Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I(2) = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.