Serum concentrations of DKK‐1 correlate with the extent of bone disease in patients with multiple myeloma
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.
Document Type: Research Article
Affiliations: 1: Department of Hematology and Oncology, Charité– Universitätsmedizin Berlin, Berlin, Germany 2: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany 3: Novartis Institutes for Biomedical Research, Cambridge, MA, USA 4: Novartis Pharma, Basel, Switzerland
Publication date: June 1, 2008