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Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation.

ABSTRACT: Complex biological pathways including angiogenesis, invasion, osteoclastic activation and bone matrix degradation are involved in the formation of bone metastasis (BM). The aim of our study was to investigate the cross-sectional and longitudinal associations of a panel of 12 serum biochemical markers reflecting biological pathways underlying BM development. In a cross-sectional study, we investigated 29 patients with primary breast carcinoma without BM (BC/BM-), 28 patients with breast carcinoma and BM (BC/BM+) and 15 healthy women. In longitudinal analyses, we investigated 34 patients for whom serum was obtained a two different time points: at the time of primary BC diagnosis and after a median time of 3 years. During this follow-up, 15 patients developed BM, whereas the other 19 remained free of BM. In patients who developed BM, the second samples were obtained before BM was documented by bone scan. The cross-sectional analyses have shown all biochemical markers to be significantly elevated in patients with BM, when compared to the patients without BM and healthy controls, except TGFbeta1 that was significantly decreased. Multivariable analyses showed that only the bone resorption markers TRACP 5b, CTX and ICTP, and the marker of angiogenesis VEGF were independently associated with BM. Those markers correctly distinguished 85% of BC patients with or without BM from normal individuals. Longitudinal analyses showed that patients with primary BC who developed BM during follow-up had higher levels of TRACP5b (+95%, P=0.08) at the time of primary diagnosis, those patients had also a higher increases of ICTP (P=0.006), MMP-7 (P=0.004) and TIMP-1 (P=0.017) during follow-up than patients who did not progress toward bone metastasis. This study provides evidence of increase and interrelationship of circulating markers of angiogenesis, invasion and bone resorption in patients with BC with and without BM. Markers of bone resorption have the highest independent diagnostic value for detecting and potentially predicting BM in breast carcinoma patients.

SUBMITTER: Voorzanger-Rousselot N

PROVIDER: S-EPMC2360666 | biostudies-other | 2006 Aug

REPOSITORIES: biostudies-other

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Project description:ObjectiveTo determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA).MethodsWe analyzed data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Bone marrow lesions (BMLs), osteophytes, and subchondral bone area (mm2 ) and shape (position on 3-D vector) were assessed on magnetic resonance images, and bone trabecular integrity (BTI) was assessed on radiographs. Serum and urinary markers (serum C-terminal crosslinked telopeptide of type I collagen [CTX-I], serum crosslinked N-telopeptide of type I collagen [NTX-I], urinary NTX-I, urinary C-terminal crosslinked telopeptide of type II collagen [CTX-II], and urinary CTX-Iα and CTX-Iβ) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates.ResultsAt baseline, most biochemical markers were associated with BMLs, with C statistics for the presence/absence of any BML ranging from 0.675 to 0.688. At baseline, urinary CTX-II was the marker most consistently associated with BMLs (with odds of having ≥5 subregions affected compared to no BML increasing by 1.92-fold [95% confidence interval (95% CI) 1.25, 2.96] per 1 SD of urinary CTX-II), large osteophytes (odds ratio 1.39 [95% CI 1.10, 1.77]), bone area and shape (highest partial R2 = 0.032), and changes in bone shape over 24 months (partial R2 range 0.008 to 0.024). Overall, biochemical markers were not predictive of changes in BMLs or osteophytes. Serum NTX-I was inversely associated with BTI of the vertical trabeculae (quadratic slope) in all analyses (highest partial R2 = 0.028).ConclusionWe found multiple significant associations, albeit mostly weak ones. The role of systemic biochemical markers as predictors of individual bone anatomic features of single knees is limited based on our findings.

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Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation.

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