Zoledronic Acid Versus Denosumab for Prevention of Spinal Cord Compression in Advanced Cancers With Spine Metastasis: A Meta-Analysis of Randomized Controlled Trials

Abstract

Study Design: Meta-analysis of randomized controlled trials (RCTs). Objectives: The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of spinal cord compression in patients with spine metastases from advanced cancers, by evaluating all available RCTs on this subject. Methods: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of spinal cord compressions in spine metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were spinal cord compression. Results: Three RCTs (5274 patients) were included. Denosumab was not significantly superior to ZA in reducing the likelihood of spinal cord compression, when all tumor types were combined (odds ratio [OR] 0.92, 95% confidence interval [CI; 0.66, 1.28], P = .66). Denosumab was not significantly favored over ZA in endodermal origin (breast and prostate; OR 0.72, 95% CI [0.43, 1.19], P = .20) and mesodermal origin tumors (solid tumors and multiple myeloma; OR 1.10, 95% CI [0.72, 1.69], P = .66). Conclusion: Denosumab does not significantly reduce the likelihood of spinal cord compressions in comparison to ZA in patients with spine metastases. When spinal cord compressions were grouped by tumor origin (endodermal or mesodermal), there remained no significant difference between denosumab and ZA. Further long-term studies are needed to determine the effectiveness of these treatment regimens.

The use of osteoclast inhibitors in metastatic breast cancer

“…Bisphosphonates do not alter spinal cord compression odds ratio (OR 0.71, confidence interval CI 95%, 0.47-1.08, p value = 0.113) and denosumab use was shown to decrease it, but not significantly (OR 0.92, CI 95%, 0.66-1.28, p = 0.66). Overall, denosumab was not found to be significantly superior to zoledronic acid in decreasing spinal cord compression risk in metastatic breast cancer to the bone [18,19].…”

Spinal metastasis: narrative reviews of the current evidence and treatment modalities

“… 39 , 40 Denosumab has shown no superiority in reducing the incidence of spinal cord compression compared with zoledronic acid. 41 Denosumab also demonstrated a lower incidence of renal toxicity and acute phase reactions such as fever. 38 However, denosumab treatment is associated with a higher risk of hypocalcaemia and osteonecrosis of the jaw.…”

“…[35][36][37] Denosumab, a human monoclonal antibody that inhibits the receptor activator of nuclear factor kappa-B ligand, provides an alternative to zoledronic acid for SRE prevention. [38][39][40][41] It is administered at a dose of 120 mg subcutaneously every 4 weeks. 38 Compared with zoledronic acid, denosumab is superior in delaying the occurrence of first and subsequent SREs in solid tumours and multiple myeloma.…”

Holistic Approach to the Diagnosis and Treatment of Patients with Tumor Metastases to the Spine

“…In these cases, Denosumab, a human monoclonal antibody that strongly binds the receptor activator for Nuclear Factor κ B Ligand (RANKL), has comparable effectiveness to zoledronic acid (ZA), thus inhibiting osteoclast maturation and bone tissue resorption, which is great importance in the prevention of compression of the spinal cord, bone tissue destroyed by cancer. It is subcutaneously administered at a dose of 120 mg every 4 weeks [ 94 ].…”