217 - DICKKOPF-1 protein levels in patients with monoclonal gammopathy of undetermined significance
Autor(s): R. Cardinali, D. Fiorentino, P. Capuani, L. Pappaccogli, G. Lobreglio
Issue: RIMeL - IJLaM, Vol. 5, N. 3, 2009 (MAF Servizi srl ed.)
Page(s): 217-21
Summary
Background. Dickkopf-1 (DKK-1) is a protein expressed by osteoblasts and osteocytes; it acts as soluble inhibitor of the WNT/β-catenin signaling pathway. DKK-1 is a crucial regulator of osteoblast growth and differentiation and has been involved in the regulation of bone metabolism. A raised bone resorption with an increased prevalence of vertebral fractures has been reported among patients with monoclonal gammopathy of undetermined significance (MGUS), but the mechanism of this bone loss is poorly understood. The aim of this study is to evaluate a possible role of DKK1, in the development of skeletal involvement in patients with MGUS. Methods. DKK-1 serum levels were quantified in 128 patient with MGUS (61 IgGk, 35 IgGλ, 9 IgAk, 13 IgAλ; 8 IgMk; 2 IgMλ) (51 females, 77 males; mean age, 77 ± 16 years) and in 48 normal subjects by ELISA (Biomedica Medizinprodukte, Wien, Austria). None of the patients with MGUS had vertebral fracture or apparent radiographic evidence of osteolytic lesions. Results. The results show a significantly lower concentration of DKK-1 among patients with MGUS (11.4 ± 7.9 pmol/l) compared to normal subjects (22.1 ± 13.1 pmol/L; P <0.001). Conclusions. Osteoclast activation occurs through a variety of factors, including RANK-L, parathyroid hormone-related protein, interleukin-1 and macrophage protein 1-alpha, and has been implicated in the development of skeletal involvement in patients with multiple myeloma and MGUS. Our results suggest that the low expression of DKK-1 observed in patients with MGUS, might be determined by a feed-back loop to counteract the role of osteoclast-activating factors and thus compensate the increased bone resorption with new bone formation. Key-words: Dickkopf-1, monoclonal gammopathy of undetermined significance, receptor activator of nuclear factor-kB ligand, osteoprotegerin.