Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

Papanagiotou, Marianthi; Dailiana, Zoe; Karachalios, Th.; Varitimidis, Sokratis; Hantes, Michael; Dimakopoulos, Georgios; Vlychou, Marianna; Malizos, Konstantinos N.

doi:10.5312/wjo.v8.i1.36

Cited by 16 publications

(13 citation statements)

References 27 publications

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“…No differences concerning elastic fibers or small vessel formation could be observed between the groups. It has been demonstrated by us and others that administration of BMP-7 results in excessive bone formation [45], heterotopic ossification [46] and bone with an abnormal structure and diminished biomechanical properties [47]. This is confirmed by some other studies employing BMP-2.…”

Section: Histological Analysessupporting

confidence: 58%

Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration

Lauer

Wolf

Mehler

et al. 2020

IJMS

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Large segmental bone defects occurring after trauma, bone tumors, infections or revision surgeries are a challenge for surgeons. The aim of our study was to develop a new biomaterial utilizing simple and cheap 3D-printing techniques. A porous polylactide (PLA) cylinder was printed and functionalized with stromal-derived factor 1 (SDF-1) or bone morphogenetic protein 7 (BMP-7) immobilized in collagen type I. Biomechanical testing proved biomechanical stability and the scaffolds were implanted into a 6 mm critical size defect in rat femur. Bone growth was observed via x-ray and after 8 weeks, bone regeneration was analyzed with µCT and histological staining methods. Development of non-unions was detected in the control group with no implant. Implantation of PLA cylinder alone resulted in a slight but not significant osteoconductive effect, which was more pronounced in the group where the PLA cylinder was loaded with collagen type I. Addition of SDF-1 resulted in an osteoinductive effect, with stronger new bone formation. BMP-7 treatment showed the most distinct effect on bone regeneration. However, histological analyses revealed that newly formed bone in the BMP-7 group displayed a holey structure. Our results confirm the osteoinductive character of this 3D-biofabricated cell-free new biomaterial and raise new options for its application in bone tissue regeneration.

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Section: Histological Analysessupporting

confidence: 58%

Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration

Lauer

Wolf

Mehler

et al. 2020

IJMS

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“…Therefore, these authors recommended caution when using rhBMP-7 in the upper extremity in regions with close proximity of soft tissue to bone, and in regions where loss of motion would be problematic. Recently, it was reported that ectopic ossification after the use of rhBMP-7 in nonunion was common but did not compromise the final clinical outcome in most cases, and affected only male patients [46]. Focusing on the structure of the treatment groups in the current study, we were not able to confirm these previous findings, and furthermore, there was no relevant difference concerning comorbidities according to the Charlson comorbidity index between the cohort groups.…”

Section: Discussioncontrasting

confidence: 82%

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

Hackl

Hierholzer

Friederichs

et al. 2017

BMC Musculoskelet Disord

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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).

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“…The adsorption of BMP‐2 to HAp/Col would be effective not only for sustaining the effect of BMP‐2 but also for preventing complications caused by excessive concentrations of BMP‐2. A clinical study using BMP‐7 combined with a bovine collagen carrier reported that 18% of the cases showed heterotopic ossification that was probably induced by unregulated release of BMP‐7 . Heterotopic ossification can cause serious complications, especially when occurring adjacent to nerve tissue .…”

Section: Discussionmentioning

confidence: 99%

Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein‐2 evaluated using a rat femur osteotomy model

Wei

Egawa

Matsumoto

et al. 2017

Journal Orthopaedic Research

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In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP-2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP-2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP-2 implant. Micro-CT analysis, three-point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP-2 group, and all cases in the HAp/Col + BMP-2 group at 8 weeks post-surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP-2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP-2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129-137, 2018.

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Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

Cited by 16 publications

References 27 publications

Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration

Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration

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

Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein‐2 evaluated using a rat femur osteotomy model

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