Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension

Berruti, Alfredo; Piovesan, Alessandro; Torta, M.; Raucci, Carlo; Gorzegno, G.; Paccotti, Piero; Dogliotti, Luigi; Angeli, Alberto

doi:10.1038/bjc.1996.298

Cited by 62 publications

(26 citation statements)

References 22 publications

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“…However, while important gains in understanding the role of osteoclastic activity have been made for osteolytic tumors, the importance of osteoclastic activity in the development of prostate cancer skeletal metastatic lesions has received little attention because of their overall osteoblastic radiographic appearance. Yet, despite the radiographic appearance, it is clear from histological evidence that prostate cancer metastases form a heterogeneous mixture of osteolytic and osteoblastic lesions (2,(20)(21)(22)(23). In fact, histomorphometric analysis of metastatic lesions reveals that osteoblastic metastases form on trabecular bone at sites of previous osteoclastic resorption, suggesting that bone resorption is required for subsequent osteoblastic bone formation (2).…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin inhibits prostate cancer–induced osteoclastogenesis and prevents prostate tumor growth in the bone

Zhang¹,

Dai²,

Qi³

et al. 2001

J. Clin. Invest.

423

363

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IntroductionProstate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer death among men in the US. The most common site of prostate cancer metastasis is the bone, with up to 84% of patients demonstrating skeletal metastases (1). While initially thought to be primarily osteoblastic, it is now recognized that prostate cancer skeletal metastases have an extensive bone resorptive component (2, 3) that is caused primarily by osteoclasts (4). This accounts, in part, for the ability of bisphosphonates, which are antiosteoclastogenic agents, to diminish osteolysis, decrease pain, and improve mobility in patients with prostate cancer skeletal metastasis (5). However, the mechanisms through which prostate cancer skeletal metastases induce osteolytic lesions are not defined.The presence of an osteolytic component in prostate cancer skeletal metastases suggests that osteoclastogenesis may play a role in the establishment of these lesions. Recently, the discovery and characterization of a novel cytokine system -the TNF family member, receptor activator of NF-κB ligand (RANKL, also called OPGL, TRANCE, and ODF); its receptor, receptor activator of NF-κB (RANK, also called ODAR); and its decoy receptor, osteoprotegerin (OPG, also called OCIF and TR1) -has established a common mechanism through which osteoclastogenesis is regulated in normal bone (reviewed in ref. 6). RANKL, a transmembrane molecule located on bone marrow stromal cells and osteoblasts, binds to RANK, which is located on the surface of osteoclast precursors. This ligand-receptor interaction activates NF-κB, which stimulates differentiation of osteoclast precursors to osteoclasts. OPG, also produced by osteoblasts/stromal cells, binds to RANKL, sequestering it from binding to RANK, which results in inhibition of osteoclastogenesis. The requirement for RANKL to induce osteoclastogenesis suggests that it may mediate the osteolytic component of prostate cancer skeletal lesions. However, it is currently unknown if prostate cancer uses the Prostate cancer (CaP) forms osteoblastic skeletal metastases with an underlying osteoclastic component. However, the importance of osteoclastogenesis in the development of CaP skeletal lesions is unknown. In the present study, we demonstrate that CaP cells directly induce osteoclastogenesis from osteoclast precursors in the absence of underlying stroma in vitro. CaP cells produced a soluble form of receptor activator of NF-κB ligand (RANKL), which accounted for the CaP-mediated osteoclastogenesis. To evaluate for the importance of osteoclastogenesis on CaP tumor development in vivo, CaP cells were injected both intratibially and subcutaneously in the same mice, followed by administration of the decoy receptor for RANKL, osteoprotegerin (OPG). OPG completely prevented the establishment of mixed osteolytic/osteoblastic tibial tumors, as were observed in vehicle-treated animals, but it had no effect on subcutaneous tumor growth. Consistent with the role of osteoclasts in tumor development, oste...

