Efficacy and safety of Burosumab in tumor-induced osteomalacia: A systematic review and meta-analysis

Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by defective bone mineralization due to excessive fibroblast growth factor 23 production, leading to hypophosphatemia, phosphaturia, and osteomalacia. Burosumab, a monoclonal antibody that targets fibroblast growth factor 23, has emerged as a promising therapeutic option for patients with tumor-induced osteomalacia. This systematic review and meta-analysis assesses the efficacy and safety profile of Burosumab in managing tumor-induced osteomalacia, particularly in cases refractory to conventional treatments or when surgical resection of the tumor is not feasible. This systematic review and meta-analysis adhered to the PRISMA guidelines and the Cochrane Handbook. Eligible studies included clinical trials evaluating Burosumab against placebo or standard care in patients with tumor-induced osteomalacia. Key outcomes encompassed serum phosphate levels, histomorphometric osteoid parameters, worst pain scale scores, and safety endpoints. Data extraction and quality appraisal were undertaken independently by two reviewers. Pooled means and events per 100 observations were derived using an inverse-variance random-effects model. Four studies met the eligibility criteria, encompassing 44 patients treated with Burosumab. Burosumab effectively stabilized serum phosphate levels (MD = 0.99; IC 95% 0.77–1.21; I 2 = 0%). Histomorphometric parameters of osteoid tissue demonstrated marked improvements following Burosumab treatment, including reductions in thickness (MD = −4.56; IC 95% −6.72 to −2.40; I 2 = 29.6%), volume (MD = −5.45; IC 95% −6.91 to −3.99; I 2 = 0%), however, no significant change was observed in surface area (MD = −0.56; IC95% −3.63 - 2.50; I 2 = 0%). Burosumab also significantly reduced pain score (MD = −1.11; IC95% −2.27 - 0.04; I 2 = 0%). Safety analyses revealed that 79.33% (IC 95% 15, 84-98,74; I 2 = 80.7%) of patients experienced adverse events, which were predominantly mild and seldom necessitated treatment discontinuation. Burosumab was associated with improvements in serum phosphate and bone histomorphometric parameters. A trend toward pain reduction was observed. The safety profile appeared acceptable, although adverse events were frequent. Findings should be interpreted considering the limited evidence base. • Burosumab increases serum phosphate in tumor-induced osteomalacia. • Bone histomorphometry suggests improved mineralization. • Pain scores show a trend toward improvement. • Adverse events were frequent but mostly mild.