Biochemical markers of bone disease in asymptomatic early stage multiple myeloma. A study on their role in identifying high risk patients

Background and Objectives. Skeletal involvement is typical of multiple myeloma (MM) and its occurrence increases with the progression of the disease. We performed a study to evaluate the clinical importance of osteocalcin (bone gla-protein, BGP) and bone alkaline phosphatase (b-AP) as indices of osteoblastic activity, and deoxypyridoline (DPD) as a marker of bone resorption. Design and Methods. Fifty-two MM patients, 39 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 normal controls entered the study. Of the 52 MM patients, 10 showed lytic lesions at standard X-rays and 42 did not; 21 were untreated and 31 had been treated with chemotherapy (combined with bisphophonates in 15). Of these last, 12 had progressive disease and 19 were in plateau phase. Results. DPD levels were higher in MM patients than in patients with MGUS or healthy controls (p=0.0001 and p=0.0008, respectively). No statistical differences were seen between patients with MGUS and healthy controls. BGP serum levels were significantly lower in MM patients than in MGUS patients (p=0.001) or healthy controls (p=0.001). b-AP was significantly higher in MGUS patients than in MM patients (p=0.04). Biochemical parameters were analyzed in a continuous fashion and after dichotomization into low and high values with respect to normal ones. Abnormal high values of DPD showed statistically significant correlations with presence of osteolysis (p=0.008), advanced stage (p=0.03) and abnormal β2-microglobulin (β2M) values (p=0.03), while DPD as a continuous variable correlated significantly only with the presence of osteolysis (p=0.02). In contrast, neither BGP nor b-AP showed statistical correlations with the presence of lytic lesions, or with other clinical or laboratory parameters. In 15 patients followed with serial controls, modifications of DPD levels reflected bone disease status well. Of the 42 patients without radiologic evidence of skeletal lesions, 15 had abnormal DPD values. Spinal magnetic resonance imaging (MRI) showed initial lytic lesions in 10 of them. Interpretation and Conclusions. Biochemical markers of bone metabolism are useful in evaluating and monitoring skeletal involvement in MM patients. They may help clinicians to identify: 1) from among patients without radiologic evidence of lytic lesions, those who deserve more accurate radiologic examinations (namely MRI); 2) from among asymptomatic patients, and in association with spinal MRI, those patients at higher risk of progression who might benefit from early treatment.