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    • Since BM impairs the balance between bone formation and

    2019-05-17

    Since BM impairs the balance between bone formation and bone resorption, altered bone remodeling activities can be assessed directly by measuring the components of affected bone cells or indirectly by analyzing metabolic products released from the bone matrix by changed rates of bone formation or resorption. Numerous new analytical tools for bone turnover markers (BTMs) have improved the diagnosis of BM. These BTMs have been recommended as helpful tools for assessing BM [6]. Collectively, there seem to be a diversity of findings depending on cancer type and the type of BTMs used. Previous researches had explored the applications of BTMs in NSCLC patients [7–19], nevertheless, as to the optimal markers and their proper application in BM screening, there hasn\'t been a consistent agreement, which greatly hampered the BTMs usage in clinical practice.
    Materials and methods
    Results
    Discussion Previous reports evaluating BTMs for the detection of BM in patients with malignant diseases have concluded that urinary N-telopeptide of type I collagen (NTx) is the most useful BTMs [6,11,23]. The usefulness of uNTx to diagnose early BM has been reported in several studies [24–26]. Analyses were performed in both serum and urine, but consistent results were not always described. The pre-analytic variability of BTMs, their different stability in vitro especially in urine and use of assays with different pteryxin recognizing different epitopes may explain many of the discrepant results [28–31]. Seibel [32] indicated serum as the preferred matrix for measurement. He reported the need to measure formation markers (BAP, N-MID, PINP) in serum. Among resorption markers, collagen-derived products can be measured in serum and urine (β-CTx, NTx). In our opinion, the preferred sample matrix is serum. The use of a single serum for the measure of multiple markers is desirable to simplify pre-analytical and analytical procedures. As commercial assays for measuring BTMs in serum are available, we evaluated the diagnostic value of BTMs in clinical use in detecting BM in NSCLC patients, BALP, PINP and OC, bone formation markers, and CTX, bone resorption markers, which can all be measured in automatically in on sample are assessed. To avoid these discrepancies as far as possible, we measured BTMs exclusively in serum collected during a defined time period, between 7:00 and 9:00A.M. The diagnosis of BM in NSCLC patients relies predominantly on imaging techniques. Although these techniques provide useful diagnostic tools, their use for early diagnosis or close monitoring of patients is not without limitations. BTMs as indicators for BM in NSCLC patients have been studied, but there are no clear recommendations which markers or marker combinations should be used [7–19]. Kong [22] found that the increased CTX level had the specificity and sensitivity of 65.6% and 68.8%, respectively, in the diagnosis of BM in NSCLC patients, and they speculated that CTX could be used to screen the BM of NSCLC. Ebert [7] found the concentrations of the bone markers BALP, PINP were significantly higher in patients with BM than in those without BM. In our attempt to document the predictive value of these BTMs in NSCLC patients, we studied a cohort of 414 cancer patients with or without radiographic evidence of BM. We measured the levels of several BTMs in NSCLC patients to assess which BTMs, if any, best reflected the presence of BM. Compared with previous literatures [12,13,15,16,34], we chose NSCLC patients with no evidence of BM as the control group instead of healthy people. It is known that the balance of bone metabolism is regulated through the action of various systemic hormones and local mediators. We assumed that the formation of tumor in the body, even without evidence of BM, may influence the concentration of those hormones and mediators and result in up-regulation of BTMs. Our results showed the levels of BALP, PINP, N-MID, and β-CTX in the BM group were significantly higher than those in without BM groups. The sample size is considerable and the study provides a valid confirmation of previous reports in smaller studies.