Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma.
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Kaiser, Martin, Mieth, Maren, Liebisch, Peter, Oberlaender, Romy, Rademacher, Jessica, Jakob, Christian, Kleeberg, Lorenz, Fleissner, Claudia, Braendle, Edgar, Peters, Malte, Stover, David, Sezer, Orhan and Heider, Ulrike (2008) Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. European Journal of Haematology, 80 (6). pp. 490-494. ISSN 1600-0609
Abstract
OBJECTIVES: 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). CONCLUSION: 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.
| Item Type: | Article |
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| Keywords: | Dickkopf-1; multiple myeloma; bone; osteoblast; osteoclast |
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| Date Deposited: | 14 Dec 2009 13:52 |
| Last Modified: | 31 Jan 2013 01:05 |
| URI: | https://oak.novartis.com/id/eprint/857 |