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Case presentation
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A 74-year-old male with a past medical history of severe osteoporosis, chronic obstructive pulmonary disease (COPD), marginal gastric ulcers status-post sleeve gastrectomy, and Crohn’s disease status-post small bowel resection presented to the emergency department due to an acute onset of right shoulder pain. Vital signs revealed a temperature of 37.2°C, blood pressure of 112/61 mmHg, heart rate of 78, respiratory rate of 16, and oxygen saturation of 92% on 1.5 L by nasal cannula, which he used at baseline. Initial laboratory workup revealed severe hypocalcemia at 4.8 mg/dL and hypophosphatemia at 0.8 mg/dL. Upon further history taking, the patient stated that he receives denosumab injections for his severe osteoporosis. The patient denied muscle cramps, spasms, weakness, seizures, facial twitching, lightheadedness, and psychiatric changes. Of note, he had a history of chronic hypocalcemia with a baseline of 7 mg/dL and reported taking daily calcium and vitamin D supplements. His physical examination was unremarkable except for shoulder pain on the passive range of motion. Chvostek and Trousseau signs were both negative. Additional laboratory workup was significant for hyperparathyroidism and normal magnesium, albumin, and vitamin D levels. His arterial blood gas results revealed respiratory acidosis presumed to be due to COPD.
The patient was admitted to the intensive care unit, monitored on cardiac telemetry, and started on IV calcium carbonate in addition to his home calcium and vitamin D oral supplements. Endocrinology was consulted, and calcium levels were trended until normalization. The patient was ultimately discharged on calcium carbonate 1,250 mg by mouth three times per day, calcium-vitamin D gummies by mouth three times per day, cholecalciferol 1,000 international units by mouth two times per day, and calcitriol 0.5 mcg oral capsule four times per day. His serum calcium level at eight months post-discharge has been maintained at roughly 9.5 mg/dL on this regimen, and he has remained asymptomatic throughout.
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Study Author Conclusions
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This case highlights the importance of obtaining a complete medical history, including medication reconciliation, to identify drug-induced metabolic abnormalities. Denosumab is injected only once every six months, and thus patients often overlook and forget to disclose denosumab as one of their home medications. This is especially true for patients on polypharmacy regimens. There are very few documented reports of patients with denosumab-induced hypocalcemia. The patients in the majority of the previously documented cases of denosumab-induced hypocalcemia have had some form of renal impairment, underlying bone or prostatic malignancies, post-menopausal state, and/or vitamin D deficiency.
However, in this case, the patient developed severe hypocalcemia with a past medical history negative for these conditions. This suggests that denosumab-induced hypocalcemia can occur in patients with good renal function, no underlying malignancy, and normal vitamin D levels. Although the current guidelines recommend monitoring calcium levels only in patients with these underlying conditions and other risk factors predisposing to hypocalcemia, calcium levels should be monitored in all patients receiving denosumab.
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