Supplementary Material



Background: Osteoporosis or cardiovascular disease prevalence increase with age. Osteoporosis medicine's cardiovascular safety should be monitored. We evaluate the cardiovascular effects of antiosteoporosis medications, namely hormone therapies, bisphosphonates, parathyroid hormone analogs, anti-receptor activator of nuclear factor kappa-B ligand, and romosozumab.

Method: We performed a standard, random-effect, pairwise meta-analysis for cardiovascular disease risk to estimate the available direct evidence of each drug class. The literature search was conducted in PubMed, Embase, and on December 31, 2021. Parallel group randomized and controlled trials were eligible if they compared one kind of anti-osteoporosis agents. For every possible pairwise comparison, the association between treatment and outcomes was obtained using odds.

Results: The search yielded 10,162 records. Screening and full-text article analysis identified 77 trials, including 106,982 patients, comparing five classes of anti-osteoporosis drugs and a placebo. Antireceptor activator of nuclear factor kappa-B ligand, revealed a significantly higher risk of cardiovascular disease than placebo (risk ratio 1.25 [95% confidence interval 1.07% to 1.45%]). The Surface Under the Cumulative Ranking confirmed that anti-receptor activator of nuclear factor kappa-B ligand use was most likely to result in cardiovascular disease in patients with osteoporosis; it had a significantly higher risk of coronary artery disease, cerebrovascular disease, angina, and transient ischemic accident (risk ratio 1.26 [95% confidence interval 1.01% to 1.58%]).

Conclusions and Relevance: In this network meta-analysis of clinical trials of patients with osteoporosis, different classes of anti-osteoporosis medications were associated with different effects on cardiovascular events.