Value Of Bone Resorption Metabolic Markers In The Diagnosis And Evaluation Of Bone Metastases In Patients With Malignant Carcinoma

PARTⅠDiagnostic value of bone resorption metabolic markers in the diagnosis of bone metastases in patients with malignant carcinomaObjective To evaluate the usefulness of new bone resorption metabolic markers, such as urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), serum pyridinoline cross-linked C-telopeptides of Type I collagen, in the assessment of bone metastases in patients with malignant carcinoma.Methods The urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx) and serum pyridinoline cross-linked C-telopeptides of Type I collagen (ICTP) were measured by ELISA in 77 malignant carcinoma patients (38 lung carcinoma,35 breast cancer, 1 tonsil cancer, 3 nasopharyngeal carcinoma, of whom 40 patients had bone metastases and 37 patients did not ) .Results Levels of all bone markers in patients with bone metastasis were significantly higher than in patients without bone metastasis (P <0.01). A higher and significant correlation was seen between urinary NTx and serum ICTP (r = 0. 88, P < 0. 05). Using the threshold of 65 nM BCE/ mM Cr for urinary NTx, accuracy, sensitivity, and specificity were 83.2%,82.5 %,83.8% (P < 0. 01), respectively. Using the threshold of 4.5μg/l for serum ICTP, accuracy, sensitivity, and specificity were 80.6%,87.5%,73%(P < 0. 01), respectively. Strong linear associations were seen between the extent of skeletal infiltration and levels of the different biomarkers (urinary NTx r =0.453,serum ICTP r=0.475, p <0.01), but there were no significant correlation between levels of urinary NTx or serum ICTP and bone pain (urinary NTx r =0.01,serum ICTP r=0.083,p>0.05).Conclusion It is suggested that the measurement of urinary NTx, serum ICTP are worthwhile as markers of bone metastases in patient with malignant carcinoma and this measure were considered very helpful in complementary timely diagnosis of bone metastasis.PARTⅡValue of bone metabolic markers in the evaluation of bone metastases in patients with malignant carcinomaObjective To investigate the usefulness of bone turnover markers as a modality for monitoring bone metastasis with bone metastasis.Methods 100 patients with advanced malignant tumor were consecutively enrolled and World Health Organization response criteria were applied for both bone and extraosseous disease every 3 to 4 months. Urine levels of urinary cross-linked N-telopeptides of Type I collagen(NTx), C-terminal telopeptide (CTX), Pyridinoline (PYD )and Deoxypyridinoline (DPD) were measured at 0,1,3,6 month.Results With bisphosphonates , percent change from levels without therapy decreased by 51.8%(P < 0. 05)for NTx , 68.5% for DPD(P < 0. 05),and bisphosphonates did not influence CTx and PYD。A higher and significant correlation was seen between urinary NTx and bone progression (P<0. 01). With disease progression in bone, mean percent change from baseline levels increased by 48.9% for NTx(P < 0. 01)regardless of bisphosphonate therapy, and was 38%,82.5%,45.6% for CTx,PYD,DPD respectively. NTx had the highest sensitivity , specificity and positive predictive value (88%,88.7%,78.6% respectively) for the diagnoses of bone metastases progression. Extraskeletal disease had no significant effect on bone markers. Strong associations were seen between the skeletal complications and levels of NTx or DPD(RR=2.5,1.8, P <0.05), but there were no significant correlation between skeletal complications and levels of urinary CTx ,PYD , pain or extent of skeletal infiltration(P>0.05).Conclusion Urinary NTx may be a valuable bone biochemical marker to assess response to bisphosphonates therapy and to evaluate disease progression of bone metastases.