Risk of new vertebral compression fractures and serious adverse effects after vertebroplasty: a systematic, critical review and meta-analysis of randomized controlled trials.

Background: Osteoporotic vertebral fractures (OVFs) significantly impact morbidity, mortality, functionality, and quality of life. Vertebroplasty, a widely utilized treatment for OVFs, has its efficacy and safety debated due to varying outcomes reported across clinical trials and meta-analyses. This study aims to critically review and conduct a meta-analysis of randomized controlled trials (RCTs) focusing on the safety of vertebroplasty, specifically its association with serious adverse effects and the development of new vertebral fractures, while exploring potential confounders.

Methods: We conducted a systematic review and meta-analysis by searching PubMed, Web of Science, and EMBASE. The search was updated to February 23, 2024. We included published RCTs comparing vertebroplasty to conservative treatment (CT) or placebo/active control, focusing on new fractures and serious adverse effects. The primary outcomes were "incidence of new fractures" and "serious adverse effects". We applied the Dersimonian-Laird method with a random effects model to estimate risk ratios (RRs) of the primary outcomes, using the I² statistic to assess heterogeneity among studies. Sensitivity analyses were conducted when significant heterogeneity was detected. Subgroup analyses were performed based on the characteristics of the control groups, risk of bias based on The Cochrane Risk of Bias Tool 2, time from fracture onset, and multicentric versus single-center trials.

Results: In total, 14 RCTs encompassing 1,413 patients were analyzed. High and unclear risk of bias were observed in 15 and 25 items, respectively. No significant difference was observed in the incidence of new vertebral fractures between vertebroplasty and the control groups [RR =1.05, 95% confidence interval (CI): 0.71-1.56; I²=55%; P<0.01]. However, vertebroplasty was associated with a significantly lower incidence of serious adverse effects (RR =0.53, 95% CI: 0.31-0.91; I²=0%; P=0.93). Subgroup analyses revealed no significant differences based on control types, risk of bias, or number of institutions involved. Notably, early vertebroplasty (within 6 weeks of symptom onset) showed a protective effect against new vertebral fractures (RR =0.60, 95% CI: 0.38-0.92; I²=0%; P=0.53). The sensitivity analysis showed that one study influenced the observed heterogeneity but did not significantly modify the pooled estimate.

Conclusions: Vertebroplasty is not associated with an increased risk of developing new vertebral fractures and may reduce the risk of serious adverse effects compared to placebo or CT. Early intervention post-fracture appears beneficial. However, the limited number and quality of RCTs call for further high-quality studies.