Hypocalcaemia and hospitalisation after initiation of bone-modifying agents in dialysis patients

Abstract Background and Hypothesis Bone-modifying agents are associated with hypocalcaemia in dialysis patients, leading to serious adverse consequences. We examined factors associated with all-cause hospitalisation, longitudinal serum calcium trajectories by medication class, and baseline predictors of hypocalcaemia in dialysis patients initiating bone-modifying agents. Methods Using the JMDC hospital database, we identified dialysis patients newly prescribed bisphosphonates, denosumab, teriparatide, or romosozumab. Factors associated with all-cause hospitalisation were examined using Cox regression. Serum calcium trajectories were assessed over 90 days before and after treatment initiation. Factors associated with hypocalcaemia (corrected calcium < 8.0 mg/dL) within 90 days were analysed. Results Among 2 020 patients on dialysis, 1 057 (52.3%) received bisphosphonates; 693 (34.3%), denosumab; 136 (6.7%), teriparatide; and 134 (6.6%), romosozumab. Hospitalisation occurred in 425 patients, and recent hospitalisation and pretreatment lower corrected serum calcium levels were associated with hospitalisation, with no significant differences across medications. Among 374 patients with laboratory data, post-treatment hypocalcaemia occurred in 99 (26.5%). Persistent reductions in serum calcium levels were observed after initiating denosumab or romosozumab. Adjusted odds ratios (OR) for post-treatment hypocalcaemia were 13.4 (6.90–26.1) for denosumab and 8.09 (2.20–29.8) for romosozumab. Pretreatment calcium and parathyroid hormone levels were associated with post-treatment hypocalcaemia (adjusted ORs: 0.29 [0.18, 0.49] and 1.59 [1.05, 2.39], respectively). Conclusion In dialysis patients, denosumab and romosozumab were associated with a higher risk of post-treatment hypocalcaemia than bisphosphonates, and pretreatment lower calcium was associated with hospitalisation. Our findings highlight the importance of optimising parathyroid hormone management and enhancing calcium monitoring when initiating bone-modifying agents.