Lower Bone Turnover and Skeletal PTH Responsiveness in Japanese Compared to European Patients on Hemodialysis

Abstract

Abstract Context Parathyroid hormone (PTH) treatment targets for patients receiving hemodialysis (HD) are lower in Japan than in Europe. Whether this translates to lower bone turnover is unknown and could depend on skeletal PTH responsiveness. Objective This study investigates whether skeletal PTH responsiveness is better preserved in Japanese vs European patients receiving HD. Methods This is a post hoc analysis of data from 2 prospective cohort studies, using a case-control design. Patients receiving chronic intermittent HD therapy were eligible for inclusion. Participating Belgian and Japanese patients (n = 374) were matched 1:1 by age (59 ± 12 years), sex (66% male), diabetes (34%), and dialysis duration (39 months [22-63 months]). PTH, bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured centrally in Liège, Belgium. Results Japanese patients had lower levels of iPTH (207 vs 268 pg/mL; P < .001), BALP (15.3 vs 24.5 μg/L; P < .001), and TRAP5b (3.35 vs 5.79 U/L; P < .001). Linear regression analyses revealed lower levels of bone turnover markers for any given level of PTH in Japanese vs Belgian patients, indicating lower skeletal PTH responsiveness. Consistently, bone turnover markers were significantly lower in Japanese vs Belgian patients when stratifying or matching according to PTH levels. Male sex, obesity, and hyperphosphatemia were the main determinants of the bone turnover marker/PTH ratios. Conclusion Japanese patients receiving HD have lower bone turnover than their European counterparts, even at similar PTH levels. The rationale for the current regional differences in PTH treatment targets remains obscure and deserves further attention.