title: Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance.
abstract: OBJECTIVE
  To determine whether various markers of bone turnover and/or plasma cytokines differ in patients with multiple myeloma (MM) compared with patients with monoclonal gammopathies of undetermined significance (MGUS).
  
  
  METHODS
  We studied 22 MM patients and 18 MGUS patients presenting over an 18-month period and compared their data with those from 20 age- and sex-matched patients presenting with primary osteoporosis. According to the Salmon and Durie classification, there were eight patients with stage I, nine with stage II and five with stage III disease. All patients had densitometric evidence of osteoporosis and were classified according to bone marrow evidence of plasma cell dyscrasia. Measured variables included markers of bone formation and bone resorption, and plasma cytokines.
  
  
  RESULTS
  Patients with MM and MGUS did not differ with respect to their mean age, male : female sex ratio, height, weight, serum calcium, 25-hydroxyvitamin D and parathyroid hormone concentrations. Patients with MM had significantly lower concentrations of haemoglobin (109 vs 135 g/L) and serum transforming growth factor (TGF)-beta (261 vs 348 pg/mL) than patients with MGUS, and higher concentrations of serum paraproteins (31.1 vs 7.4 g/L), beta2-microglobulin (3.5 vs 2.2 g/L), % plasma cell numbers (35.3 vs 2.1%) and urinary deoxypyridinoline excretion rates (u-DPYD; 7.7 vs 5.9 nmol/mmol creatinine; P < 0.05 for all comparisons). In multivariate analysis, the serum paraprotein (beta coefficient = -0.067; 95% confidence intervals (CI), -0.019 to -0.005; P = 0.0012), u-DPYD excretion rates (beta coefficient = -0.012; 95% CI, -0.113 to -0.02; P= 0.0058) and serum TGF-beta concentrations (beta coefficient = -0.002; 95% CI, -0.0002 to -0.02; P= 0.02) were the most important variables differentiating between MM and MGUS, after excluding lytic bone lesions, % plasma cell numbers and haemoglobin concentrations.
  
  
  CONCLUSIONS
  The well-established criteria for diagnosing MM include the presence of lytic bone lesions, plasmacytosis, haemoglobin and paraprotein concentrations. The u-DPYD excretion rate, a sensitive non-invasive marker of bone resorption, may help in differentiating between MM and MGUS, as well as serving as a marker of underlying bone disease activity in these patients.
authors.affiliation: Department of Endocrinology, St George Hospital, University of New South Wales, Sydney, Australia. terrydiamond@optushome.com.au
authors.forename: T
authors.initials: T
authors.lastname: Diamond
authors.forename: S
authors.initials: S
authors.lastname: Levy
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Day
authors.forename: A
authors.initials: A
authors.lastname: Manoharan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000150:complications; D015999:Multivariate Analysis; D010024:Osteoporosis / Q000097:blood* / Q000209:etiology; D010265:Paraproteinemias / Q000097:blood* / Q000150:complications
chemical_list: D015415:Biomarkers; D016207:Cytokines