This study used a panel of bone markers in order to characterise bone metabolism in children and young adults. New, age-independent parameter namely Formation/Resorption ratio (F/R = Se-BAP + Se-Osteocalcin + Se-Procollagen-C/U-PYD + U-DPD + Se-Crosslaps) is advanced to use in practice.
Abnormal bone metabolism (osteodystrophy, osteopathy, growth retardation, osteoporosis) is the principal complication in some renal disease, bone metabolism has been a focus of interest. Several new biochemical markers to assess bone turnover have been developed over the last decade (1,2). The aim of this study was to investigate the biochemical bone markers in chronic pediatric renal diseases, namely in chronic renal failure (CRF), in kidney transplanted (NTx) children, in idiopathic hypercalciuria (HCaU), in vitamin-D resistant rickets (VDRR) and in idiopathic nephrotic syndrome (INS) patients.
Sixteen children with chronic renal failure (CRF, age 14.5±4.9 years, GFR less than 15 ml/min), 27 kidney transplanted children (NTx, age 17.5±4.8 years, the mean duration of transplantation was 5.0±3.1 years), 7 idiopathic hypercalciuric (HCaU, age 16.4±2.8 years), 7 vitamin-D resistant rickets (VDRR, age 16.1±6.0 years) 5 idiopathic nephrotic (INS, age 13.8±13.8±6.9 years) patients were enrolled into this study and 44 children (age 15.7±6.9 years) without bone and kidney disturbances were used as a control group.
Three type procollagens (PICP Carboxyterminal propeptide of type I. procollagen, ICTP Carboxyterminal cross-linked telopeptide of type I. collagen and PINP Aminoterminal propeptide of type III. procollagen) were investigated by Orion Diagnostica RIA method. ELISA tests were used for serum Bone-specific alkaline phosphatase and Procollagen-C -Collagen type I. C-terminal propeptid (Metra Biosystem), Crosslaps Peptide degradation products of type I. collagen (Osteometer Biotech Corp.) Osteocalcin Bone Gla-protein (Dako) determinations. Urinary pyridinoline (PYD) and Deoxypyridinoline (DPD) excretion were measured by Bio-Rad Crosslink HPLC method. The reference values of children were published in 1999 (3).
The index of bone turnover (Formation/Resorption) was calculated by the following formula:
F/R over {Se-BAP+Se-Osteocalcin+Se-Procollagen-C} over {U-PYD+U-DPD+Se-Crosslaps}
Bone metabolism is characterised by opposite processes of formation and resorption resulting in continuous turnover. The measured biochemical parameters are shown in Table 1. Serum concentrations of all three type procollagens were increased in CRF group and there was no difference in kidney transplanted children. Increased serum concentration of ICTP are seen associated with low GFR, Creatinine - ICTP r=0.780 p<0.001, Creatinine - PICP r=0.059 NS, Creatinine - PINP r=0.168 NS.
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Table 1. The measured biochemical parameters (mean ± SD, * marks significant level vs. control)
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The F/R ratio was higher in NTx patient and lower in HCaU and VDRR children than controls. Figure 1. shows the individual age and F/R ratio in the control group. There is no significant age dependent relationship between them. Figure 2a-f. presents the formation (F) and resorption (R) correlation in the investigated groups. These results suggest that there is an increased osteoblast activity in NTx children (slope 0.58 vs. 1.21 in control) and extended osteoclast activity in HCaU and VDRR groups (intercept + 147 and + 403 vs. -47 in control). Diseases affecting the dynamics of metabolism of the growing skeleton may have long-lasting sequels later in adulthood.
Among our investigated laboratory parameters the PICP (Carboxyterminal propeptide of type I. procollagen) and PIIINP (Aminoterminal propeptide of type III. procollagen) may be a valuable biochemical marker in metabolic bone disease in chronic renal failure patients.
The determination of the F/R ratio in patients with renal disease should prove to be a useful age-independent cumulative indicator of bone metabolism.
1. Blumsohn A., Eastell R.: The performance and utility of biochemical markers of bone turnover: do we know enough to use them in clinical practice? Ann. Clin. Biochem. 1997; 34: 449-459.
2. Griesmacher A.: Biochemical diagnosis in disorders of bone metabolism. Klin Kisérl Lab Med 1999; 26: 47-50.
3. Kenesei É., Reusz Gy., Tóth-Heyn P., Szabó A., Tulassay T.: Pyridinolin és deoxypyridinolin ürítés egészséges és vesebeteg gyermekeknél. Klin Kisérl Lab Med 1999; 26: 16-20.
The study were supported by the OTKA T0311986 and OMFB-TÉT D5/1998 grants.