Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: Diagnostic and prognostic implications

Abstract

Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n ‫؍‬ 39; pN1M0, n ‫؍‬ 34; M1, n ‫؍‬ 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin ( Key words: bone turnover marker; prostate carcinoma; bone metastasis; osteoprotegerin; diagnostic accuracyThe most frequent cancer in men, PCa, is characterized by the occurrence of skeletal metastases in about 65-75% of patients with advanced disease. 1 Bone metastases alter the balance between bone formation and bone resorption by influencing the involved bone cells (osteoblasts and osteoclasts) through local release of cytokines and growth factors. To detect and monitor this metastatic bone involvement, bone scintigraphy is the widely applied standard method. Altered bone remodeling activity can also be assessed either directly by measuring components of the affected bone cells (osteoblasts and osteoclasts) or indirectly by analyzing metabolic products released from the bone matrix following the changed bone formation or resorption. Bone turnover markers that reflect either bone formation in consequence of osteoblast proliferation or analytes indicating bone resorption as the opposite bone remodeling activity have been recommended as tools in the assessment of bone metastasis in PCa. [2][3][4][5][6][7] The balance between osteoblastic and osteoclastic activity in bone is essentially determined by osteoclastogenesis, which is regulated by 3 proteins: RANK, RANKL and OPG. OPG and RANKL could be, in addition to bone formation and resorption markers, biomarkers to detect bone metastases. 8,9 It was therefore interesting that these 2 proteins were overexpressed in bone metastases of PCa patients. 10,11 Several studies have assessed the diagnostic efficacy of both bone formation and resorption markers for the detection of bone metastases in PCa. 6 However, they often included only a few bone markers or a limited number of patients. 7,12 While little comparative data are available on the diagnostic accuracy of the newly developed assays for the various analytes including OPG and RANKL, the conclusions regarding the diagnostic usefulness need to be reconsidered. 9,13 In addition, the recommendation of diagnostic tests was often substantiated by the univariate evaluation of data without taking into account the usefulness of multivariate analysis. Therefore, our aims were (i) to measure serum markers of bone formation, bone resorption and osteoclastogenesis as noninvasive, easy-to-determine analytes of bone metastases in the same serum samples; (ii) to evaluate and compare the diagnostic validity of all analytes concerning their differential efficiency between patients with and without metastases; (iii) to recom...

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

“…Osteoprotegerin, a pivotal regulator of the osteoclastic activity, (Hofbauer and Schoppet, 2004) has been found to be increased in prostate cancer patients with bone metastases -but not in those with localised diseases (Brown et al, 2001;Jung et al, 2004). In our study, breast cancer patients with or without bone metastases had increased OPG levels compared to healthy controls, contrasting with the absence of elevation found by Lipton et al (2002).…”

“…The pivotal regulator of osteoclastic activity is the system osteoprotegerin (OPG)/receptor activator of NF-kB (RANK)/RANK-ligand (RANKL) , which is involved in physiological as well as pathological conditions, such as metastatic bone disease and multiple myeloma (Chikatsu et al, 2000;Lipton et al, 2002;Park et al, 2003;Vanderkerken et al, 2003). Increase levels of OPG but not RANKL have also been reported in patients with prostate cancer and bone metastases (Jung et al, 2004).…”

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“…Numerous studies analyze the influence of bone metastases of different tumors on bone formation and resorption markers. Jung et al [10] and Kamiya et al [18] find significantly elevated concentrations of different bone formation and resorption markers in case of bone metastases. The results of Halleen et al [11], Lyubimova et al [13], Chao et al [14],and Yao et al [15] show promising findings regarding the bone resorption marker TRACP 5b in the question of bone metastases.…”

“…One approach is the analysis of bone formation and resorption markers, generated in processes of the bone metabolism [10,11,16,18]. Numerous studies analyze the influence of bone metastases of different tumors on bone formation and resorption markers.…”

“…In most cases, merely a venous blood sample is required for laboratory tests. In recent years, numerous bone formation and resorption markers have been analyzed for their diagnostic value in bone metastases of different tumors [10]. One of the most interesting among the bone resorption markers is the tartrate-resistant acid phosphatase 5b (TRACP 5b).…”