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.