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      Bone Alkaline Phosphatase besides Intact Parathyroid Hormone in Hemodialysis Patients – Any Advantage?

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          Background/Aim: Bone alkaline phosphatase (bAP) is known to be an important biochemical marker of bone formation. Through the present study, we intended to find out whether there is any advantage in bAP determination, as a routine biochemical marker, besides intact parathyroid hormone (iPTH) in hemodialysis patients. Methods: In a population of 140 hemodialysis patients, bAP and iPTH were determined on four quarterly consecutive occasions. According to the values of iPTH (pg/ml) and bAP (ng/ml), patients were divided into four groups: group I: iPTH >200 and bAP >20, group II: iPTH >200 and bAP <20, group III: iPTH <200 and bAP <20 and group IV: iPTH <200 and bAP >20. Patients with higher serum phosphorus (P) (group A: p ≧7 mg/dl) were compared with those with lower serum P levels (group B: p <7 mg/dl). Results: The global correlation between iPTH and bAP (total evaluations, n = 503) was 0.32 (p < 0.001). Group IV patients tended to show a slight increase of serum aluminum (sAl) levels, which were 12.48 ± 5.35 µg/l higher than in the patients from group I (sAl = 9.97 ± 4.39 µg/l), group II (sAl = 10.86 ± 4.45 µg/l) or group III (sAl = 10.92 ± 3.92 µg/l). Significance values (Mann-Whitney) in each group, in comparison with group IV, were the following: group I: 0.004; group II: 0.062; group III: <0.001. Group A (n = 66) showed higher iPTH levels than group B (n = 430), although bAP and sAl were both similar in these two groups of patients (Mann-Whitney): iPTH (A) = 631.0 ± 487.7 vs. iPTH (B) = 253.3 ± 191.6, p < 0.001; bAP (A) = 22.9 ± 17.4 vs. bAP (B) = 20.4 ± 13.1, p = n.s.; sAl (A) = 10.2 ± 3.5 vs. sAl (B) = 10.8 ± 4.4, p = n.s. For similar Al and bAP values, group A showed a much stronger iPTH/bAP correlation than group B: r = 0.67 (p < 0.001) vs. r = 0.30 (p < 0.001), respectively. Conclusion: Although iPTH and bAP are frequently in agreement, it seems important to separate parathyroid activity given by iPTH, from bone remodelling reflected by bAP, in the presence of either a higher aluminum exposition or a well-controlled phosphatemia.

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          Most cited references 10

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          Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy.

          Intermittent calcitriol therapy is commonly used to treat secondary hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of secondary hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 +/- 380 to 150 +/- 170 microns2/mm2/day, P < 0.001. Bone formation decreased to normal in six patients, but six patients developed adynamic lesions of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone formation at follow-up evaluation. Neither the mean dose of calcitriol nor the average dose per kilogram body weight differed in patients with adynamic lesions. Thus, adynamic renal osteodystrophy develops in a substantial number of patients during intermittent calcitriol therapy. Although declining serum PTH and alkaline phosphatase levels suggest the development of the adynamic lesion, bone formation decreases in some patients despite persistently high serum PTH levels. Calcitriol may directly suppress osteoblastic activity in patients with secondary hyperparathyroidism when given in large doses to patients undergoing peritoneal dialysis.
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            Circulating biochemical markers of bone remodeling in uremic patients.

             R Melero,  P Ureña (1999)
            Chronic renal failure is often associated with bone disorders, including secondary hyperparathyroidism, aluminum-related low-turnover bone disease, osteomalacia, adynamic osteopathy, osteoporosis, and skeletal beta2-microglobulin amyloid deposits. In spite of the enormous progress made during the last few years in the search of noninvasive methods to assess bone metabolism, the distinction between high- and low-turnover bone diseases in these patients still frequently requires invasive and/or costly procedures such as bone biopsy after double tetracycline labeling, scintigraphic-scan studies, computed tomography, and densitometry. This review is focused on the diagnostic value of several new serum markers of bone metabolism, including bone-specific alkaline phosphatase (bAP), procollagen type I carboxy-terminal extension peptide (PICP), procollagen type I cross-linked carboxy-terminal telopeptide (ICTP), pyridinoline (PYD), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) in patients with chronic renal failure. Most of the observations made by several groups converge to the conclusion that serum bAP is the most sensitive and specific marker to evaluate the degree of bone remodeling in uremic patients. Nonetheless, PYD and osteocalcin, in spite of their retention and accumulation in the serum of renal insufficient patients, are also excellent markers of bone turnover. The future generalized use of these markers, individually or in combination with other methods, will undoubtedly improve the diagnosis and the treatment of the complex renal osteodystrophy.
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              Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis patients.