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Section: Discussionmentioning

confidence: 99%

Osteoprotegerin inhibits prostate cancer–induced osteoclastogenesis and prevents prostate tumor growth in the bone

Zhang¹,

Dai²,

Qi³

et al. 2001

J. Clin. Invest.

423

363

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“…There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).…”

mentioning

confidence: 94%

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Garnero

Buchs

Zekri³

et al. 2000

Br J Cancer

217

128

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Prostate cancer is the most common malignancy in elderly men and is often complicated by osteosclerotic metastases. Bone scintigraphy is commonly used to assess the extent of bone metastases; its use is limited in monitoring of treatment efficacy because it is an expensive, time-consuming technique that does not reflect the rapid skeletal response to therapy (Coleman, 1998). The bone scan flare response following successful therapy also reduces the value of bone scanning in the early monitoring of treatment in prostate cancer (Pollen et al, 1984). The serum level of prostatespecific antigen is the most sensitive index of disease progression in most but not all patients, but does not reflect the effects of palliative treatments such as bisphosphonates for bone metastases in patients that escape from antihormonal therapy.The marked increase of osteoblastic activity in patients with osteosclerotic metastases is reflected by increased levels of serum total and bone-specific alkaline phosphatase (Pecherstorfer et al, 1995;Lorente et al, 1996). There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).In this study we assessed the level of bone resorption in patients with osteosclerotic metastases from prostate cancer before and after bisphosphonate treatment by using new sensitive and specific biochemical markers of bone resorption including a serum assay for type I collagen C-telopeptide breakdown products; and values were compared to those of bone formation markers. PATIENTS AND METHODSForty-eight patients with carcinoma of the prostate (age 71.7 ± 9.6 years, mean ± 1 s.d.) and nine with benign prostatic hyperplasia (BHP) (age 69.8 ± 4.2 years) were enrolled. All patients with cancer had a prostatic biopsy and tissue diagnosis of adenocarcinoma. Bone involvement and its extent was evaluated by bone scintigraphy using Technetium-99m labelled methylene bisphosphonate. When bone metastases were suspected, confirmation was obtained with standard radiographs, computerized tomography (CT) and/or magnetic resonance imaging. The metastatic load in Summary Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to tha...

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“…Показано, что уровень СТХ в моче отражает ин-тенсивность остеолиза и определяет прогноз у боль-ных РМЖ с метастазами в костях [60]. Нами проана-лизирована взаимосвязь результатов определения СТХ в сыворотке крови больных РМЖ с клиническими проявлениями метастазов в костях (табл.…”

Section: маркеры резорбции костной тканиunclassified

Biochemical markers of bone metastasis

Любимова¹,

Кушлинский²

2015

Usp. mol. onkol

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Bone metastasis is one of the most frequent and dangerous complications of malignant tumors. The last years , achievements in the study of bone remodeling mechanisms promoted the search of sensitive and specific criteria reflecting the intensity of osteolysis and osteosynthesis in bone metastatic lesions. The most informative and clinically valid biochemical markers of bone formation and resorption are characterized in this review. The data on their possible implications in diagnostics, monitoring and prognosis of skeletal lesions by various malignant tumors are presented. The attention to biochemical markers of bone remodeling as noninvasive methods for oncologic patients examination is gradually increasing with adoption of modern laboratory technologies to clinical practice. The last years , publications suggest the possibility of their use both for monitoring, prognosis and early diagnostics of bone metastasis. We present the results of our own investigation of serum C-telopeptide of type I collagen (СТX) as bone resorption marker and bone-specific alkaline phosphatase (BAP) as formation marker in238 breast cancer patients using ELISA methods. The elevation of studied biochemical parameters in breast cancer patients was significantly associated with the extent of skeletal metastases (р < 0.02-0.00001), pathological fractures (р < 0.005-0.0001) and the severity of pain (р < 0.01-0.00002 Введение Метастазирование в кости -частое и опасное осложнение злокачественных опухолей, которое сни-жает продолжительность и качество жизни пациентов, вызывая сильные боли, патологические переломы, гиперкальциемию и компрессию спинного мозга. Наи-более часто в кости метастазирует рак простаты (54-85 %), рак молочной железы (РМЖ; 47-85 %), рак

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Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension

Cited by 62 publications

References 22 publications

Osteoprotegerin inhibits prostate cancer–induced osteoclastogenesis and prevents prostate tumor growth in the bone

Osteoprotegerin inhibits prostate cancer–induced osteoclastogenesis and prevents prostate tumor growth in the bone

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Biochemical markers of bone metastasis

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