Trends in serum phosphate, calcium, and parathyroid hormone levels according to renal function following denosumab

Abstract

Denosumab affects calcium and phosphate metabolism, especially in chronic kidney disease (CKD). This study found transient calcium and phosphate reductions with parathyroid hormone (PTH) elevation, peaking at 1-3 months, especially in CKD. Levels were normalized by six months. Early monitoring and supplementation are crucial to prevent severe hypocalcemia and excessive PTH rise in CKD patients. Background: Denosumab is widely used for treating osteoporosis but significantly affects calcium and phosphate metabolism. Its impact on these parameters in CKD patients remains unclear. Methods: This retrospective observational study analyzed data from three Korean hospitals, including patients treated with denosumab between November 2016 and December 2021. We assessed the mean percentage change in serum phosphate, calcium, and PTH levels from baseline to 6 months post-treatment. Among the 11,586 patients, 10,069 had normal kidney function, while 1517 had CKD. Results: Serum phosphate levels decline temporarily but returned to baseline within six months, with no significant difference between CKD and normal groups. Serum calcium levels decline more significantly (- 6.48% vs. - 3.42%, p < 0.001) and PTH levels increase in CKD patients (200.84% vs. 124.34%, p < 0.001), especially in 1-3 months. However, calcium and PTH levels also returned to baseline by six months (- 0.76% vs. - 0.67%, p = 0.650; 24.49% vs. 20.78%, p = 0.528). Notably, hypocalcemia was more prevalent in the CKD group than in those with normal kidney function. Conclusion: This study suggests that denosumab induces a transient decrease in serum calcium and phosphate levels, accompanied by a significant increase in PTH levels, particularly during the first 1 to 3 months. Therefore, early-phase monitoring and adequate calcium and vitamin D supplementation are crucial in CKD patients to prevent severe hypocalcemia and excessive PTH elevation. Despite initial fluctuation, denosumab might be a safe treatment option for CKD patients with appropriate monitoring and management.