              Renal osteodystrophy includes a number of low and high turnover bone histologic patterns which require a bone biopsy for their full identification. The role of intact PTH and several classical and more recent bone markers in the non-invasive diagnosis of renal bone disease in patients with CRF in HD requires further definition since available published data are limited. In addition to intact PTH, alkaline phosphatase (AP) and osteocalcin (BGP), bone alkaline phosphatase isoenzyme (BALP), tartrate resistant acid phosphatase (TRAP), C-terminal cross-linked peptide of collagen type 1 (ICTP) and deoxypyridinoline (DPD) were measured in the serum of 41 patients on haemodialysis, subjected at the same time to transiliac bone biopsy for histomorphometric, histodynamic and aluminium histochemical examination. Histodynamic evaluation following double tetracycline label, was carried out in 37 patients. The patients had no evidence of active cytolytic and cholestatic liver disease and a history of very limited aluminium exposure. The patients had differing degrees of hyper-parathyroidism, with intact PTH ranging from normal to very elevated levels. Serum values of the markers BGP, ICTP and DPD, normally excreted through the kidneys, were on average very high. The correlation coefficients of the humoral parameters vs dynamic variables, such as BFR/BS, were high. The highest values were: intact PTH 0.798, AP 0.900, BALP 0.891, ICTP 0.807. The patients, grouped in low turnover osteodystrophy (LTO; 9), mixed osteodystrophy (MO; 9) and prevalent hyperparathyroidism (HP; 23), showed significant difference in the levels of most humoral and static and dynamic parameters (ANOVA). Bone aluminium histochemistry was negative in all cases. Discrimination of LTO patients from the other groups by humoral parameters, at the highest value of accuracy, showed 100% sensitivity and 93.7% specificity with a cut-off of 12.9 ng/ml for BALP; 88.9% sensitivity and 93.7% specificity with a cut-off of 21.5 ng/ml for DPD, and 88.9% sensitivity and 90.6% specificity with a cut-off of 79.7 pg/ml for intact PTH. The other markers had lower values. A standardized z-score approach for evaluation of all humoral parameters was also carried out. Using all variables, a correct classification of MO/HP and of LTO was possible in 93.8 and 88.9% of the cases, respectively. Predictive power was 96.8 and 80%, respectively for MO/HP and LTO. When the only variables used were intact PTH and BALP, a correct classification of MO/HP and LTO was possible in 90.6% and 88.9%, respectively. Predictive value of MO/HP was 96.7% and for LTO 72.7%. Predictive values using PTH and AP were 96.3% and 57.2%, respectively. Intact PTH and several relatively new bone markers are of certain value in the non-invasive diagnosis of renal osteodystrophy. However some of the humoral markers carry the same quality of information and the use of intact PTH and BALP may be adequate in the discrimination of bone histologic patterns. In cases exempt from liver disease, PTH and AP may be used as a less costly alternative. Bone biopsy could be chiefly limited to cases with borderline humoral values and to all those with a suspected aluminium overload.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                November 2005
                06 July 2005
                : 101
                : 3
                : c122-c127
                Hemodial – Centro de Hemodiálise de Vila Franca de Xira, Vila Franca de Xira, Portugal
                86682 Nephron Clin Pract 2005;101:c122–c127
                © 2005 S. Karger AG, Basel

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                Figures: 2, Tables: 2, References: 15, Pages: 1
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