Impact of Vitamin D Replacement on the Vitamin D–Leptin–Prolidase Axis in Secondary Hyperparathyroidism

Severe vitamin D deficiency commonly results in secondary hyperparathyroidism and increased bone turnover. Despite the well-established inverse relationship between vitamin D and parathyroid hormone, the impact of vitamin D repletion on collagen matrix remodeling and adipose–bone signaling remains unclear, and the combined response of prolidase and leptin has not been previously examined. This prospective observational study included 36 female patients with severe vitamin D deficiency and secondary hyperparathyroidism who received oral vitamin D supplementation (50,000 IU/wk) for 8 weeks. Serum 25-hydroxyvitamin D, parathyroid hormone, alkaline phosphatase, prolidase activity, and leptin levels were assessed before and after treatment, and correlations among biochemical changes were analyzed. Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D levels and reduced parathyroid hormone and alkaline phosphatase concentrations (all p<0.001). Serum prolidase activity increased significantly (p=0.027), whereas leptin levels showed a modest, non-significant decrease. Changes in prolidase activity were positively associated with baseline parathyroid hormone levels and inversely related to parathyroid hormone reduction. Post-treatment vitamin D levels demonstrated a modest positive correlation with leptin concentrations (r=0.347 and p=0.045), while no significant associations were observed between changes in vitamin D and prolidase or leptin levels. Vitamin D repletion in patients with severe vitamin D deficiency–related secondary hyperparathyroidism was associated with distinct biochemical responses, with early collagen matrix remodeling reflected by increased prolidase activity and subtler changes in adipose–bone signaling. These findings suggest temporally divergent pathways of skeletal recovery and support prolidase as a potential dynamic marker of early matrix adaptation.