Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

Wymenga, L. F. A.; Groenier, Klaas H.; Schuurman, Jaap-Peter; Boomsma, J.H.B.; Elferink, Ronald Oude; Mensink, H. J. A.

doi:10.1046/j.1464-410x.2001.02274.x

Cited by 17 publications

(12 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Osteoblastic bone metastases in prostate cancer appear on plain radiographs as areas of increased density (osteodense lesions) and on bone scans as hot spots of increased bone formation 1. In addition, serum bone alkaline phosphatase levels2, 3 and iliac bone histomorphometry4–6 studies have confirmed that bone formation is increased in the tumor-involved sites. However, although these are osteoblastic lesions, the bone that is produced in response to the tumor cells may be fragile and abnormal.…”

Section: Introductionmentioning

confidence: 91%

Histopathological Assessment of Prostate Cancer Bone Osteoblastic Metastases

et al. 2008

View full text Add to dashboard Cite

Purpose-Many patients with prostate cancer develop bone metastases that appear osteoblastic on radiographs, yet these patients have an elevated risk of fractures. The discrepancy between the radiological and clinical aspects of those events is not well understood. The purpose of this study was to better characterize the histopathology of bone processes in prostate cancer bone metastases.Materials and Methods-Histomorphometry was used to evaluate multi-site bone biopsies in each of 12 patients who died with multiple bone metastases, 7 of whom had received bisphosphonate therapy.Results-Bone histomorphometry revealed a wide spectrum of cancer-induced bone changes in different metastatic sites within individual patients, ranging from a pronounced osteodense to a pronounced osteopenic type. Each metastatic lesion was associated with various amounts of resorption. Decreased bone volume was seen in half of all biopsies. Osteodense lesions were largely composed of undermineralized woven bone, which increases frailty of the new bone. Interestingly, woven bone was produced by alkaline phosphatase spindle-shaped cells arising from the connective stroma surrounding tumor cells. Bone response generally was similar in both bisphosphonate-treated patients and those who did not receive bisphosphonate therapy.Conclusions-Despite the osteoblastic nature of bone metastases in prostate cancer, the osteolytic-osteopenic bone lesions found in each clinically osteoblastic patient may explain the frequent fractures observed in these patients. In addition, the finding that woven bone formed directly from the tumor stroma and not from the adjacent bone surface supports further research into the mechanisms of abnormal bone formation in prostate cancer bone metastases.

show abstract

Section: Introductionmentioning

confidence: 91%

Histopathological Assessment of Prostate Cancer Bone Osteoblastic Metastases

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Type I collagen is the major extracellular matrix component of bone, and there is an extensive body of evidence that type I collagen breakdown products, including NTx, are present at elevated levels in the serum and urine of patients with CaP bone metastases. (1)(2)(3)(47)(48)(49) Increased resorption associated with bone metastases, including CaP bone metastases, is linked to stimulation of osteoclastogenesis through RANKL expression. (8 -10) Augmented NTx levels are generally associated with increased osteoclastic bone resorption activity because of cat K expressed by these cells, yet we observed osteoclasts in samples from only 3/14 patients with advanced CaP bone metastases.…”

Section: Cathepsin K In Prostate Cancermentioning

confidence: 99%

“…Although most CaP bone metastases are considered osteoblastic, based on patterns observed on radiographs, there is evidence that markers of bone resorption are elevated in patients with CaP bone lesions. (1)(2)(3) Detailed studies of bone metastases using histomorphometry have also demonstrated that radiographically sclerotic lesions exhibit both bone formation and resorption. (4 -7) Recently it has been established that various cancers, including breast and prostate, support osteoclastogenesis through expression of the receptor activator of NF-kB ligand (RANKL), (8 -10) providing one possible mechanism to explain the increased bone resorption observed with bone metastases.…”

