Circulating markers of bone turnover

Vervloet, Marc G.; Brandenburg, Vincent

doi:10.1007/s40620-017-0408-8

Cited by 54 publications

(39 citation statements)

References 55 publications

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“…Patients with CKD have even greater rates of vitamin K deficiency as compared to the general population. The number of CKD patients who have vitamin K deficiency reaches 70-90% of that population [50,51,52] (Table 1). Poor oral intake of vitamin K is the main cause of deficiency [50,53].…”

Section: Vitamin K In Chronic Kidney Disease (Ckd)mentioning

confidence: 99%

Vitamin K effects in human health: new insights beyond bone and cardiovascular health

et al. 2019

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Vitamin K is a cofactor for the function of the enzyme γ-glutamyl carboxylase, necessary for the activation of multiple vitamin K dependent-proteins. Vitamin K dependent-proteins (VKDPs) have important roles in bone health, vascular health, metabolism, reproduction as well as in cancer progression. Vitamin K deficiency is common in different conditions, including kidney disease, and it may influence the activity of VKDPs. This review discusses vitamin K status in human health and the physiologic and pathologic roles of VKDPs, beyond the established effects in skeletal and cardiovascular health.

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Section: Vitamin K In Chronic Kidney Disease (Ckd)mentioning

confidence: 99%

Vitamin K effects in human health: new insights beyond bone and cardiovascular health

et al. 2019

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“…Although these two methods have different measuring principles, the obtained comparison parameters in this study present good agreement between two independent methods for bALP determination, after we have conversed measured concentrations to the same units. Although, so far, there are not many published studies analyzing the comparison of the electrophoretic and immunochemical method of bALP determination, the literature data generally indicate an inappropriate agreement between the methods (2,4,6). In addition, data analyses and interpretation is complicated issue that has been discussed for decades and still there is no gold standard for statistical procedure that should be used for method comparison data analyses (13).…”

Section: Discussionmentioning

confidence: 99%

Comparison between bone alkaline phosphatase immunoassay and electrophoresis technique in hemodialysis patients

Milinković

Sarić-Matutinović

Pejanović³

et al. 2019

Journal of Medical Biochemistry

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Summary Background Problem of the variability between the different methods using for bone alkaline phosphatase (bALP) determination greately influences the clinical significance of bALP as direct marker of bone metabolism. The aim of this study was to compare immunoassay with electrophoresis technique for bALP determination. Methods We measured bALP in 71 patients on hemodialysis with agar gel electrophoresis (ISO-PAL, SEBIA) and immunoassay (OSTASE, Beckman Coulter). Results The analyzed methods showed significant correlation (Spearman’s rho: 0.776, P < 0.01), but we found statistically significant (P < 0.01) positive bias (27%) for the results measured by immunoassay. In support of this, using electrophoresis technique we have detected presence of the intestinal isoenzymes of alkaline phosphatase in 55% of patients with median value of 30% of the total alkaline phoshatase and presence of liver-2 alkaline phosphatase isoform in 42% of patients with median value of 16.6%. The Kendall’s W of 0.787 (P<0.0001) revealed significant concordance between two analysed methods. Cusum test showed no significant deviation from linearity (P=0.850). Conclusions Despite good agreement between immunoassay methods and electrophoresis technique for bALP determination, interchangeability between these two methods is questionable. Although immunoassays are increasingly used, as fully automated methods, in a large number of laboratories and become routine methods for bALP determination, it should be beared in mind, besides various interferences, also the heterogeneity of the bALP itself, especially in patients on hemodialysis.

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“…Total serum ALP activity was increased in CKD mice in our study. Similarly, bone-specific ALP is typically increased in patients with high turnover CKD-MBD ( 40 ). ALP activity in serum originates in about equal parts from bone and liver, with TNAP being the major isoenzyme found in blood ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…The plasma clearance of collagen crosslinks depends on kidney function ( 42 ). Therefore, serum collagen crosslink concentrations are not considered suitable markers of bone resorption in CKD patients ( 40 ). Under normal circumstances, urinary collagen crosslink excretion is the best estimate of whole body bone resorption activity in mice, because osteoclast numbers are often not indicative of osteoclast resorptive activity ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that circulating intact PTH is one of the main drivers of bone turnover in CKD patients. Hence, serum intact PTH is a useful biomarker to discriminate between low and high bone turnover in CKD patients ( 17 ), albeit its sensitivity to dissect high and low bone turnover disease is only about 65% ( 17 , 40 ). What is actually causing the often observed impairment in bone mineralization in bone biopsies of CKD patients is not well known ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

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Augmented Fibroblast Growth Factor-23 Secretion in Bone Locally Contributes to Impaired Bone Mineralization in Chronic Kidney Disease in Mice

et al. 2018

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism caused by CKD. Impaired bone mineralization together with increased bony secretion of fibroblast growth factor-23 (FGF23) are hallmarks of CKD-MBD. We recently showed that FGF23 suppresses the expression of tissue nonspecific alkaline phosphatase (TNAP) in bone cells by a Klotho-independent, FGF receptor-3-mediated signaling axis, leading to the accumulation of the mineralization inhibitor pyrophosphate. Therefore, we hypothesized that excessive FGF23 secretion may locally impair bone mineralization in CKD-MBD. To test this hypothesis, we induced CKD by 5/6 nephrectomy in 3-month-old wild-type (WT) mice and Fgf23−/−/VDRΔ/Δ (Fgf23/VDR) compound mutant mice maintained on a diet enriched with calcium, phosphate, and lactose. Eight weeks postsurgery, WT CKD mice were characterized by reduced bone mineral density at the axial and appendicular skeleton, hyperphosphatemia, secondary hyperparathyroidism, increased serum intact Fgf23, and impaired bone mineralization as evidenced by bone histomorphometry. Laser capture microdissection in bone cryosections showed that both osteoblasts and osteocytes contributed to the CKD-induced increase in Fgf23 mRNA abundance. In line with our hypothesis, osteoblastic and osteocytic activity of alkaline phosphatase was reduced, and bone pyrophosphate concentration was ~2.5-fold higher in CKD mice, relative to Sham controls. In Fgf23/VDR compound mice lacking Fgf23, 5/6-Nx induced secondary hyperparathyroidism and bone loss. However, 5/6-Nx failed to suppress TNAP activity, and bone pyrophosphate concentrations remained unchanged in Fgf23/VDR CKD mice. Collectively, our data suggest that elevated Fgf23 production in bone contributes to the mineralization defect in CKD-MBD by auto-/paracrine suppression of TNAP and subsequent accumulation of pyrophosphate in bone. Hence, our study has identified a novel mechanism involved in the pathogenesis of CKD-MBD.

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Circulating markers of bone turnover

Cited by 54 publications

References 55 publications

Vitamin K effects in human health: new insights beyond bone and cardiovascular health

Vitamin K effects in human health: new insights beyond bone and cardiovascular health

Comparison between bone alkaline phosphatase immunoassay and electrophoresis technique in hemodialysis patients

Augmented Fibroblast Growth Factor-23 Secretion in Bone Locally Contributes to Impaired Bone Mineralization in Chronic Kidney Disease in Mice

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