Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma.
OBJECTIVE
Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. So far, there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions.


METHODS
DKK-1 serum levels were quantified in 184 untreated MM patients and 33 monoclonal gammopathy of undetermined significance (MGUS) patients by ELISA, using a monoclonal anti-DKK-1 antibody.


RESULTS
Serum DKK-1 was elevated in MM as compared with MGUS (mean 11 963 pg/mL vs. 1993 pg/mL; P < 0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL vs. 15 209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL vs. 17 915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1-3 vs. >3 lesions: 3114 pg/mL vs. 3559 pg/mL vs. 24 068 pg/mL; P = 0.002).


CONCLUSIONS
Using a large series of myeloma patients, we could show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, indicating that DKK-1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.
Kaiser
Martin
M
Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Mieth
Maren
M
Liebisch
Peter
P
Oberländer
Romy
R
Rademacher
Jessica
J
Jakob
Christian
C
Kleeberg
Lorenz
L
Fleissner
Claudia
C
Braendle
Edgar
E
Peters
Malte
M
Stover
David
D
Sezer
Orhan
O
Heider
Ulrike
U
D000328:Adult; D000368:Aged; D001847:Bone Diseases / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000473:pathology*
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins