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 presents a significant clinical challenge. These patients have a high burden of fractures, but treatment is complicated by chronic kidney disease-mineral and bone disorder. Denosumab, a monoclonal antibody that inhibits osteoclast-mediated bone resorption, is an attractive option because it is not cleared by the kidneys. However, its use in advanced kidney disease is associated with a significant risk of severe hypocalcemia, particularly in patients with high bone turnover and secondary hyperparathyroidism. While this risk is increasingly recognized—prompting a recent FDA Boxed Warning—the full spectrum of downstream complications is less clear. This case report from Japan describes a patient on peritoneal dialysis who developed not only severe hypocalcemia after denosumab, but also acute heart failure with prolonged, possibly irreversible, cardiac dysfunction.

The report 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. Her medical history included secondary hyperparathyroidism, and her lab work confirmed high-turnover bone disease, with an intact parathyroid hormone level of 419 picograms per milliliter and markedly elevated bone turnover markers. Importantly, a baseline echocardiogram showed normal cardiac function, with a left ventricular ejection fraction of 66 percent. Given the diagnosis of high-turnover osteoporosis, she was started on denosumab. To mitigate the risk of hypocalcemia, she was also prescribed prophylactic active vitamin D analogs and high-dose calcium carbonate, and she was adherent to this regimen. Her serum calcium was monitored every one to two weeks after the injection.

About six weeks after receiving her first dose of denosumab, the patient presented to the emergency department with tetany, generalized fatigue, and shortness of breath, which had made it difficult for her to perform her peritoneal dialysis exchanges. Her laboratory results were striking. Her albumin-corrected serum calcium had plummeted to 6.5 milligrams per deciliter, and an electrocardiogram showed QT prolongation. An echocardiogram revealed a dramatic decline in cardiac function, with an estimated ejection fraction between 30 and 40 percent. She was diagnosed with decompensated heart failure secondary to severe hypocalcemia.

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 correct her calcium levels and manage fluid overload. A coronary angiogram showed no significant stenosis, pointing away from ischemic heart disease as the cause of her heart failure. Over three weeks, her serum calcium normalized and her heart failure symptoms stabilized, allowing for her discharge.

However, the key finding of this case lies in the long-term follow-up. While the denosumab was effective for its intended purpose—her bone mineral density showed significant improvement in the months following the event—her cardiac function did not recover to baseline. Three months after discharge, her ejection fraction had only improved to 43 percent. At a six-month follow-up, it had actually decreased slightly to 36 percent. This persistent cardiac dysfunction, despite the correction of her serum calcium, suggests that the severe hypocalcemic insult may have caused prolonged or even irreversible myocardial injury.

The primary strength of this report is its detailed, long-term clinical and echocardiographic follow-up, which highlights a severe and persistent complication beyond the acute hypocalcemia itself. It serves as a powerful cautionary tale in a specific and vulnerable population—patients on peritoneal dialysis, for whom data on denosumab use are particularly scarce. The main limitation, inherent to any case report, is that we cannot determine causality or estimate the frequency of such an event. It is a single patient's experience, and other factors could have contributed to her heart failure. However, the clear temporal relationship between the denosumab administration, the onset of severe hypocalcemia, and the acute drop in ejection fraction provides a strong signal.

The authors connect their findings to existing literature, noting that while hypocalcemia-induced cardiomyopathy is known to be reversible in many cases, recovery can take months, and some studies suggest that persistent hypocalcemia can lead to irreversible structural changes in the myocardium. This case raises the troubling possibility that even with prompt correction of serum calcium, the cardiac damage may not be fully reversible in some patients.

So, what is the clinical bottom line? This case reinforces the need for extreme caution when considering denosumab for patients with advanced chronic kidney disease, especially those on dialysis with evidence of high bone turnover. The risk of severe, life-threatening hypocalcemia is real, as underscored by the 2024 FDA Boxed Warning. This report adds a critical dimension to that risk: the potential for inducing acute heart failure with prolonged, and possibly incomplete, recovery of cardiac function.

For clinicians, this means the risk-benefit calculation for denosumab in this population must be highly individualized. Prophylactic calcium and vitamin D supplementation are essential but, as this case demonstrates, may not be sufficient to prevent severe hypocalcemia. If denosumab is used, very close monitoring of serum calcium is mandatory, starting as early as one to two weeks after administration. Finally, this case suggests that any patient on denosumab who develops symptoms of hypocalcemia should also be evaluated for cardiac dysfunction, and if heart failure is diagnosed, clinicians should be aware that myocardial recovery may be a prolonged process.

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