PURPOSE: To assess the efficacy of bone turnover markers monitoring for prediction of overall survival and event-free survival in patients with multiple myeloma. To determine the value of initial measurement for differential diagnosis and evaluation of myeloma stage and activity.

METHODS AND RESULTS: We evaluated 79 consecutive, previously untreated patients with myeloma and 24 with monoclonal gammopathy of undetermined significance. Urine excretion rates of pyridinoline (PYR) and deoxypyridinoline (DPYR) as markers of bone resorption and serum osteocalcin (OC) as marker of bone formation were measured at diagnosis and further repeatedly during the course of disease. High-performance liquid chromatography (HPLC) was used to measure urinary excretion rates of PYR and DPYR, serum OC levels was analysed using RIA method. Significant correlation was found between PYR and DPYR levels (p < 0.001) and between DPYR and OC (p < 0.05). Significantly higher urine PYR and DPYR (p < 0.001 and p < 0.01, respectively), but not serum OC, were found in myeloma comparing MGUS. In patients with MM PYR and DPYR levels were significantly higher in stage III vs. I and II (p < 0.01), the correlation with disease activity was not found. The grade of bone involvement according to RTG (osteolysis, osteoporosis, absence of bone lesions) was not reliable as a prognostic factor in our study. Univariate overall survival analysis showed prognostic significance for initial PYR (p < 0.05) but not for DPYR and/or OC. Rapid decrease of PYR (after 1 month of chemotherapy) was associated with the shortest median survival (608 days), however, significant difference was observed only comparing the patients in which PYR decreased 12 months after start of chemotherapy. In the univariate analysis increase of DPYR was the only variable significant for event-free survival (p < 0.05), increase of PYR tend to be significant (p < 0.1).

CONCLUSIONS: We confirmed possible contribution of pyridinium cross-links for differential diagnosis of MM and MGUS and the correlation with advanced stage of MM. Initial measurement of PYR and monitoring of both PYR and DPYR during the course of myeloma could be helpful for prediction of overall survival and event-free survival. According to our experience OC is not useful for diagnosis, assessment of disease stage and activity and prediction of survival of patients with MM.

Keywords: Adult; Aged; Aged, 80 and over; Amino Acids /urine/; Biomarkers /analysis/; Bone Remodeling; Humans; Middle Aged; Multiple Myeloma /mortality/; Osteocalcin /blood/; Paraproteinemias /pathology/