Severe symptomatic hypocalcemia and prolonged heart failure after treatment of osteoporosis with denosumab in a peritoneal dialysis patient: A case report

Welcome to AudioScholar. Today we're covering "Severe symptomatic hypocalcemia and prolonged heart failure after treatment of osteoporosis with denosumab in a peritoneal dialysis patient: A case report," by Yoshida K and colleagues, published in Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis.

Managing osteoporosis in patients on dialysis is a significant clinical challenge. These patients have a high risk of fractures, but their treatment is complicated by chronic kidney disease-mineral and bone disorder. Denosumab, a monoclonal antibody that inhibits osteoclast-mediated bone resorption, has emerged as a promising option. Because it isn't cleared by the kidneys, it can be used in patients with advanced renal failure. However, its potent effect on bone turnover also creates a well-known risk of severe hypocalcemia, particularly in patients with pre-existing secondary hyperparathyroidism and high bone turnover. This case report from Japan explores the potential severity of this complication in a peritoneal dialysis patient, highlighting not just the acute electrolyte disturbance but also a prolonged and serious cardiovascular consequence.

The paper details the case of a 70-year-old woman with diabetic nephropathy who had been stable on continuous ambulatory peritoneal dialysis for one year. During a routine checkup, she was diagnosed with osteoporosis based on a T-score of minus 2.5. Her relevant history included secondary hyperparathyroidism, with an intact parathyroid hormone level of 419 picograms per milliliter, well above the upper limit of normal. Critically, her baseline labs also showed very high bone turnover markers, a very low 25-hydroxy vitamin D level of 3.7 nanograms per milliliter, and a baseline corrected calcium on the lower end of normal at 7.6 milligrams per deciliter. Her baseline echocardiogram, however, showed normal cardiac function with an ejection fraction of 66 percent.

Given her diagnosis of high-turnover osteoporosis, she was started on denosumab. In an attempt to prevent the known risk of hypocalcemia, she was also prescribed prophylactic high-dose calcium carbonate and an active vitamin D analog. Her serum calcium levels were monitored every one to two weeks as recommended.

Despite these preventive measures, the patient’s clinical course took a sharp turn. Approximately six weeks after receiving her first dose of denosumab, she presented to the emergency department with tetany, generalized fatigue, and dyspnea. Her lab work confirmed severe hypocalcemia, with an albumin-corrected calcium of 6.5 milligrams per deciliter and associated QT prolongation on her electrocardiogram. An echocardiogram revealed a dramatic decline in cardiac function, with her ejection fraction plummeting from 66 percent at baseline to between 30 and 40 percent. She was diagnosed with decompensated heart failure, triggered by the severe hypocalcemia against a backdrop of mild fluid overload.

The patient was admitted for urgent management. Her treatment included intravenous calcium gluconate, increased doses of oral calcium and vitamin D, and three sessions of intermittent hemodialysis using a high-calcium dialysate to manage fluid and correct her calcium levels. A coronary angiogram ruled out significant coronary artery disease as a cause for her heart failure. After three weeks of intensive therapy, her calcium levels normalized, her heart failure stabilized, and she was discharged.

The most striking finding of this case, however, was the long-term outcome. While the denosumab was effective for her osteoporosis—her bone mineral density showed marked improvement in the months following the event—her cardiac function did not recover. An echocardiogram three months after discharge showed an ejection fraction of only 43 percent. Six months after the initial event, it had not improved further, measuring just 36 percent. This demonstrates a persistent, prolonged cardiac dysfunction long after the inciting metabolic disturbance was corrected.

The primary strength of this report is its detailed documentation of a severe adverse event in an under-studied population. While the risk of denosumab-induced hypocalcemia in advanced kidney disease is known, data specifically in peritoneal dialysis patients is limited. This case provides a clear, cautionary example of how severe this complication can be. Furthermore, it highlights a crucial secondary consequence: prolonged, and possibly irreversible, heart failure. The authors carefully documented the patient's cardiac function before, during, and for six months after the event, making a strong temporal case for the link between the hypocalcemic episode and the persistent cardiomyopathy.

The major limitation, inherent to any case report, is that it is an observation of a single patient. We cannot determine the incidence of such an event or definitively prove causation from this one case. The patient had multiple comorbidities, including diabetes and peripheral artery disease, which could have contributed to her cardiac outcome. However, the acute and dramatic drop in ejection fraction coinciding precisely with severe hypocalcemia, in the absence of an acute coronary event, strongly suggests the hypocalcemia was the primary trigger for the decompensation and subsequent prolonged dysfunction.

So, what is the clinical bottom line? This case serves as a stark reminder of the serious risks associated with denosumab in patients with advanced chronic kidney disease, particularly those with high-turnover bone disease and secondary hyperparathyroidism. The risk is so significant that in January 2024, the United States Food and Drug Administration issued a Boxed Warning about severe hypocalcemia in this patient population.

For the practicing clinician, this report reinforces several key actions. First, before even considering denosumab for a dialysis patient, a thorough risk assessment is mandatory. This includes checking baseline calcium, phosphorus, parathyroid hormone, and vitamin D levels. This patient's very low vitamin D and high PTH put her in the highest risk category. Second, any pre-existing hypocalcemia or vitamin D deficiency must be aggressively corrected *before* administering the first dose. Third, after administration, vigilant monitoring is essential. Serum calcium should be checked frequently, perhaps even more often than the one-to-two-week interval used in this case, especially during the first month when the calcium nadir typically occurs.

Finally, this case illustrates that the consequences can extend beyond the electrolyte abnormality itself. The potential for prolonged or irreversible cardiac damage adds a new layer of concern. Clinicians must counsel patients about these severe risks. While denosumab remains a potent tool for preventing fractures, its use in dialysis patients requires extreme caution, careful patient selection, and a robust plan for prevention and monitoring of its life-threatening complications.

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