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The bone resorption biomarker sNTx has been previously shown to add value as an aid in the diagnosis of bone metastasis in patients with lung cancer. The objective of this prospective study was to determine whether periodic sNTx measurements could lead to early diagnosis of bone metastasis in patients with lung cancer.Patients with newly diagnosed organ-confined lung cancer were enrolled. sNTx values were determined once each month using the OSTEOMARKTM serum NTx assay (Alere Medical). The presence or absence of bone metastasis was determined by monthly physical examination and by bone scintigraphy every 3 months for 12 months. All patients were required to provide written informed consent.Forty patients were enrolled between June and December 2010. One patient withdrew early and was excluded from analysis. The mean ± 1 SD baseline level of sNTx was 17.5 ± 4.4 nM BCE/L. Five patients developed bone metastasis (as characterized by bone scintigraphy) during the study period. The level of sNTx in subjects with bone metastasis was slightly increased (21.6 ± 3.2 nM BCE/L), however, in these patients, there was no statistically significant difference between sNTx values at baseline (18.2 ± 4.2 nM BCE/L) and when metastasis was diagnosed. (P = 0.176). When a cut-off value of sNTx was set to 22.0 nM BCE/L, the sensitivity and the specificity of detection of bone metastasis were 80.0% and 41.2%, respectively. Using this cut-off, the elevation of sNTx could predict bone metastasis at least one month before diagnosis by bone scintigraphy in all 5 patients, however, the specificity was relatively low for clinical implementation. Additionally, the sensitivity and the specificity of early detection of systematic spread of disease (including bone metastasis) were 70.6% and 45.5%, respectively.Periodic determination of sNTx in patients with organ confined lung cancer did not provide sufficient specificity for it to be used for the early diagnosis of bone metastasis or disease progression.