Effect of Bone Morphogenetic Protein-2 in the Treatment of Long Bone Non-Unions

Thomas Fuchs; Josef Stolberg-Stolberg; Philipp A Michel; Patric Garcia; Susanne Amler; Dirk Wähnert; Michael J Raschke

doi:10.3390/jcm10194597

Effect of Bone Morphogenetic Protein-2 in the Treatment of Long Bone Non-Unions

J Clin Med. 2021 Oct 6;10(19):4597. doi: 10.3390/jcm10194597.

Authors

Thomas Fuchs¹, Josef Stolberg-Stolberg², Philipp A Michel², Patric Garcia², Susanne Amler³, Dirk Wähnert⁴, Michael J Raschke²

Affiliations

¹ Clinic for Orthopaedics, Trauma-, Hand- and Reconstructive Surgery, Vivantes Klinikum im Friedrichshain, Landsberger Allee 49, 10249 Berlin, Germany.
² Department of Trauma-, Hand- and Reconstructive Surgery, Albert-Schweitzer-Campus 1, University Hospital Muenster, Building W1, 48149 Muenster, Germany.
³ Institute of Biostatistics and Clinical Research, University of Muenster, Schmeddingstrasse 56, 48149 Muenster, Germany.
⁴ Department of Trauma and Orthopedic Surgery, Protestant Hospital of Bethel Foundation, Campus Bielefeld-Bethel, University Hospital OWL of Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany.

Abstract

Background: Delayed fracture healing continues to cause significant patient morbidity and an economic burden to society. Biological stimulation of non-unions includes application of recombinant bone morphogenetic protein-2 (rhBMP-2). However, rhBMP-2 use continues to be a matter of controversy as literature shows scarce evidence for treatment effectiveness.

Questions: The objective of this study was to evaluate the effectiveness of rhBMP-2 treatment on long bone non-unions measuring union rate and time to union. Furthermore, we assess risk factors for treatment failure.

Methods and patients: A total of 91 patients with non-unions of long bones were treated with rhBMP-2 (n = 72) or standard care without BMP (n = 19) at our institution. Patient characteristics, comorbidities, nicotine consumption, and complications were recorded. Bone healing was assessed by plane X-rays and clinical examination. Patients were followed up with for 24 months.

Results: Overall, there was significantly faster bone healing after rhBMP-2 application compared to the no-BMP group (p < 0.001; HR = 2.78; 95% CI 1.4-5.6). Union rates differed significantly between rhBMP-2 compared to the no-BMP group (89% vs. 47%; p < 0.001). At the humerus, there was neither a significantly higher union rate in the rhBMP-2 (83%) compared to the no-BMP group (50%) (p = 0.26; n = 12) nor a faster bone healing with a median time of 9 months in both groups (HR = 2.01; 95% CI 0.49-8.61; p = 0.315). The 33 femora treated using rhBMP-2 healed significantly faster than 9 femora in the no-BMP group (HR = 2.93; 95% CI 1.00-8.4; p = 0.023) with significant differences in union rate with 85% and 44%, respectively (p = 0.022). Regarding tibia non-unions, 25 out of 27 (93%) healed with a median of 9 months after rhBMP-2 application with no significant difference in the no-BMP group (33%) in time to union (p = 0.097) but a significantly higher union rate (p = 0.039). There was no effect of comorbidities, age, sex, soft tissue damage, or nicotine use on time to union, union rate, or secondary interventions.

Conclusion: Consistent with the literature, overall, significantly higher union rates with reduced time to union were achieved after rhBMP-2 application. Femoral and tibial non-unions in particular seem to profit from rhBMP-2 application.

Keywords: bone healing; bone morphogenetic protein; fracture; long bone non-union; pseudarthrosis.