Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety

Aquila Gopaul; Tharsan Kanagalingam; Jenny Thain; Tayyab Khan; Andrea Cowan; Nabil Sultan; Kristin K Clemens

doi:10.1007/s11657-021-00971-0

Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety

Arch Osteoporos. 2021 Jul 28;16(1):116. doi: 10.1007/s11657-021-00971-0.

Authors

Aquila Gopaul¹, Tharsan Kanagalingam², Jenny Thain³, Tayyab Khan^{4

5}, Andrea Cowan², Nabil Sultan^{6

7}, Kristin K Clemens^{8

9

10

11

12}

Affiliations

¹ Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Division of Geriatrics, Western University, London, ON, Canada.
⁴ Division of Endocrinology and Metabolism, Western University, London, ON, Canada.
⁵ St. Joseph's Health Care London, London, ON, Canada.
⁶ Division of Nephrology, Western University, London, ON, Canada.
⁷ London Health Sciences Centre, London, ON, Canada.
⁸ Division of Endocrinology and Metabolism, Western University, London, ON, Canada. kristin.clemens@sjhc.london.on.ca.
⁹ St. Joseph's Health Care London, London, ON, Canada. kristin.clemens@sjhc.london.on.ca.
¹⁰ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. kristin.clemens@sjhc.london.on.ca.
¹¹ Lawson Health Research Institute, London, ON, Canada. kristin.clemens@sjhc.london.on.ca.
¹² ICES, Ontario, Canada. kristin.clemens@sjhc.london.on.ca.

PMID: 34319515
DOI: 10.1007/s11657-021-00971-0

Abstract

People with chronic kidney disease (CKD) are at high risk of bone fractures. In this review, we summarize the complexity of fracture prevention in CKD, describe the usefulness of a medication called denosumab, and review its safety in this population. Our article will help doctors manage brittle bones in CKD and encourage researchers to conduct more studies to improve bone health in CKD.

Purpose: Patients with CKD are at increased risk of fragility fractures and associated consequences. We discuss the complexity of fracture prevention in CKD, summarize the efficacy and safety of denosumab, and provide an approach to denosumab-induced hypocalcemia.

Methods: Using predefined terms, we searched PubMed, MEDLINE, and Google Scholar for studies on fracture prevention in CKD and the efficacy and safety of denosumab. We included observational studies, randomized controlled trials (RCTs), meta-analyses, evidence-based reviews, and clinical practice guidelines.

Results: The diagnosis of osteoporosis and prevention of related fragility fractures is complex in CKD, particularly in those with advanced and end-staged kidney disease (ESKD). Prior to initiating denosumab, it is important to assess for and optimize CKD-mineral and bone disorders (CKD-MBD). In observational studies and small RCTs, denosumab has been shown to improve bone mineral density and reduce bone turnover in CKD, but there have been no studies focused upon its fracture efficacy. Denosumab-induced hypocalcemia has also been reported, which disproportionately impacts those with ESKD. Risk factors for hypocalcemia with denosumab use in CKD include lower baseline serum calcium and 25 hydroxyvitamin D and both low and high bone turnover. Choosing the "right patient" for denosumab, supplementing with calcium and vitamin D, adjusting calcium dialysate, and close clinical monitoring are essential if considering this drug.

Conclusion: With optimization of CKD-MBD, calcium and vitamin D supplementation, and close monitoring, denosumab can be considered in CKD. There are however opportunities to better understand its fracture efficacy and safety in an RCT setting.

Keywords: Denosumab; Fracture; Hypocalcemia; Kidney; Osteoporosis; Safety.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Bone Density
Bone Density Conservation Agents* / adverse effects
Denosumab / adverse effects
Humans
Osteoporosis* / drug therapy
Renal Insufficiency, Chronic* / drug therapy
Treatment Outcome

Substances

Bone Density Conservation Agents
Denosumab