Long-term outcome following additional rhBMP-7 application in revision surgery of aseptic humeral, femoral, and tibial shaft nonunion

Abstract

BackgroundSurgical revision concepts for the treatment of aseptic humeral, femoral, and tibial diaphyseal nonunion were evaluated. It was analyzed if the range of time to bone healing was shorter, and if clinical and radiological long-term outcome was better following application of additional recombinant human Bone Morphogenetic Protein-7 (rhBMP-7) compared to no additional rhBMP-7 use.MethodsIn a retrospective comparative study between 06/2006 and 05/2013, 112 patients diagnosed with aseptic diaphyseal humerus (22 patients), femur (41 patients), and tibia (49 patients) nonunion were treated using internal fixation and bone graft augmentation. For additional stimulation of bone healing, growth factor rhBMP-7 was locally administered in 62 out of 112 patients. Follow-up studies including clinical and radiological assessment were performed at regular intervals as well as after at least one year following nonunion surgery.ResultsOne hundred and two out of 112 (humerus: 19, femur: 37, tibia: 47) nonunion healed within 12 months after revision surgery without any significant differences between the cohort groups. According to the DASH outcome measure for the humerus (p = 0.679), LEFS for the femur (p = 0.251) and the tibia (p = 0.946) as well as to the SF-12 for all entities, no significant differences between the treatment groups were found.ConclusionsAseptic diaphyseal nonunion in humerus, femur, and tibia healed irrespectively of additional rhBMP-7 application. Moreover, the results of this study suggest that successful nonunion healing can be linked to precise surgical concepts using radical removal of nonunion tissue, stable fixation and restoration of axis, length and torsion, rather than to the additional use of signaling proteins.Trial registrationThis clinical trial was conducted according to ICMJE guidelines as well as to the approval of the National Medical Board (Ethics Committee of the Bavarian State Chamber of Physicians; TRN: 2016-104) and has been retrospectively registered with the German Clinical Trails Register (TRN: DRKS00012652).

RETRACTED ARTICLE: Comparison of bone morphogenetic protein and autologous grafting in the treatment of limb long bone nonunion: a systematic review and meta-analysis

“…Finally, 5 randomized controlled trials (RCTs) [15][16][17][18][19] and 4 nonrandomized controlled trials [20][21][22][23] were included in the systematic review and meta-analysis, most of which were small sample size studies of 30-124 cases, with a total of 655 nonunion cases. These 9 studies [15][16][17][18][19][20][21][22][23] reported on 11 trials as one (Hackl et al [23]) reported 3 clinical trials. The observation group was treated with BMP plus autologous bone in 5 studies, BMP alone in 2 studies, and BMP combined with natural inorganic bone in one study.…”

Insulin-Like Growth Factor-1 as a Possible Alternative to Bone Morphogenetic Protein-7 to Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells in Vitro

“…There is evidence that the application in a clinical setting leads to consolidation of bone defects, even in cases of delayed healing or non-union [ 14 , 15 , 16 ]. However, the clinical results are controversial: While some authors report positive effects of BMP-7 application on bone healing, other studies did not find a positive influence on bone defect consolidation when BMP-7 was used [ 14 , 17 , 18 , 19 , 20 ]. Using the currently available application form of collagen-incorporated BMP-7 applied to the defect site does not guarantee a continuous stimulation of the local cells by long-lasting BMP-7 release [ 21 , 22 ].…”

Bioengineering strategies for bone and cartilage tissue regeneration using growth factors and stem cells

“…BMPs belong to TGF-β family, and BMP-2(Infuse ® , Minneapolis, MN; Crockett, Rogers, Coxon, Hocking, & Helfrich, 2011) and BMP-7 (OP-1 ® , Olympus, MA) are FDA approved for clinical use (Burkus, Heim, Gornet, & Zdeblick, 2003;McKay, Peckham, & Badura, 2007). Hackl et al (2017) used rhBMP-7 for local administration in 62 out of 112 patients diagnosed with aseptic diaphyseal humerus (22 patients), femur (41 patients), and tibia (49 patients) nonunion. The rhPDGF (Augment ® Bone Graft, BioMimetic Therapeutics, TN) is also commercially available and uses β-tricalcium phosphate as the carrier vehicle (McKay et al, 2007) and has used to treat foot, ankle, and distal radius fractures clinically and it is currently under review by the FDA, and is commercially available in the US.…”

“…There is a large amount of preclinical trial information to support the use of BMPs to induce differentiation of stem cells into osteoprogenitor cells or enhance overall osteogenic activity in accelerating bone healing. Hackl et al (2017) used rhBMP-7 for local administration in 62 out of 112 patients diagnosed with aseptic diaphyseal humerus (22 patients), femur (41 patients), and tibia (49 patients) nonunion. White et al (2007) (Aro et al, 2011).…”