Beyond surgery: a scoping review of pharmaceutical approaches in treating congenital pseudarthrosis of the tibia

Congenital pseudarthrosis of the tibia (CPT) remains one of the challenging conditions, with high rates of nonunion and refracture despite advances in surgical technique. Pharmacologic and biologic adjuncts have been introduced to enhance bone healing, but their role is incompletely defined. This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance and a Population-Concept-Context framework. PubMed, Scopus, Embase, and Web of Science were searched till October 2025 for clinical studies using pharmacologic or biologic agents in CPT. Eligible designs included trials, cohorts, case series, and case reports reporting union-related outcomes. Thirteen studies published between 2006 and 2025 were included. Bone morphogenetic protein 2 (BMP-2) was evaluated in seven studies and BMP-7/OP-1 in three; three of these studies also used bisphosphonates as co-therapy with BMP, while one investigated mesenchymal stromal cell transplantation. Sample sizes ranged from two to 39, with mean follow-up of approximately 2-7 years. Contemporary BMP-2-based cross-union protocols, often combined with bisphosphonates, have reported near-100% union within 3-9 months and markedly reduced refracture rates. Earlier BMP-7 series and single-agent BMP applications produced more modest and variable union rates, while the mesenchymal stem cell pilot demonstrated histologic repair without mechanical union. Complications were infrequent but long-term safety and growth-plate effects remain uncertain. Pharmacologic adjuncts, particularly BMP-2-based cross-union constructs combined with antiresorptive therapy, show promising structural outcomes in CPT. However, the supporting evidence is derived largely from small, specialized case series without robust comparative data, and should, therefore, be interpreted with caution.