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      Measurement of PTH Fragments for Assessment of Renal Bone Disease in Hemodialysis Patients

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          Background: Renal bone pathology involves a spectrum from ‘high-turnover’ to ‘low-turnover bone disease’ (adynamic bone disease, classical osteomalacia). The diagnosis of the latter usually requires bone biopsy. Inhibitory parathyroid hormone (PTH) fragments may be useful for its noninvasive diagnosis. Methods: A cross-sectional study was performed in 54 patients on chronic hemodialysis which involved measurements of intact PTH (iPTH; Nichols assay), total PTH (tPTH; Scantibodies assay), and the cyclase-activating PTH fragment (CAP). The level of cyclase-inactive PTH fragment (CIP) was calculated. At the same time, serum calcium, phosphorus, and alkaline phosphatase levels as well as the current therapy for secondary hyperparathyroidism were recorded. In selected patients, bone radiographs were evaluated for osteitis fibrosa. Results: A high correlation (r = 0.94) was found between iPTH and tPTH, with the tPTH levels being lower by 30–40%. A similar association was also found for CAP (r = 0.988) and for CIP (r = 0.93). 3 out of the 54 patients had a CAP/CIP ratio of ≤1 which has been associated with adynamic bone disease. A higher CIP ratio was significantly associated with the use of aluminum-hydroxide- and calcium-containing phosphate binders. Conclusions: iPTH and tPTH assays are highly correlated. In a general hemodialysis patient population, low-turnover bone disease appears to be rare, when the CAP/CIP ratio is used as a marker. A high CIP value was associated with therapy using aluminum hydroxide, a drug known to carry a risk of adynamic bone disease.

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          Most cited references 12

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          Improved assessment of bone turnover by the PTH-(1-84)/large C-PTH fragments ratio in ESRD patients.

           H Mawad,  M Faugere,  Z. Geng (2001)
          The "intact" parathyroid hormone (PTH) assay recognizes PTH-(1-84) as well as amino terminally truncated PTH fragments, that is, large carboxyterminal PTH fragments (C-PTH fragments). The present study investigated whether the use of the plasma PTH-(1-84)/C-PTH fragment ratio enhances the noninvasive assessment of bone turnover in patients on dialysis. Bone biopsies and blood samples for determinations of routine indices of bone turnover and PTH peptides were obtained in 51 adult patients on dialysis not treated with drugs affecting bone such as vitamin D or corticosteroids. Blood levels of large C-PTH fragments were calculated by subtracting PTH-(1-84) from "intact" PTH. Patients were classified according to their levels of bone turnover based on histomorphometrically obtained results of activation frequency. Prediction of bone turnover by the various blood indices was done by using proper statistical methods. In addition, hypercalcemia was induced by calcium gluconate infusion in a subset of patients, and levels of PTH-(1-84), "intact" PTH, and PTH-(1-84)/C-PTH fragment ratio were determined. The PTH-(1-84)/C-PTH fragment ratio was the best predictor of bone turnover. A ratio> 1 predicted high or normal bone turnover (sensitivity 100%), whereas a ratio <1 indicated a high probability (sensitivity 87.5%) of low bone turnover. Calcium infusion resulted in decrease in PTH-(1-84)/C-PTH fragment ratio. The PTH-(1-84)/C-PTH fragment ratio predicts bone turnover with acceptable precision for biological measurements. Moreover, a change in serum calcium levels is one of the regulators of the relative amount of circulating PTH-(1-84) and its large C-PTH fragments.
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            Useful biochemical markers for diagnosing renal osteodystrophy in predialysis end-stage renal failure patients.

            Various biochemical markers have been evaluated in dialysis patients for the diagnosis of renal osteodystrophy (ROD). However, their value in predialysis patients with end-stage renal failure (ESRF) is not yet clear. Bone histomorphometric evaluation was performed and biochemical markers of bone turnover were determined in serum of an unselected predialysis ESRF population (N = 84). Significant (P < 0.005) differences between the five groups with ROD (ie, normal bone [N = 32], adynamic bone [ABD; N = 19], hyperparathyroidism [N = 8], osteomalacia [OM; N = 10], and mixed lesion [N = 15]) were noted for intact parathyroid hormone, total (TAP) and bone alkaline phosphatase (BAP), osteocalcin (OC), and serum calcium levels. Serum creatinine and (deoxy)pyridinoline levels did not differ between groups. For the diagnosis of ABD, an OC level of 41 microg/L or less (< or =7.0 nmol/L) had a sensitivity of 83% and specificity of 67%. The positive predictive value (PPV) for the population under study was 47%. The combination of an OC level of 41 ng/L or less (< or =7.0 nmol/L) with a BAP level of 23 U/L or less increased the sensitivity, specificity, and PPV to 72%, 89%, and 77%, respectively. ABD and normal bone taken as one group could be detected best by a BAP level of 25 U/L or less and TAP level of 84 U/L or less, showing sensitivities of 72% and 88% and specificities of 76% and 60%, corresponding with PPVs of 89% and 85%, respectively. In the absence of aluminum or strontium exposure, serum calcium level was found to be a useful index for the diagnosis of OM. OC, TAP, BAP, and serum calcium levels are useful in the diagnosis of ABD, normal bone, and OM in predialysis patients with ESRF.
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              Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy.


                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                October 2006
                06 October 2006
                : 29
                : 3
                : 175-181
                Division of Nephrology, Kantonsspital St. Gallen, St. Gallen, Switzerland
                95351 Kidney Blood Press Res 2006;29:175–181
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 1, References: 14, Pages: 7
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/95351
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