Abstract: PO0581
The Incidence of Hypocalcemia After Denosumab Administration in Patients with CKD
Session Information
- Bone and Mineral Metabolism: Clinical
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Cowan, Andrea, London Health Sciences Centre, London, Ontario, Canada
- Jeyakumar, Nivethika, ICES, Toronto, Ontario, Canada
- Ouédraogo, Alexandra M., ICES, Toronto, Ontario, Canada
- Garg, Amit X., ICES, Toronto, Ontario, Canada
- Karp, Igor, Western University, London, Ontario, Canada
- Khan, Tayyab Sami, London Health Sciences Centre, London, Ontario, Canada
- Silver, Samuel A., Kingston Health Sciences Centre, Kingston, Ontario, Canada
- Thain, Jenny, London Health Sciences Centre, London, Ontario, Canada
- Muanda, Flory Tsobo, ICES, Toronto, Ontario, Canada
- Weir, Matthew A., London Health Sciences Centre, London, Ontario, Canada
- Clemens, Kristin, St Joseph's Healthcare London, London, Ontario, Canada
Background
Patients with chronic kidney disease (CKD) are at increased risk of fragility fracture and its complications. Denosumab is an antiresorptive agent approved for use in CKD, but has been associated with hypocalcemia in those with advanced disease although the incidence is unclear. We examine the real-world incidence of hypocalcaemia in patients with CKD newly prescribed denosumab.
Methods
Using linked healthcare databases (ICES), we conducted a population-based cohort study of adults >65 years newly prescribed denosumab or bisphosphonates from 2012-2017 in Ontario, Canada. We captured the incidence of hypocalcaemia within 180 days of drug dispensing, stratified by eGFR.
Results
We identified 9,319 new users of denosumab and 9,052 new users of oral bisphosphonates. Compared with bisphosphonate users, denosumab users were older (78.8 vs 75.0 years), more often from long-term care, had a history of fragility fracture, and had more advanced CKD.
Approximately one third of patients dispensed denosumab had a calcium level checked within 180 days of their prescription. The risk of hypocalcemia (<2.00mmol/L) with denosumab was low (0.74% 95% CI 0.58-0.93). One third of those had a calcium <1.8mmol/L (0.28% 95% CI (0.19-0.41). The risk of hypocalcemia increased substantially in those with eGFR <30 (8.4% [95% CI 5.5-12.0]). In new users of bisphosphonates, the risk of hypocalcemia was low across all eGFR groups.
Conclusion
In the largest population-based cohort of denosumab users with CKD to date, we found a modest increase in the risk of hypocalcemia with denosumab in those with stage 4 and 5 CKD. These rates are lower than reported in smaller cohort studies. This study was limited by the low numbers of patients with end stage renal disease. Our study emphasizes the importance of awareness of denosumab-induced hypocalcemia, routine monitoring post-denosumab, and benefit-risk assessment before prescribing this treatment to patients with kidney disease.
The cumulative incidence of mild hypocalcemia (Ca <2.00 mmol/L) at 180 days
| eGFR Category (mean GFR ml/min/1.73m2 [SD]) | Denosumab % (95%CI) | Bisphosphonate % (95%CI) |
| All | 0.74 (0.58-0.93) | 0.38 (0.27-0.52) |
| eGFR ≥60 (80 [10.4]) | 0.46 (0.32-0.65) | 0.32 (0.21-0.47) |
| eGFR 30 - <60 (49 [8.1]) | 0.65 (0.39-1.03) | 0.52 (0.27-0.93) |
| eGFR <30 or chronic dialysis (23 [6.0]) | 8.39 (5.49-12.06) | 1.33 (0.26-4.35 |
Funding
- Private Foundation Support