Section: Introductionmentioning

confidence: 99%

Cathepsin K mRNA and Protein Expression in Prostate Cancer Progression

Brubaker

et al. 2003

Journal of Bone and Mineral Research

159

125

View full text Add to dashboard Cite

Prostate cancer (CaP) is the most commonly diagnosed malignancy in men and is often associated with bone metastases, which cause much of the morbidity associated with CaP. Lesions associated with CaP generally exhibit increased bone formation and resorption. Increased bone resorption may release factors from the extracellular matrix that contribute to tumor growth. Cathepsin K (cat K) is a cysteine protease that exhibits strong degradative activity against the extracellular matrix and is involved in osteoclast-mediated bone destruction. In this study, we analyzed the expression of cat K in CaP cell lines and patient samples. Cat K message was detected in CaP cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and in primary CaP and metastases by in situ hybridization. Immunohistochemistry revealed variable expression of cat K in primary CaP samples, as well as nonosseous metastases, whereas expression in bone metastases was significantly higher than in primary CaP, and normal prostate tissues were negative. Cat K protein was detected in CaP cell lines by Western blotting after immunoprecipitation. Cat K enzymatic activity was also detected in CaP cell lines by a fluorogenic assay and by an assay for degradation of collagen type I. Increased levels of NTx, a marker of bone matrix degradation mediated primarily by cat K, were also detected in sera of patients with CaP bone metastases. We hypothesize that CaP-expressed cat K may contribute to the invasive potential of CaP, while increased expression in bone metastases is consistent with a role in matrix degradation.

show abstract

“… 15 ). In patients with prostate cancer, the combined measurement of PSA and BAP in serum seems to increase the diagnostic sensitivity for bone lesions compared to healthy subjects or patients with benign prostate hyperplasia 16–18 …”

Section: Diagnostic Usementioning

confidence: 99%

“…In patients with prostate cancer, the combined measurement of PSA and BAP in serum seems to increase the diagnostic sensitivity for bone lesions compared to healthy subjects or patients with benign prostate hyperplasia. [16][17][18] In general, serum osteocalcin (OC) levels are more variable compared to other bone formation markers, and in advanced, untreated metastatic bone disease, serum OC levels may be low in the presence of high BAP levels. 19 The reasons for this dissociation are unclear, but possibilities include proteolytic cleavage of OC, changes in gene expression or disturbed osteoid maturation in the presence of active tumour osteopathy.…”

Section: Diagnostic Usementioning

confidence: 99%

The use of molecular markers of bone turnover in the management of patients with metastatic bone disease

Seibel

2007

Clinical Endocrinology

View full text Add to dashboard Cite

SummaryBiochemical markers of bone turnover are widely used in clinical practice. These indices have been shown to be associated with the occurrence, prognosis and therapeutic response of malignant bone lesions. For example, markers of bone resorption are often elevated in patients with established bone metastases and while this may point to a role of these markers in the diagnostic workup of cancer patients, the available evidence does not permit any final conclusions as to the accuracy and validity of the presently used markers in the early diagnosis of bone metastases. Many bone turnover markers appear to respond to antiresorptive and antineoplastic therapies, and recent evidence from prospective trials suggests that the aim of bisphosphonate therapy should be to normalize rates of bone remodelling to optimize therapeutic and prognostic outcomes. However, it remains unknown whether the use of bone markers in the routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. Clearly, bone turnover markers have insufficient diagnostic or prognostic value to be used in isolation; however, the combination of these markers with other diagnostic techniques may improve clinical assessment of patients with bone-seeking cancers. This article reviews the available evidence (as of August 2007) on the clinical use of bone turnover markers in the management of patients with metastatic bone disease.

show abstract

Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

Cited by 17 publications

References 12 publications

Histopathological Assessment of Prostate Cancer Bone Osteoblastic Metastases

Histopathological Assessment of Prostate Cancer Bone Osteoblastic Metastases

Cathepsin K mRNA and Protein Expression in Prostate Cancer Progression

The use of molecular markers of bone turnover in the management of patients with metastatic bone disease

Contact Info

Product

Resources

About