Cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis: A meta-analysis and systematic review

ShuangHua Liu; YiMei Tan; WeiDong Huang; HongSheng Luo; BingCheng Pan; Shuan Wu

doi:10.1016/j.semarthrit.2023.152304

Cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis: A meta-analysis and systematic review

Semin Arthritis Rheum. 2024 Feb:64:152304. doi: 10.1016/j.semarthrit.2023.152304. Epub 2023 Nov 8.

Authors

ShuangHua Liu¹, YiMei Tan², WeiDong Huang², HongSheng Luo², BingCheng Pan³, Shuan Wu⁴

Affiliations

¹ Nanhai Hospital of Traditional Chinese Medicine, Jinan University, No.16, Guicheng South Fifth Road, Foshan, 528200 Guangdong, China; College of Traditional Chinese Medicine, Jinan University, No.601, Huangpu Avenue West, Guangzhou, 510632 Guangdong, China.
² Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200 Guangdong, China.
³ College of Traditional Chinese Medicine, Jinan University, No.601, Huangpu Avenue West, Guangzhou, 510632 Guangdong, China.
⁴ Nanhai Hospital of Traditional Chinese Medicine, Jinan University, No.16, Guicheng South Fifth Road, Foshan, 528200 Guangdong, China; College of Traditional Chinese Medicine, Jinan University, No.601, Huangpu Avenue West, Guangzhou, 510632 Guangdong, China; Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200 Guangdong, China. Electronic address: ShuanWu135@outlook.com.

PMID: 37984227
DOI: 10.1016/j.semarthrit.2023.152304

Abstract

Purpose: Osteoporosis is intimately linked to cardiovascular disease and it has been uncertain that zoledronic acid is not correlated with cardiovascular disease. We intended to assess the cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis.

Methods: We included only randomized controlled trials (RCTs) of patients with osteoporosis receiving zoledronic acid or a placebo. We systematically searched PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, the Chinese National Knowledge Infrastructure, ClinicalTrials.gov, and ICTRP from the time of database creation to April 5, 2023. Two investigators extracted data independently on study characteristics, outcomes of interest, and risk of bias based on PRISMA guidelines.

Results: As of April 5, 2023, our search identified 32,361 records, and after excluding these records, 9 RCTs were included in the meta-analysis. The overall risk ratio for cardiovascular events with zoledronic acid for primary osteoporosis compared with placebo was 1.15 (95 % CI 1.05-1.26, I²=12 %, P = 0.002), while the risk of major adverse cardiovascular events with zoledronic acid (RR 1.03, 95 % CI 0. 89-1.18, I²=21 %, P = 0.71) was not significant, possibly due to atrial fibrillation (RR 1.21, 95 % CI 0.99-1.47, I²=0 %, P = 0.06) versus the increased relative risk of arrhythmia (RR 1.30, 95 % CI 1.11-1.52, I²=34 %, P = 0.001). Overall, the cardiovascular risk of zoledronic acid for the treatment of primary osteoporosis was not significant; however, the relative risk of elevated atrial fibrillation and arrhythmias remains to be further studied.

Conclusions: In women with primary osteoporosis, zoledronic acid may increase the risk of atrial fibrillation (P = 0.06) and arrhythmias (P = 0.001) compared with placebo, independent of the risk of major adverse cardiovascular events, angina, and heart failure. However, the sample size of men with primary osteoporosis is small, and the cardiovascular risk of zoledronic acid in men with osteoporosis is uncertain.

Keywords: Cardiovascular safety; Meta-analysis; Osteoporosis; Zoledronic acid.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Atrial Fibrillation*
Female
Humans
Male
Osteoporosis* / drug therapy
Zoledronic Acid / adverse effects

Substances

Zoledronic Acid