title: Prospective study of signalling pathways in myeloma bone disease with regard to activity of the disease, extent of skeletal involvement and correlation to bone turnover markers.
abstract: OBJECTIVE
  The aim of our study was to address the utility of serum levels of selected parameters of myeloma bone disease (MBD) signalling with regard to the pathogenesis of multiple myeloma (MM), activity, markers of bone turnover and extent of skeletal changes.
  
  
  METHODS
  We assessed prospectively 77 individuals with monoclonal gammopathies - 46 patients with active MM (AMM), 12 patients with smouldering MM (SMM) and 19 individuals with monoclonal gammopathy of undetermined significance (MGUS) to determine the role of HGF, MIP-1α, Syndecan-1, osteoprotegerin, Activin A, DKK1, Annexin A2 and NF-κB.
  
  
  RESULTS
  We found significant differences of most of the parameters between MGUS and AMM, and with respect to the activity of MM assessed by International Staging System. Most of the parameters of MBD signalling correlated with traditional markers of bone turnover.
  
  
  CONCLUSIONS
  All the signalling pathways were activated in MM with more pronounced osteoclastogenesis in comparison with bone formation but not in MGUS regardless of its risk category, suggesting that MBD is not activated in MGUS until the process of transformation into MM. The parameters of MBD signalling might precede the increase of conventional parameters of bone turnover suggesting their possible role in early indication of anti-resorption therapy.
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Minarik
authors.affiliation: Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hermanova
authors.affiliation: Department of Clinical Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Petrova
authors.affiliation: Department of Radiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hrbek
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Zapletalova
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Krhovska
authors.affiliation: Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Patrik
authors.initials: P
authors.lastname: Flodr
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Pika
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Bacovsky
authors.affiliation: Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Flodrova
authors.affiliation: Department of Radiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Herman
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Scudla
mesh_terms: D015415:Biomarkers; D001847:Bone Diseases / Q000175:diagnosis* / Q000209:etiology*; D016723:Bone Remodeling; D005260:Female; D006801:Humans; D008297:Male; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications / Q000175:diagnosis; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism*; D010265:Paraproteinemias / Q000150:complications / Q000175:diagnosis; D011446:Prospective Studies; D015398:Signal Transduction
chemical_list: D015415:Biomarkers
keywords: bone turnover markers; imaging techniques; multiple myeloma; myeloma bone disease; signalling