Reducing the risk of denosumab-induced hypocalcemia in patients with advanced chronic kidney disease: a quality improvement initiative

Denosumab can improve bone health in advanced kidney disease (CKD) but is associated with hypocalcemia. We created a clinical care pathway focused on the safe provision of denosumab in advanced CKD that reduced the risk of hypocalcemia by 37% at our hospital. Similar pathways could be adopted and tested in other centers.

There is an increased risk of hypocalcemia with denosumab in advanced chronic kidney disease (CKD). We aimed to reduce the proportion of patients with advanced CKD who experienced denosumab-induced hypocalcemia at our center.

We conducted a quality improvement (QI) project of patients with CKD stage 3b or less (i.e., estimated glomerular filtration rate <45 mL/min/1.73m² including dialysis) who were part of the Osteoporosis and Bone Disease Program at St. Joseph’s Health Care London (Canada) between December 2020 and January 2023. Our intervention was a clinical care pathway which optimized CKD mineral and bone disorder (CKD-MBD) and 25-hydroxyvitamin levels; provided calcium and vitamin D prophylaxis; promoted multidisciplinary communication between bone and kidney specialists; and carefully monitored calcium post-denosumab injection. Our primary outcome measure was the proportion of patients with hypocalcemia (defined by albumin-corrected serum calcium <1.9mmol/L) at 60 days. Process measures included the appropriate provision of calcium and vitamin D prophylaxis. Balance measures included the development of hypercalcemia and hyperphosphatemia following prophylaxis. We used plan-do-see-act cycles to study four tests of change and presented results using descriptive statistics and run charts.

There were 6 patients with advanced CKD treated with denosumab prior to the implementation of our care pathway (March 2015–October 2020; 83% receiving dialysis). At the time of their denosumab injection, 83% were using 500–1000 mg of calcium, and 83% used 1000–2000 IU of vitamin D₃. Fifty percent developed denosumab-induced hypocalcemia. Following the implementation of our care pathway, 15 patients (40% receiving dialysis) were treated with denosumab. Ninety-three percent received calcium at a daily dose of 350 to 2250 mg and 87% received 1000–2000 IU of vitamin D₃. Thirteen percent developed denosumab-induced hypocalcemia. There was no hypercalcemia or hyperphosphatemia.

A clinical care pathway focused on the safe provision of denosumab in advanced CKD reduced the risk of hypocalcemia in patients treated in our hospital. Similar pathways could be adopted and tested in other centers.