce Hospital, Athens, Greece. eterpos@hotmail.com
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Heath
authors.forename: Amin
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: Kostas
authors.initials: K
authors.lastname: Zervas
authors.forename: Andrew
authors.initials: A
authors.lastname: Chantry
authors.forename: Athanasios
authors.initials: A
authors.lastname: Anagnostopoulos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Pouli
authors.forename: Eirini
authors.initials: E
authors.lastname: Katodritou
authors.forename: Evgenia
authors.initials: E
authors.lastname: Verrou
authors.forename: Elisavet-Christine
authors.initials: EC
authors.lastname: Vervessou
authors.forename: Meletios-Athanassios
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Peter I
authors.initials: PI
authors.lastname: Croucher
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D010455:Peptides / Q000097:blood; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D053245:RANK Ligand / Q000097:blood*; D012008:Recurrence; D018709:Statistics, Nonparametric; D000071681:Tartrate-Resistant Acid Phosphatase; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D001897:Boronic Acids; D024042:Collagen Type I; C501126:DKK1 protein, human; D004164:Diphosphonates; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D053244:Osteoprotegerin; D010455:Peptides; D011480:Protease Inhibitors; D011719:Pyrazines; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D000069286:Bortezomib; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase