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      Usefulness of Bone Metabolic Markers in the Diagnosis of Bone Metastasis from Lung Cancer

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          Abstract

          Bone metastasis is common in lung cancer patient and the diagnosis of bone metastasis is usually made by using imaging techniques, especially bone scintigraphy. However, the diagnostic yield from bone scintigraphy is limited. The aim of this study is to assess the clinical usefulness of urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), urinary deoxypyridinoline (DPD), and serum alkaline phosphatase (ALP) in the assessment of bone metastasis in patients with lung cancer. Urinary NTx, DPD, and serum ALP were measured in 151 lung cancer patients (33 with and 118 without bone metastasis). Lung cancer patients with bone metastasis had a higher urinary excretion of NTx and DPD, and a higher serum ALP than those without bone metastasis. NTx had a better receiver operating characteristic (ROC) curve than DPD and ALP, since the areas under the ROC curve were 0.82, 0.79, and 0.71, respectively. Although correlation coefficients among NTx, DPD and ALP were significantly positive ( p < 0.005), the strongest relationship was appeared between NTx and DPD (R=0.616). In conclusion, our results showed the utility of the new bone markers in detecting bone metastasis and suggested that measurement of urinary NTx was valid diagnostic method of bone metastasis from lung cancer.

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          Most cited references16

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          A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine.

          Peptides of low molecular weight that contain pyridinoline cross-links were isolated from adolescent human urine. A fraction was selected that was enriched in the N-telopeptide-to-helix intermolecular cross-linking domain of bone type I collagen. Mouse monoclonal antibodies were generated against these urinary peptides conjugated to a carrier protein as immunogen. A high-affinity antibody was identified that specifically bound to the trivalent peptides derived from the N-telopeptide-to-helix pyridinoline cross-linking site in type I collagen of human bone. This was confirmed by the direct isolation from human bone collagen of similar fragments recognized selectively by the antibody. A sensitive inhibition ELISA was established on microtiter plates that could quantify the bone-derived peptides in human urine. The assay, which can be run directly on untreated urine, was thoroughly tested against samples from normal subjects and from patients with metabolic bone disease. For example, strong correlations with urinary hydroxyproline and total pyridinoline cross-links were found in patients with Paget's disease of bone. The method shows considerable promise as a rapid and specific index of human bone resorption rates, with greatly improved specificity and convenience over total pyridinoline analysis. Potential applications include the study of normal metabolism, the diagnosis and monitoring of bone disease, and evaluating the effectiveness of antiresorption therapies.
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            Presenting conditions of 1539 population-based lung cancer patients by cell type and stage in New Hampshire and Vermont.

            The authors identified all newly diagnosed lung cancer cases in New Hampshire and Vermont for the period 1973 through 1976 and abstracted clinical data on presenting symptoms and findings from their hospital records. Microscopy slides were also reviewed, when possible, to confirm cell type. The most frequent presenting symptoms were weight loss (46%) and cough (45%). Other common symptoms were dyspnea (37%), weakness (34%), chest pain (27%), and hemoptysis (27%). The presence of symptoms and findings was in general related to disease stage but bore little relationship to cell type. These results differ from those of previously reported case series that were based on surgical, radiation therapy, or Veterans Hospital groups, but the current data agree closely with those from another population-based series in Finland.
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              Bone resorption parameters [carboxy-terminal telopeptide of type-I collagen (ICTP), amino-terminal collagen type-I telopeptide (NTx), and deoxypyridinoline (Dpd)] in MGUS and multiple myeloma.

              Skeletal morbidity is a major problem in multiple myeloma. Histomorphometric studies have demonstrated that increased bone resorption can be present even in the absence of radiographic abnormalities. To overcome diagnostic problems in estimating the activity of bone resorption, new laboratory parameters that reflect bone metabolism accurately are urgently needed. We analyzed three parameters of osteoclastic bone destruction, i.e. deoxypyridinoline (Dpd) and amino-terminal collagen type-I telopeptide (NTx) in urine and carboxy-terminal telopeptide of type-I collagen (ICTP) in serum, of 75 patients with multiple myeloma (n = 57) or monoclonal gammopathy of undetermined significance (MGUS, n = 18) by ELISA/RIA techniques. Serum ICTP and urinary Dpd levels increased parallel to the stage of the disease and differed significantly (P < 0.001 for ICTP and P = 0.03 for Dpd) between MGUS, myeloma stage I, and myeloma in stages II and III according to Salmon and Durie. ICTP and Dpd were significantly elevated in patients with multiple myeloma in stage I compared to individuals with MGUS, while no significant difference was found for NTx. In this first study comparing the prognostic relevance of ICTP, NTx, and Dpd in multiple myeloma patients, ICTP was found to be a prognostic factor for overall survival in the Kaplan-Meier analysis (log-rank test: P < 0.03). Urinary NTx showed borderline significance (P = 0.05), and Dpd had no prognostic value in the survival analysis. Our data show that serum ICTP and urinary Dpd levels increase in parallel to advanced disease stages, and gives the first report on a significant difference in the bone resorption parameters ICTP and Dpd between individuals with MGUS and patients with myeloma in stage I. Among the bone resorption parameters studied serum ICTP was found to be the best prognostic factor for survival in multiple myeloma.
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                Author and article information

                Journal
                Yonsei Med J
                YMJ
                Yonsei Medical Journal
                Yonsei University College of Medicine
                0513-5796
                1976-2437
                30 June 2005
                30 June 2005
                : 46
                : 3
                : 388-393
                Affiliations
                [1 ]Department of Internal Medicine, Kwandong University College of Medicine, Koyang, Korea.
                [2 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
                [3 ]The Institute of Chest Diseases, Yonsei University College of Medicine, Seoul, Korea.
                [4 ]Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
                [5 ]Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea.
                Author notes
                Reprint address: requests to Dr. Se Kyu Kim, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-2228-1954, Fax: 82-2-2228-1954, sekyukim@ 123456yumc.yonei.ac.kr
                Article
                10.3349/ymj.2005.46.3.388
                2815816
                15988811
                dd22e06d-0fa2-4b7c-acf9-e226c5f0b052
                Copyright © 2005 The Yonsei University College of Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 November 2004
                : 17 March 2005
                Categories
                Original Article

                Medicine
                lung neoplasms,urinary n-telopeptide of type i collagen,deoxypyridinoline,neoplasm metastasis,bone

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