Markers of bone turnover in bone metastases

Fontana, A; Delmas, Pierre D.

doi:10.1002/1097-0142(20000615)88:12+<2952::aid-cncr11>3.0.co;2-m

Cited by 96 publications

(60 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The markers of bone turnover, which include enzymes predominantly expressed by the osteoblasts, such as bone alkaline phosphatase (bone ALP), and osteoclasts -such as the tartrate resistant acid phosphatase, (TRACP) -or bone matrix synthesis and degradation products (Fontana et al, 1999) have demonstrated increased serum and urine levels in patients with bone metastases (Demers et al, 2000). Our previous study has shown that bone matrix degradation markers especially the type I collagen Ctelopeptides fragments CTX and ICTP, which reflect cathepsin Kand MMP-mediated type I collagen degradation, respectively, could be useful in monitoring bone metastasis (Garnero et al, 2003a).…”

mentioning

confidence: 99%

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

Voorzanger-Rousselot¹,

Juillet²,

Mareau³

et al. 2006

Br J Cancer

View full text Add to dashboard Cite

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/BMÀ), 28 patients with breast carcinoma and BM (BC/ BM þ ) 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 TGFb1 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 ( þ 95%, P ¼ 0.08) at the time of primary diagnosis, those patients had also a higher increases of ICTP (P ¼ 0.006), MMP-7 (P ¼ 0.004) and TIMP-1 (P ¼ 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. Bone is one of the most common sites of metastasis for certain types of tumours, especially prostate, breast and lung carcinoma (Mundy, 2002). Breast cancer progression to bone is a defining feature of a highly malignant tumour and the major cause of cancer-treatment failure. Early detection of bone metastasis is critical for clinical management and accurate staging of tumours. Currently there is no a simple way to reliably detect and predict which patients will develop bone metastasis. The detection of bone metastases relies on imaging technology, but novel approaches based on biomarker assessments are under intense investigation. Increasing body of data suggests that metastatic dissemination is site specific (Horak and Steeg, 2005) and that distinct molecular factors regulate bone metastasis formation (Yin et al, 2005). A multifactorial and multistep process of bone metastasis formation involves several biological mechanisms including angiogenesis, invasion through...

show abstract

mentioning

confidence: 99%

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

Voorzanger-Rousselot¹,

Juillet²,

Mareau³

et al. 2006

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Despite the high incidence and serious consequences of skeletal metastasis of prostate cancer, the mechanisms underlying this osteotropism are poorly understood. However, it is clear that bone-specific matrix proteins and their receptors on the surface of prostate cancer cells play a pivotal role in the process (1)(2)(3). Recent analysis of bone extracts has revealed that a key factor that mediates prostate cancer cell invasion is the protein osteonectin or SPARC 1 (secreted protein, acidic and rich in cysteine) (4).…”

mentioning

confidence: 99%

Molecular Pathway for Cancer Metastasis to Bone

Chen

Narizhneva

et al. 2003

Journal of Biological Chemistry

138

130

View full text Add to dashboard Cite

The molecular mechanism leading to the cancer metastasis to bone is poorly understood but yet determines prognosis and therapy. Here, we define a new molecular pathway that may account for the extraordinarily high osteotropism of prostate cancer. By using SPARC (secreted protein, acidic and rich in cysteine)-deficient mice and recombinant SPARC, we demonstrated that SPARC selectively supports the migration of highly metastatic relative to less metastatic prostate cancer cell lines to bone. If prostate cancer is locally confined, the 5-year survival rate is nearly 100%; however, if the cancer metastasizes to distant sites, the 5-year survival rate is only 31%. Bone is by far (80 -85%) the primary site of prostate cancer metastasis. Despite the high incidence and serious consequences of skeletal metastasis of prostate cancer, the mechanisms underlying this osteotropism are poorly understood. However, it is clear that bone-specific matrix proteins and their receptors on the surface of prostate cancer cells play a pivotal role in the process (1-3). Recent analysis of bone extracts has revealed that a key factor that mediates prostate cancer cell invasion is the protein osteonectin or SPARC 1 (secreted protein, acidic and rich in cys-

show abstract

“…It has been suggested that the detection of LP in the serum or urine may be a helpful marker in establishing and possibly quantifying bone matrix resorption (Body and Delmas, 1992;Miyamoto et al, 1994;Vinholes et al, 1996;Papatheofanis, 1997;Tamada et al, 2001). The measurement of HP and, in particular, LP has been shown to be valuable in detecting the presence and/or extent of bony metastases in patients with multiple myeloma, carcinoma of the breast, lung, prostate gland, kidney, throat and digestive tract (Takeuchi et al, 1996;Papatheofanis, 1997;Walne et al, 1997;Yoshida et al, 1997;Coleman et al, 1999;Marttunen et al, 1999;Tamura et al, 1999;Woitge et al, 1999Woitge et al, , 2001Demers et al, 2000;Fontana and Delmas, 2000;Liubimova et al, 2000;Izumi et al, 2001;Tamada et al, 2001).…”

mentioning

confidence: 99%

Collagen crosslink excretion and staging of oral cancer

et al. 2003

View full text Add to dashboard Cite

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n ¼ 17); group 2: patients with confirmed OSCC (n ¼ 12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n ¼ 13); group 4: patients without clinical evidence of disease (n ¼ 74). The range and upper limit of normal values (HP max and LP max ) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1 -4 (Po0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

show abstract

Markers of bone turnover in bone metastases

Cited by 96 publications

References 57 publications

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

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

Molecular Pathway for Cancer Metastasis to Bone

Collagen crosslink excretion and staging of oral cancer

Contact Info

Product

Resources

About