Bone pain and pruritus mediate parathyroidectomy-induced sleep improvement in secondary hyperparathyroidism: A temporal pathway analysis of a dual-center longitudinal cohort.

Abstract

Severe sleep disturbances are highly prevalent in secondary hyperparathyroidism. While parathyroidectomy corrects biochemical abnormalities, longitudinal evidence elucidating mechanisms driving sleep improvement remains scarce. A total of 443 secondary hyperparathyroidism patients undergoing parathyroidectomy from 2 independent centers were enrolled. Biochemical parameters, bone pain/pruritus (visual analog scale), and sleep quality (Pittsburgh Sleep Quality Index) were longitudinally assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Linear mixed-effects models characterized sleep trajectories. Temporal cascaded parallel mediation models were constructed to test the sequence: 1-week parathyroid hormone → 1-month symptoms → 3-month sleep. Baseline sleep disturbance rates were 73.6% and 78.2% across cohorts. Postoperatively, sleep quality exhibited stepwise improvement, with 3-month Pittsburgh Sleep Quality Index scores significantly decreasing by 7.19 and 8.08 points, respectively (both P < .001). Structural equation modeling demonstrated that the direct effect of 1-week parathyroid hormone decline on 3-month sleep was nonsignificant. Instead, indirect pathways via alleviated bone pain and pruritus were highly significant, indicating that sleep improvement was predominantly mediated by symptom relief rather than a direct hormonal effect. This pattern remained consistent across unadjusted and fully adjusted models. In this 3-month observational study, postparathyroidectomy sleep improvement is not primarily driven by a direct effect of parathyroid hormone reduction but is predominantly mediated by a temporal pathway: biochemical correction → symptom relief (bone pain and pruritus) → sleep improvement.