Differential patterns of bone turnover in relation to bone pain and disease extent in bone in cancer patients with skeletal metastases

Background: The alteration of the bone microenvironment as a consequence of skeletal metastases is poorly understood. The aim of this study was to sea rch for patterns of bone markers in relation to primary tumor type, bone pa in, and number of sites involved in patients with bone metastases, Methods: We studied 323 patients with bone metastases from various primary malignancies. We sequentially measured the serum concentrations of bone alk aline phosphatase [by an electrophoretic technique (BALP)] carboxy-terminal telopeptide of type I collagen (ICTP), calcium (CaS), intact parathyroid h ormone (PTH), and the fasting urinary excretion of calcium (Ca:Cr). Immunor adiometric serum bone alkaline phosphatase (I-BALP) and urinary excretion o f deoxypyridinoline (DPYD) were also assessed-in the 175 cases; Data were a nalyzed as a function of bone pain (assessed by a validated pain questionna ire), the number of radiographically confirmed sites of bone involvement, a nd the most frequent primary tumor types: breast cancer (BC; 124 patients), prostate cancer (PC; 90 patients), and non-small cell lung cancer (LC; 49 patients). Results: Serum BALP and I-BALP correlated with the number of radiologically identified blastic bone lesions. BALP and I-BALP were more frequently incr eased in PC (72% for both measurements) than in BC (50% and 60%, respective ly) or LC (3% and 5%, respectively; P <0.001 for BALP and P = 0.001 for I-B ALP). ICTP and DPYD values did not differ among PC, BC, and LC, but they di d show a direct relationship with the disease extent in bone (P <0.001). Ca S and Ca:Cr did not vary significantly according to the bone tumor burden. Bone pain directly correlated with ICTP (P <0.001), DPYD (P = 0.002), CaS ( P <0.002), and Ca:Cr (P = 0.0010, whereas the relationship was inverse for serum PTH CP = 0.002). When patients were stratified according to the prima ry tumor, ICTP correlated with the bone pain in all subsets (P <0.005, <0.0 05, and <0.001 for BC, PC, and LC, respectively), as did CaS and Ca:Cr in L C patients (P = 0.01 and 0.02, respectively) but not in PC and BC patients. Conclusions: The patterns of bone turnover markers differ among the primary tumor types. Both resorption and formation markers reflect the number of r adiographically identified sites of bone metastases, whereas resorption mar kers and serum calcium but not formation markers correlate with bone pain. (C) 1999 American Association for Clinical Chemistry.