MON-796 - Denosumab-Associated Hypocalcemia in Advanced Chronic Kidney Disease: A Case of Reduced Magnitude with Subsequent Dosing

Background: Denosumab is an effective and convenient treatment for osteoporosis in patients with advanced chronic kidney (CKD), given that it is not renally excreted and thus dose adjustments based on GFR are typically not required. Compared with patients who have normal or mildly impaired renal function, patients with advanced CKD are at increased risk of severe hypocalcemia (Ca < 7.5 mg/dL) that generally occurs 2-10 weeks following administration. Emerging evidence suggests that this risk may be highest after initial dose, and lower with subsequent injections.

Clinical

Case: We present a case of a 77-year-old male with CKD Stage IV (eGFR: 17) who was diagnosed with osteoporosis at age 76 via dual-energy X-ray absorptiometry (DEXA) (left forearm and left hip T score < 2.5). Denosumab 60 mg subcutaneous injections every 6 months was initiated for treatment. Following the initial injection in 5/2025, the patient developed severe hypocalcemia within one week (serum calcium 6.4 mg/dL, ionized calcium 0.8 mmol/L), requiring initiation of calcitriol 0.25 mcg daily (which was over time increased to 0.25 mcg twice daily) and oral calcium carbonate (up to 1 g twice daily). Serum calcium levels fluctuated over the following weeks, requiring multiple dose adjustments and intermittent re-initiation of calcium supplementation. Gradual stabilization of calcium level was achieved over approximately 2.5 months, after which calcium carbonate and calcitriol were successfully discontinued. Upon the patient’s second denosumab injection in 11/2025, low-dose prophylactic calcitriol 0.25 mcg daily and calcium carbonate were initiated. In contrast to the first dose, calcium levels remained stable, allowing for discontinuation of calcitriol within one week and all calcium supplementation within three weeks without recurrence of hypocalcemia.

Conclusion: The risk of hypocalcemia with denosumab therapy in patients with advanced CKD is well documented. The impaired kidney is unable to produce adequate calcitriol to facilitate absorption of calcium from the GI tract, so the body becomes increasingly reliant on calcium mobilization from the bone to maintain calcium homeostasis. Denosumab’s suppression of osteoclast activity leads to reduced skeletal calcium release and thus a higher risk of hypocalcemia in these patients. This effect is most pronounced after the first injection, with attenuated risk following subsequent doses. In our case, the initial denosumab dose caused severe, prolonged hypocalcemia requiring intensive supplementation and monitoring for 2.5 months, whereas after the second dose, calcium level remained stable and calcium supplementation was discontinued within three weeks. Denosumab-associated hypocalcemia in advanced CKD appears greatest after the first dose, emphasizing the need for close biochemical monitoring and frequent calcium and vitamin D dose adjustments.

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