Biological variability in assessing the clinical value of biochemical markers of bone turnover

Plebani, Mario; Bernardi, Daniela Miotto; Meneghetti, Maria Francesca; Ujka, Francesca; Zaninotto, Martina

doi:10.1016/s0009-8981(00)00285-0

Cited by 22 publications

(7 citation statements)

References 20 publications

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“…Analyses were performed in both serum and urine, but consistent results were not always described. The preanalytic variability of bone markers, their different stability in vitro especially in urine and use of assays with different antibodies recognizing different epitopes may explain many of the discrepant results 23, 24, 25, 26, 27. To avoid these discrepancies as far as possible, we measured bone markers exclusively in serum collected during a defined time period, between 7:00 and 9:00 A.M.…”

Section: Discussionmentioning

confidence: 99%

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

Jung

Lein

Stephan

et al. 2004

Intl Journal of Cancer

195

141

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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...

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Section: Discussionmentioning

confidence: 99%

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

Jung

Lein

Stephan

et al. 2004

Intl Journal of Cancer

195

141

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“…BTMs show wide biological variability both in healthy subjects and in patients with metabolic bone disease ( 38–41 ). All sources of variability‐biological and analytical, intra‐ and interassay, intra‐ and interindividual‐must be accounted for to interpret clinical BTM measurements accurately ( 42 ).…”

Section: Clinical Utility Of Bone Turnover Markersmentioning

confidence: 99%

“…The biological (preanalytical) variability of BTM measurements normally exceeds the analytical variability( 39 ) and derives from both controllable and uncontrollable sources ( 50 ). Controllable sources include fasting versus nonfasting state,( 51,52 ) calcium intake, physical exercise, smoking and alcohol use,( 53 ) diurnal and seasonal variations, and phase of the menstrual cycle ( 50,54 ).…”

Section: Clinical Utility Of Bone Turnover Markersmentioning

confidence: 99%

Perspective: Assessing the Clinical Utility of Serum CTX in Postmenopausal Osteoporosis and Its Use in Predicting Risk of Osteonecrosis of the Jaw

Baim

Miller

2009

Journal of Bone and Mineral Research

126

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Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate-treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C-telopeptide crosslink of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Recently, sCTX has been singled out as a potential indicator of risk of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates who require oral surgery. However, whether BTMs are capable of predicting ONJ risk and whether sCTX is usable for this purpose are controversial questions. This article presents an overview of the current literature regarding critical issues affecting the clinical utility of BTMs (including variability and reference ranges) and the current applications of BTMs in PMO management, with a focus on sCTX. Last, the appropriateness of using sCTX to predict ONJ risk in women receiving oral bisphosphonates for PMO is evaluated.

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“…Analyses were performed in both serum and urine, but consistent results were not always described. The pre-analytic variability of BTMs, their different stability in vitro especially in urine and use of assays with different antibodies recognizing different epitopes may explain many of the discrepant results [28] , [29] , [30] , [31] . Seibel [32] indicated serum as the preferred matrix for measurement.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic validity of serum bone turnover markers in bone metastatic non-small cell lung cancer patients

Wang

Qiao

et al. 2015

Journal of Bone Oncology

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Biological variability in assessing the clinical value of biochemical markers of bone turnover

Cited by 22 publications

References 20 publications

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

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

Perspective: Assessing the Clinical Utility of Serum CTX in Postmenopausal Osteoporosis and Its Use in Predicting Risk of Osteonecrosis of the Jaw

Diagnostic and prognostic validity of serum bone turnover markers in bone metastatic non-small cell lung cancer patients

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