Efficacy and Safety of Percutaneous Kyphoplasty Combined With Zoledronic Acid for Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis

Osteoporotic vertebral compression fractures (OVCFs) are a significant source of pain and disability among the elderly. While percutaneous kyphoplasty (PKP) offers mechanical stabilization and pain relief, it does not address the underlying bone fragility. Zoledronic acid (ZOL), a strong bisphosphonate, makes bones stronger and may stop them from breaking again. This meta-analysis assessed the efficacy and safety of combining PKP with ZOL versus PKP alone in patients with OVCFs. A systematic search of PubMed, Cochrane Library, and Clinicaltrials.gov was performed up to August 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing PKP plus ZOL versus PKP alone were included. Data were pooled using Review Manager (RevMan) version 5.4 (The Cochrane Collaboration, London, England, UK). Mean difference (MD) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Five RCTs involving 997 patients (499 PKP + ZOL; 498 PKP) were analyzed. The combination therapy showed greater pain reduction (visual analog scale (VAS): MD = -1.18 (-2.04, -0.31)), improved function (Oswestry Disability Index (ODI): MD = -9.18 (-21.57, 3.20)), and increased Cobb angle correction (MD = 1.88 (0.14, 3.63)). Bone mineral density (BMD) improved significantly (MD = 0.08 (0.06, 0.11)), while bone turnover markers (procollagen type I N-terminal propeptide (PINP), β-C-terminal telopeptide (β-CTX), and N-terminal mid-fragment of osteocalcin (N-MID osteocalcin)) were markedly reduced. Adverse events were more common with ZOL (RR = 5.46 (3.75, 7.96)) but were mild and transient. In OVCF patients, combining PKP with ZOL gives better clinical, functional, and bone-strengthening advantages than PKP alone. Even while small side effects happen more often, the treatment is still safe and well-tolerated. This combined method works well to fix both the mechanical stability and the metabolic fragility of osteoporotic fractures.