title: Prognostic value of the bone turnover markers in multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and reduced osteoblast function.
  
  
  OBJECTIVE
  The aim of our research was to determine connection between bone turnover markers and presence of bone lesions, their degree of severity, to monitor MM bone disease and to assess effectiveness of anti-myeloma treatment.
  
  
  METHODS
  Serum samples and clinical data from 123 patients with newly diagnosed MM were collected at Riga East Clinical University Hospital (Riga, Latvia) from June 2014 to June 2016. Bone lesions detected by radiography, CT scans, MRI, and PET/CT were divided into degrees from 0 to 3 (0 - no bone involvement, 1 - ≤ 3 bone lesions, 2 - ≥ 3 bone lesions, 3 - fracture). Staging was performed applying Durie/Salmon (DS) and International Staging System classifications. Progressive disease was defined as development of one or more new bone lesions. The levels of bone metabolic markers β-isomerized C-terminal telopeptide of collagen type I (β-CTX) and bone-specific alkaline phosphatase (bALP) were monitored regularly in the year.
  
  
  RESULTS
  Bone lesions were found in 86 (69%) patients. From these 6 (4%) patients had 1st degree, 11 (9%) had 2nd degree and 69 (56%) had 3rd degree bone lesions. Level of the bone resorption marker β-CTX in the control group was 0.41 ng/ml, which is lower than in MM patients (p < 0.001). Spearman correlation coefficient analysis found a positive and statistically significant correlation (rs = 0.51, p < 0.001) between bone lesions degree and β-CTX levels. Mean β-CTX for patients without bone lesions was 0.72 ng/ml (SD = 0.64), but for patients with 3rd degree bone lesions it was 1.34 ng/ml (SD = 0.65) difference being 38% (p < 0.001). In patients who responded to therapy after 6 months of treatment reduction of β-CTX was found compared to baseline values (M = -0.65). In contrast, in patients who did not respond to therapy, there was a statistically significant (p < 0.001) increase in β-CTX values after six months of treatment compared to baseline values (M = 0.42). Exact cutoff value of β-CTX is 0.79. When analyzing mean bALP, no significant difference between MM patients and control group was found. ANOVA statistical analysis showed no statistically significant differences in bALP levels at different degrees of bone lesions (p = 0.95) in MM patients. Analysis of bALP suitability as MM diagnostic marker using receiver operating characteristics curve showed that bALP is not applicable for clinical diagnosis of MM (AUC 0.5, p > 0.05). However, β-CTX was found to be an excellent diagnostic marker for MM (AUC 0.91; 95% confidence interval, 0.88-0.94; p < 0.001).
  
  
  CONCLUSIONS
  Patients with MM and bone lesions have increased value of bone resorption marker β-CTX. There is a correlation between bone resorption marker and degree of bone lesions. Changes in β-CTX levels may be used to monitor the effectiveness of myeloma treatment.
authors.affiliation: Chemotherapy and Haematology Clinic, Riga East Clinical University Hospital, Riga LV 1079, Latvia.
authors.forename: D
authors.initials: D
authors.lastname: Auzina
authors.affiliation: Department of Physics, Riga Stradins University, Riga LV 1079, Latvia.
authors.forename: R
authors.initials: R
authors.lastname: Erts
authors.affiliation: Department of Internal Diseases, Riga Stradins University, Riga LV 1007, Latvia.
authors.forename: S
authors.initials: S
authors.lastname: Lejniece
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D006801:Humans; D007844:Latvia; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D010455:Peptides / Q000378:metabolism; D011379:Prognosis; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase