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.
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.
Terpos
Evangelos
E
Department of Haematology and Medical Research, General Airforce Hospital, Athens, Greece. eterpos@hotmail.com
Heath
Deborah J
DJ
Rahemtulla
Amin
A
Zervas
Kostas
K
Chantry
Andrew
A
Anagnostopoulos
Athanasios
A
Pouli
Anastasia
A
Katodritou
Eirini
E
Verrou
Evgenia
E
Vervessou
Elisavet-Christine
EC
Dimopoulos
Meletios-Athanassios
MA
Croucher
Peter I
PI
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
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