Impact of upacicalcet on bone metabolism in hemodialysis patients with secondary hyperparathyroidism: a post-hoc analysis

Secondary hyperparathyroidism (SHPT) is a complication prevalent among patients undergoing hemodialysis (HD). Upacicalcet, a novel intravenous calcimimetic agent, has demonstrated efficacy in improving bone turnover by suppressing PTH production. However, the influence of baseline bone metabolism on the efficacy of calcimimetics remains unclear. Therefore, we aimed to evaluate the efficacy of upacicalcet on PTH suppression and changes in bone turnover based on bone-specific alkaline phosphatase (BAP) levels. This study involved a post-hoc analysis of data from a phase 3, placebo-controlled, double-blind trial evaluating the effect of upacicalcet in HD patients with SHPT. Patients were categorized into 3 groups based on tertiles of baseline serum BAP levels. Key biomarkers, including serum levels of intact PTH (iPTH), BAP, tartrate-resistant acid phosphatase-5b (TRACP-5b), and BAP/TRACP-5b ratio, were measured. Percentage changes from baseline in these parameters were assessed using a mixed-effects model for repeated measures. Additionally, cases of increased serum BAP levels following upacicalcet administration were investigated. A total of 103 HD patients with SHPT treated with upacicalcet were included in the analysis. Patients were categorized into low BAP (<12.8 μg/L), medium BAP (12.8-18.8 μg/L), and high BAP (>18.8 μg/L) groups. After 24 wk of upacicalcet intervention, iPTH levels decreased across all baseline BAP groups. Serum BAP and TRACP-5b levels decreased, whereas the BAP/TRACP-5b ratio increased across all groups. However, 26 (27.4%) patients exhibited increased BAP levels at week 24 relative to the levels at baseline despite the significant reduction in PTH levels. Upacicalcet treatment reduced PTH levels in HD patients with SHPT, regardless of baseline BAP levels. The concurrent increase in the BAP/TRACP-5b ratio with upacicalcet suggests that this agent may exert direct effects on bone metabolism, in addition to its role in suppressing parathyroid activity.