Bisphosphonates reduce vertebral fracture risk in multiple myeloma, spinal cord compression effect unclear

BACKGROUND CONTEXT: Bone disease in patients with multiple myeloma (MM) is associated with vertebral complications, which include vertebral fractures and spinal cord compression (SCC). Bone-modifying agents (BMAs), namely bisphosphonates and denosumab, are recommended to reduce skeletal-related events in MM, yet their efficacy in preventing vertebral fractures and SCC remains unclear. PURPOSE: To determine the efficacy of bone-modifying agents (BMAs) in reducing the risk for vertebral fractures and SCC in adults with MM. STUDY DESIGN: Systematic review and meta-analysis following PRISMA guidelines. METHODS: A systematic search of PubMed, Embase, and Web of Science databases was performed on July 11, 2024. Risk of bias, reporting bias, and evidence certainty were evaluated using the RoB 2 tool, funnel plot and Egger's test, and the GRADE approach, respectively. Relevant data were extracted and pooled for pairwise and network meta-analysis. RESULTS: After removing duplicates, 1,354 studies were screened, 108 full-text studies were reviewed for inclusion, and 11 randomized trials were included in the analysis. Compared to no treatment or placebo, lower-potency bisphosphonates were associated with a reduction in the risk for vertebral fractures, with a pooled RR of 0.72 (95% CI: 0.61-0.85, p=.0001), suggesting a 28% reduction in risk. Zoledronate was the most efficacious bisphosphonate in the network meta-analysis, with a 64% reduction in vertebral fracture risk compared to no treatment or placebo (RR=0.36, 95% CI: 0.16-0.77, p=.009). None of the included studies reported the clinical significance of these vertebral complications, and no studies that investigated denosumab met inclusion criteria. Meta-analysis for the SCC outcome was inconclusive due to limited evidence. CONCLUSIONS: The body of literature indicates that bisphosphonates, particularly zoledronate, significantly reduce the risk for vertebral fractures in patients with MM, at least in trial conditions. Additional evidence is necessary to evaluate the real-world clinical impact of these findings, clarify the effects on risk for SCC, and investigate denosumab.