Background
PTH can be oxidized in vivo, which reduces its biological activity. A new method enables selective quantification of non-oxidized PTH (n-oxPTH). PTH is frequently measured in patients with chronic kidney disease (CKD) and considered to reflect bone turnover. n-oxPTH may better reflect the hormonal function than currently measured total PTH (tPTH). Therefore, we investigated whether n-oxPTH would be superior compared to tPTH as indicator of bone turnover in CKD.

Methods
Thirty patients with a wide range of bone turnover were included from an ongoing, prospective observational study in patients with CKD referred for renal transplantation (NCT01886950). Bone biopsies were taken and serum bone turnover markers, n-oxPTH and tPTH were determined. Pearson correlation, regression analysis and ROC curves were used to assess the association of n-oxPTH vs tPTH with bone turnover.

Results
n-oxPTH and tPTH had a strong correlation (r=0.96; p<0.001) and n-oxPTH values were on average 87% lower than tPTH values. Also, n-oxPTH and tPTH showed highly similar correlation coefficients with bone turnover markers (BSAP, P1NP, TRAP5b), and both static and dynamic measures of bone turnover based on bone biopsies (e.g. bone formation rate r=0.65; p<0.001 and r=0.69; p<0.001, respectively). The AUROC values for discriminating between low/non-low turnover for n-oxPTH and tPTH were 0.81; p<0.01 and 0.86; p<0.01, respectively. For high/non-high turnover the AUROC was 0.88; p<0.01 and 0.90; p<0.01, respectively.

Conclusions
n-oxPTH was not superior compared to tPTH in discriminating between high/non-high and low/non-low turnover and also showed no stronger correlation to markers of bone turnover. This suggests that there is no added value of n-oxPTH for evaluating bone disease in CKD. A possible explanation for this unexpected result might lie in the specificity of the n-oxPTH assay, which fails to measure a partially oxidized and active form of PTH. Further studies with focus on quantification of the separate oxidized forms of PTH is therefore recommended.