MON-750 Evaluating the Effects of High-Dose Vitamin D Supplementation on Serum Calcium: Insights from a Retrospective Analysis

Abstract Disclosure: B. Chow: None. S. Noguchi: None. G. Singh: None. A. Rajpal: None. K. Mehta: None. A.F. Baqai: None. Background: Vitamin D deficiency is being increasingly recognized, leading many clinicians to prescribe high-dose vitamin D (HDVD). Prolonged use of HDVD however, has been associated with toxicity including hypercalcemia. Given the rising use of HDVD the incidence of HDVD-induced hypercalcemia is likely to increase, however its true prevalence remains unknown. In this study, we aimed to assess the prevalence of HDVD-induced hypercalcemia in a safety-net hospital and to identify baseline characteristics that may increase the risk of hypercalcemia. Methods: We conducted a cohort study at Alameda Health System, a safety-net hospital system in Oakland, California. Using the Slicer Dicer feature in Epic EHR, we identified approximately 122 patients with vitamin D <20mg/ml who were prescribed HDVD (weekly ergocalciferol 50,000 international units or higher) and developed hypercalcemia (serum calcium >10.5 mg/dL) between June 2021 and May 2023. Each patient was queried for age, sex, race and calcium levels before and after HDVD. Pharmacies were queried to confirm that the patient acquired their prescription. Our primary end point was hypercalcemia. Results: The median age was 56.84±15.96 years and 64% identified as female. The racial distribution was 41% African American (AA), 32% Latinx and 22% Asian. Baseline serum calcium was 9.8 mg/dl and median vitamin D was 14 (IQR 13-18). Following HDVD, these values increased to a median of 10.5 mg/dl (9.9-10.7 mg/dl) for serum calcium and 21.5 (IQR 17.5-32) for vitamin D (p<0.001). Baseline vitamin D was lower in AA and Latinx groups compared to others, while baseline serum calcium did not significantly differ across racial groups. Notably, baseline serum calcium (particularly >9.8 mg/dl) emerged as the strongest predictor of hypercalcemia following HDVD. Discussion: Our study highlights the impact of HDVD on calcium levels, particularly in those with higher baseline calcium levels. A baseline calcium >9.8 mg/dL strongly predicts HDVD-induced hypercalcemia, suggesting underlying calcium dysregulation. HDVD may also unmask primary hyperparathyroidism. Furthermore, AA patients showed lower baseline vitamin D levels. As AA patients are known to have lower levels of vitamin D binding protein, total 25-hydroxyvitamin D may underestimate bioavailable vitamin D, increasing the risk of HDVD-induced hypercalcemia. This highlights concerns about relying on total vitamin D levels to guide supplementation decisions in diverse populations. Our findings align with the 2024 Endocrine Society Clinical Practice Guidelines, which favor lower daily dosing over HDVD for vitamin D deficiency. If HDVD is chosen, clinicians should monitor calcium levels before and during HDVD, especially in AA patients and those with high baseline calcium. Future research should refine risk assessment to optimize vitamin D therapy while reducing adverse metabolic outcomes. Presentation: Monday, July 14, 2025