Bisphosphonate Use in Acute Spinal Cord Injury: A Focused Systematic Review on Zoledronic Acid

Spinal cord injury (SCI) causes significant bone loss as a long-term complication, increasing fracture risk and healthcare costs. Bisphosphonates are widely studied for mitigating bone loss since they can prevent fractures and preserve rehabilitation potential in acute SCI patients. Zoledronic acid, in particular, stands out due to its high potency, dosing convenience, and better patient adherence. This review aims to evaluate the efficacy of bisphosphonates, particularly zoledronic acid, in mitigating bone loss in acute SCI. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines using PubMed, ScienceDirect, PubMed Central (PMC), Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies from January 1, 2016, to December 31, 2024, on bisphosphonate use within six months of SCI were included. Randomized controlled trials using zoledronic acid as the intervention and meta-analyses or systematic reviews covering all bisphosphonates were selected based on predefined inclusion and exclusion criteria. Eight studies, comprising three meta-analyses and five randomized controlled trials with 729 participants, were selected after quality assessment using Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) and a revised Cochrane risk of bias tool for randomized trials (RoB 2). Seven studies demonstrated significant bone mineral density (BMD) improvements at the total hip, four at the lumbar spine, two at the trochanter, and five at the femoral neck. Two meta-analyses performed subgroup analyses of zoledronic acid, demonstrating substantial bone loss reduction, although comparisons with other bisphosphonates were lacking. Reductions in bone resorption markers, such as C-terminal telopeptide (CTX), were observed in five studies. While zoledronic acid exhibits strong anti-resorptive effects and allows for practical intravenous administration, its limited impact on bone formation markers, such as P1NP, and inconsistent BMD improvements across skeletal sites require further investigation. Future studies should assess long-term outcomes, utilize advanced imaging techniques, and directly compare zoledronic acid with other bisphosphonates.