Meta-Analysis
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Sep 18, 2024; 12(3): 97256
Published online Sep 18, 2024. doi: 10.13105/wjma.v12.i3.97256
Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and meta-analysis
Abdul Hannan Siddiqui, Misbah Shaikh, Afia Salman, Muhammad Ahmed Ali Fahim, Fizzah Batool, Tahreem Mari, Sarah Musani, Muneeb Fareed, Rooma Rehan, Amna Hassni, Urooj Nizami, Ayesha Amir, Abdul Moeed, Salim R Surani
Abdul Hannan Siddiqui, Misbah Shaikh, Afia Salman, Muhammad Ahmed Ali Fahim, Fizzah Batool, Tahreem Mari, Sarah Musani, Muneeb Fareed, Rooma Rehan, Amna Hassni, Urooj Nizami, Ayesha Amir, Abdul Moeed, Department of Internal Medicine, Dow University of Health Sciences, Karachi 74200, Sindh, Pakistan
Salim R Surani, Department of Medicine & Pharmacology, Texas A&M University, College Station, TX 77843, United States
Author contributions: Moeed A, Siddiqui AH, Fahim MAA, Salman A, and Surani SR participated in the conceptualization, data curation, investigation, methodology, project administration, resources, supervision, validation, visualization, and writing of the original draft; Shaikh M, Batool F, Mari T, Musani S, Fareed M, Rehan R, Hassni A, Nizami U, and Amir A were involved in project administration and writing of the original draft; Fahim MAA, Moeed A, Siddiqui AH, and Surani SR were involved in the formal analysis, project administration, supervision, validation, visualization, and writing, reviewing, and editing; All authors read and approved the final manuscript.
Conflict-of-interest statement: None of the authors have conflicts of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abdul Moeed, Doctor, MBBS, Academic Editor, Doctor, Researcher, Department of Internal Medicine, Dow University of Health Sciences, Dow Medical College, Karachi 74200, Sindh, Pakistan. abdul.moeed19@dmc.duhs.edu.pk
Received: May 27, 2024
Revised: August 20, 2024
Accepted: August 26, 2024
Published online: September 18, 2024
Processing time: 108 Days and 15.6 Hours
Abstract
BACKGROUND

Denosumab inhibits the receptor activator of nuclear factor kappa-ligand. It markedly increases bone mineral density and has been proven to reduce the risk of fractures. However, numerous adverse effects, notably hypocalcemia, are prevalent in patients with end-stage renal disease (ESRD).

AIM

To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.

METHODS

We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Scopus, Cochrane Central, and EMBASE were systematically searched from inception through March 2024. All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted. The primary outcomes of our study were the incidence of mild, severe, and very severe hypocalcemia. Secondary outcomes included serum levels of intact parathyroid hormone, calcium, and phosphate. The results were pooled and analyzed using a random-effects model.

RESULTS

Seven articles comprising 3240 patients were included in our study. Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia [risk ratio (RR): 2.79; 95% confidence interval (CI): 0.99-7.91; P = 0.05; I² = 37%] and of very severe hypocalcemia (RR: 9.58; 95%CI: 1.58-57.98; P = 0.01; I² = 49%). However, an increase in the occurrence of severe hypocalcemia was non-significant (RR: 4.23; 95%CI: 0.47-38.34; P = 0.20; I² = 96%). Alternatively, denosumab showed a significant decrease in serum intact parathyroid hormone [mean difference (MD): -433.20, 95%CI: -775.12 to -91.28, I2 = 98%, P= 0.01], while there was a non-significant decrease in phosphate (MD: -0.47, 95%CI: -1.35 to 0.41, I2 = 88%, P = 0.30) and calcium levels (MD: -0.33, 95%CI: -0.95 to 0.29, I2 = 94%, P = 0.29).

CONCLUSION

Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.

Keywords: Denosumab; End-stage renal disease; Hypocalcemia; Parathyroid hormone; Dialysis

Core Tip: Denosumab is a monoclonal antibody that inhibits receptor activator of nuclear factor kappa-Β-ligand and prevents bone resorption, making it useful for treating osteoporosis. Although denosumab has an acceptable safety profile, it is known to cause hypocalcemia in patients with renal insufficiency making it contraindicated in patients with hypocalcemia. Such patients may experience muscle and joint pain. To date, very few randomized controlled trials have explored the safety of this drug in patients with end-stage renal disease or on dialysis. This meta-analysis thus appraised the safety profile of denosumab in patients with end-stage renal disease.