Phosphate handling as a determinant of osteoporosis in primary hyperparathyroidism

Introduction: Primary hyperparathyroidism is characterized by chronic parathyroid hormone excess, leading to hypercalcemia, increased bone turnover, and skeletal complications. Although osteoporosis is a common manifestation of these, the biochemical determinants of bone loss remain insufficiently defined. The roles of active vitamin D and renal phosphate handling require further clarification. This study aimed to identify biochemical determinants of osteoporosis in patients with primary hyperparathyroidism, with a particular focus on the contribution of calcitriol levels and renal phosphate handling. We further sought to evaluate their predictive performance in discriminating osteoporotic from non-osteoporotic individuals. Materials and methods: We retrospectively analyzed 74 adults with primary hyperparathyroidism ineligible for surgery, assessing serum calcium, phosphate, vitamin D metabolites, parathormone, and 24 h urinary calcium. Renal phosphate handling was estimated by TMP/GFR. Logistic regression and ROC analyses identified independent predictors and optimal cutoff values for osteoporosis. Results: Osteoporosis was present in 33.8% of patients. Individuals with osteoporosis demonstrated significantly higher calcitriol levels and lower renal phosphate reabsorption, also in multivariate analysis, while serum calcium, phosphate, and 25-hydroxyvitamin D did not differ between groups. Receiver operating characteristic curve analysis identified clinically meaningful cutoff values for both parameters. Conclusion: Increased levels of the active form of vitamin D and impaired renal conservation of phosphate are independently associated with osteoporosis in primary hyperparathyroidism, outperforming traditional biochemical markers. Incorporating these measures into routine clinical assessment may improve identification of patients at high skeletal risk and enhance decision-making in the management of bone disease in primary hyperparathyroidism.