Parathormone and bone-specific alkaline phosphatase for the follow-up of bone turnover in hemodialysis patients: Is it so simple?

Delanaye, Pierre; Dubois, Bernard; Jouret, François; Krzesinski, Jean-Marie; Moranne, Olivier; Cavalier, Étienne

doi:10.1016/j.cca.2012.12.009

Cited by 7 publications

(8 citation statements)

References 20 publications

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“…Due to these different backgrounds, it can be expected that there is no clear correlation between biomarkers even if they reflect the same biological process in bone. Indeed, while PTH can be considered a driver of bone turnover, its association with BSAP, an indicator of osteoblastic activity, is generally vague in patients on dialysis when longitudinally assessed [ 9 ]. This may in part be explained by CKD-associated PTH-resistance, which can consist of either posttranslational modification of PTH rendering it biologically inactive, or end-organ resistance to its actions [ 10 ].…”

Section: The Interplay Between Bone Markersmentioning

confidence: 99%

Circulating markers of bone turnover

Vervloet

Brandenburg

2017

J Nephrol

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Renal osteodystrophy is a feature of chronic kidney disease (CKD), with increasing prevalence as CKD progresses. This bone disease is responsible for major morbidity, including fractures, and a deterioration in the quality of life and its sequelae. Circulating biomarkers of renal osteodystrophy typically indicate bone turnover, but not other features of bone, like bone volume, mineralization, quality or strength. Bone turnover can be considered to be primarily a reflection of bone cell activity, in particular that of osteoblasts and osteoclasts. Since current treatments for bone disease usually target cellular activity, biomarkers are considered to be able to contribute to the decision-making for treatment and its follow-up. In CKD, one has to consider the impact of a diminished clearance of biomarkers or their altered metabolism, both potentially limiting its clinical use. Here, several aspects of the most frequently used biomarkers of bone turnover are reviewed, with an emphasis on the specific situation represented by CKD. This review is based on the overview lecture at the symposium held in Amsterdam, September 23, 2016: “The Bone In CKD”, organized by the CKD-MBD working group of ERA-EDTA.

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Section: The Interplay Between Bone Markersmentioning

confidence: 99%

Circulating markers of bone turnover

Vervloet

Brandenburg

2017

J Nephrol

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“…In the current analysis, we studied the evolution and, more specifically, the concordance between variations of biomarkers over time. If we confirmed that baseline or one-year results of PTH and bone biomarkers are highly correlated in cross-sectional analyses 3 , 9 – 11 , the correlations are much less relevant if the variations or changes of biomarkers are considered, suggesting that PTH and bone biomarkers give different information 8 . In this analysis, the variable “time” seems particularly important.…”

Section: Discussionmentioning

confidence: 82%

“…However, the interpretation of these two parameters is not easy, notably because of lack of standardization in the dosages 6 – 8 . In cross-sectional studies, a good correlation is found between the two biomarkers 3 , 9 – 11 . However, their performance to predict bone turnover assessed by bone biopsies in transversal studies remains actually disappointing 3 , 12 – 14 .…”

Section: Introductionmentioning

confidence: 91%

“…For this reason, the revised 2017 KDIGO guidelines suggest that potential CKD-MBD therapies should be based on serial assessments of biomarkers, and thus on trends or variations (Δ), more than on one-single transversal result. In a previous work, we suggested that the correlations between variations of PTH (ΔPTH) and b-ALP (Δb-ALP) were poor 11 . This study was however retrospective and sample size was limited.…”

Section: Introductionmentioning

confidence: 99%

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Variations of parathyroid hormone and bone biomarkers are concordant only after a long term follow-up in hemodialyzed patients

Delanaye

Warling

Moonen

et al. 2017

Sci Rep

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End-stage renal disease is associated with mineral and bone disorders. Guidelines recommending therapies should be based on serial assessments of biomarkers, and thus on variations (Δ), rather than scattered values. We analyzed the correlations between ΔPTH and Δbone biomarkers such as bone-specific alkaline phosphatase (b-ALP), Beta-CrossLaps (CTX), osteocalcin, intact serum procollagen type-1 N-propeptide (P1NP), and tartrate-resistant acid phosphatase 5B (TRAP-5B) at different time-points. In this prospective observational analysis, variations of biomarkers were followed after 6-week (n = 129), 6-month (n = 108) and one-year (n = 93) period. Associations between variations were studied by univariate linear regression. Patients followed for one-year period were classified (increaser or decliner) according to variations reaching the critical difference. Over the 6-week period, only ΔCTX was correlated with ΔPTH (r = 0.38, p < 0.0001). Over the one-year period, correlations between ΔPTH and Δbone biomarkers became significant (r from 0.23 to 0.47, p < 0.01), except with ΔTRAP-5b. Correlations between Δbone biomarkers were all significant after one-year period (r from 0.31 to 0.68, p < 0.01), except between Δb-ALP and ΔTRAP-5b. In the head-to-head classifications (decliners/increasers), the percentage of concordant patients was significantly higher over the one-year than the 6-week period. A concordance between ΔPTH and Δbone biomarkers is observed in dialysis patients, but only after a long follow-up.

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“…Bone-specific alkaline phosphatase (ALP) is a glycoprotein. It is found on the surface of osteoblasts and is a more specific measure of bone formation as well as bone turnover (Delanaye et al 2013). Li et al showed that ALP activity was almost completely inhibited when connexin Cx43 antisense cDNA was stably transfected into the immortalized human fetal osteoblastic cell line hFOB1.19, despite only a 50% decrease in cell-to-cell communication (Li et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Gap junction mediated regulation of osteocytes to osteoblastic alkaline phosphatase activity is independent of microgravity

Meng

Xie

2014

Animal Cells and Systems

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Decreased bone formation is one of the main causes of bone loss under microgravity. As a mechanical perceiver, osteocyte regulates bone formation by sending mechanical signals to osteoblast. However, the regulation of osteoblastic bone formation by osteocytes is less known so far under the microgravity conditions. The aim of this study was to investigate the regulation of bone formation/loss by detection of the osteocytic regulatory effects on the bone-specific alkaline phosphatase (ALP) activity of osteoblasts under altered gravitational environment. The altered gravitational environment was provided by a large gradient high magnetic field that could produce high magneto-gravitational environment (HMGE) and provided three apparent gravity levels (µg, 1g, and 2g). After the MLO-Y4 and 2T3 cells were cocultured in direct physical contact for 24 h and established gap junction intercellular communication under HMGE, a highly significant rapid increase in ALP activity was observed in µg, 1g, 2g, and control group (p < 0.001). Conversely, application of 50-µM beta-glycyrrhetinic acid gap junction inhibitor or remote coculture significantly decreased the ALP activity. There were no obvious differences of osteoblastic 2T3 ALP activity among µg, 1g, 2g, and control groups. Based on these findings, we interpreted that gap junction was probably the main route of osteoblastic ALP activity regulation by osteocyte. Gravity had no significant impact on the osteoblastic ALP activity regulated by osteocyte in a short period of time.

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Parathormone and bone-specific alkaline phosphatase for the follow-up of bone turnover in hemodialysis patients: Is it so simple?

Abstract: This study shows the lack of correlation between ΔPTH and Δb-ALP over time in patients under chronic hemodialysis.

Cited by 7 publications

References 20 publications

Circulating markers of bone turnover

Circulating markers of bone turnover

Variations of parathyroid hormone and bone biomarkers are concordant only after a long term follow-up in hemodialyzed patients

Gap junction mediated regulation of osteocytes to osteoblastic alkaline phosphatase activity is independent of microgravity

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