title: Comparison of bone scintigraphy with bone markers in the diagnosis of bone metastasis in lung carcinoma patients.
abstract: This study was designed to evaluate the utility of the bone markers total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), aminoterminal propeptide of type I collagen (PINP), carboxyterminal propeptide of type I collagen (PICP), pyridinoline crosslinks (PYD), deoxypyridinoline crosslinks (DPD), cross-linked carboxyterminal telopeptide of type I collagen (ICTP), cross-linked carboxyterminal telopeptide of type I collagen (CTx, beta-CrossLaps) and tartrate-resistant acid phosphatase 5b (TRAP 5b) in comparison with bone scintigraphy for the diagnosis of bone metastasis in lung carcinoma patients. The study population consisted of 49 patients with bone metastasis confirmed by plain radiography and/or computed tomography, 89 patients without bone metastasis, 12 patients with benign lung diseases and 18 healthy persons. All patients were of male gender. The bone markers were measured using commercially available tests. Serum and urine were collected from fasting patients at the time of bone scan between 7.00 and 8.00 a.m. The sensitivity of bone scintigraphy was 100%, its specificity 76.4%, resulting in a diagnostic efficiency of 84.8%. The positive predictive value was calculated to be 70% and the negative one to be 100%. The concentrations of the bone markers TAP, BAP, PINP, PYD, DPD and ICTP were significantly higher in patients with bone metastasis than in those without bone metastasis (p<0.01). The levels of PICP and CTx only tended to be higher in the patients with bone metastasis compared to those without bone metastasis. There was no significant difference in the TRAP 5b levels between the two groups. There was also no difference in the marker levels between osteoblastic, osteolytic and mixed osteoblastic-osteolytic lesions. Contrary to BAP, PICP, CTx and TRAP 5b, the markers TAP, PINP, PYD, DPD and ICTP were found to be higher (p<0.01-0.05) in patients with bone metastasis than in patients with benign lung diseases. In addition, PYD, DPD and ICTP differentiated patients with benign lung diseases from the healthy controls. Based on cut-off values that correspond to 95% specificity in the group of healthy persons, the sensitivity of the marker assays were as follows (specificity in brackets): TAP 33.3% (97.5%), BAP 22% (100%), PINP 18.4% (97.5%), PICP 2.1% (95.2%), PYD 91.8% (24.1%), DPD 83.7% (34.5%), ICTP 75.5% (44.6%), CTx 45.8% (77.5%) and TRAP 5b 14% (84%). The corresponding data for the diagnostic efficiency were as follows: TAP 73.6%, BAP 77.1%, PINP 67.7%, PICP 61.1%, PYD 48.5%, DPD 55.2%, ICTP 56.1%, CTx 65.6% and TRAP 5b 58.7%, respectively. The positive predictive values ranged from 20% (PICP) to 100% (BAP) and the negative values from 62.7% (PICP) to 84% (PYD). In the ROC analysis, TAP, followed by RAP, PINP and PYD, showed the best performance. The levels of TAP, BAP, PINP, PYD, DPD and ICTP were found to be higher in the patients with bone metastasis compared to those with metastastic lesions in other sites (p<0.01, except for ICTP having a p value of < 0.05). The levels of TAP, BAP, PYD, DPD and ICTP increased significantly with the number of metastases. There was also a steady increase in T scores of the markers PINP, PYD, DPD and ICTP with the extent of the metastatic bone disease. It is concluded that the currently available bone markers cannot replace bone scintigraphy, either for screening or in the diagnosis of bone metastasis, in lung carcinoma patients. However, a panel consisting of TAP, BAP, PINP, PYD, DPD and ICTP may be of some value as an adjunct tool to bone scintigraphy for this purpose.
authors.affiliation: Thoraxklinik Heidelberg gGmbH, University of Heidelberg, Heidelberg, Germany. prof.ebert@t-online.de
authors.forename: W
authors.initials: W
authors.lastname: Ebert
authors.forename: Th
authors.initials: T
authors.lastname: Muley
authors.forename: K P
authors.initials: KP
authors.lastname: Herb
authors.forename: H
authors.initials: H
authors.lastname: Schmidt-Gayk
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism / Q000556:secondary*; D003094:Collagen / Q000032:analysis; D024042:Collagen Type I; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides / Q000032:analysis; D011347:Procollagen / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D007527:Isoenzymes; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D003094:Collagen; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase