LAUSR

Parathyroid hormone (PTH) is a key regulator of bone turnover. PTH can be oxidized in vivo, which impacts biological activity. Variable PTH oxidation may be hypothesized to contribute to the rather poor correlation of PTH with indices of bone turnover. Non-oxidized PTH may better reflect the hormonal function than currently measured intact PTH (iPTH). Therefore, we investigated whether n-oxPTH would be superior compared to iPTH as indicator of bone turnover in ESRD. Thirty patients with a wide range of bone turnover, as assessed by bone histomorphometry (BHM), were selected from an ongoing, prospective observational study in patients with ESRD (NCT01886950), that underwent bone biopsy. Both iPTH (Cobas, Roche Diagnostics, Rotkreuz, Switzerland) and n-oxPTH (A1112; Immundiagnostik AG, Bensheim, Germany) and in addition bone turnover markers (bone-specific alkaline phosphatase (BSAP), P1NP and tartrate-resistant acid phosphatase 5b (TRAP5b)) were assessed in blood samples taken at the time of the bone biopsy. Descriptive statistics, Pearson correlation, regression analysis and ROC curves were used to assess the discriminative ability of n-oxPTH vs iPTH to detect bone turnover. n-oxPTH and iPTH were strongly correlated (r=0.96; p<0.001) and n-oxPTH values were on average 87% lower than iPTH values. Bone turnover, assessed by BHM (both static and dynamic measures) were strongly correlated with n-oxPTH and iPTH, e.g. bone formation rate r=0.65; p<0.001 and r=0.69; p<0.001, respectively. Bone turnover markers (BSAP, P1NP and TRAP5b) were also strongly and similarly associated with n-oxPTH and iPTH. The AUROC values for discriminating between low/non-low turnover for n-oxPTH and iPTH were 0.81; p<0.01 and 0.86; p<0.01, respectively (Figure 1A). For high/non-high turnover the AUROC was 0.88; p<0.01 and 0.90; p<0.01, respectively (Figure 1B). n-oxPTH was not superior compared to iPTH in discriminating between high/non-high and low/non-low turnover and also showed no stronger correlation to biomarkers of bone turnover. Therefore, we conclude that there is no added value of n-oxPTH for evaluating bone disease in ESRD patients receiving dialysis, using the currently available method. Since this method cannot distinguish partially form completely oxidized PTH, we cannot definitely rule out the possibility that oxidation of PTH has impact on bone turnover .