transforming-growth-factor-beta and Humeral-Fractures

Surgical 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.. In 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.. One 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.. Aseptic 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.. This 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 ).

Topics: Adult; Aged; Bone Morphogenetic Protein 7; Bone Screws; Bone Transplantation; Diaphyses; Female; Femoral Fractures; Follow-Up Studies; Fracture Fixation, Internal; Fracture Healing; Fractures, Ununited; Humans; Humeral Fractures; Male; Middle Aged; Radiography; Recombinant Proteins; Reoperation; Retrospective Studies; Tibial Fractures; Time Factors; Transforming Growth Factor beta; Young Adult

Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results.

Topics: Adult; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins; Female; Humans; Humeral Fractures; Male; Middle Aged; Ossification, Heterotopic; Postoperative Complications; Radiography; Recombinant Proteins; Transforming Growth Factor beta; Treatment Outcome

To report use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as adjunctive therapy for treatment of a comminuted, open, proximal humeral fracture in an avian species.. Clinical report.. A 3.5-month-old male whooping crane (Grus americana).. An open, severely comminuted humeral facture was stabilized with an intramuscular (IM) pin/type IA external skeletal fixator with tie-in configuration. rhBMP-2 was applied in a calcium phosphate matrix (CPM) paste directly to the fracture site as a bone graft substitute. Radiographic evidence of bone healing was monitored for 14 weeks.. Substantial bony callus was evident at 4 weeks and at 8 weeks there was bridging callus with obvious bony remodeling. The fixation was destabilized at 9 weeks by IM pin removal, bone healing progressed and the fixator was removed at 11 weeks. By 14 weeks both cortices had been re-established with continued callus remodeling evident.. rhBMP-2, applied in a CPM paste, was used as a bone graft substitute in the treatment of a comminuted, open humeral fracture in a whooping crane.. Use of rhBMP-2/CPM should be considered in treatment of avian fractures.

Topics: Animals; Animals, Wild; Birds; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bony Callus; Calcium Phosphates; Fracture Fixation, Internal; Fracture Healing; Fractures, Bone; Fractures, Comminuted; Humeral Fractures; Male; Recombinant Proteins; Transforming Growth Factor beta; Treatment Outcome

To describe outcome in dogs with insufficient bone healing treated with recombinant human bone morphogenetic protein-2 (rhBMP-2).. Retrospective study.. Four dogs clinically affected with delayed union or nonunion bone healing.. Medical records were reviewed for signalment, clinical problem, treatment, and outcome.. Four dogs that had delayed- or nonunion of bone fracture, osteotomy, or arthrodesis were treated with either minimally invasive, fluoroscopically guided, percutaneous administration or direct surgical application of rhBMP-2. Doses used ranged from 0.2 to 1.6 mg of rhBMP-2. In 3 dogs, a calcium phosphate matrix (CPM) carrier was used whereas in 1 dog commercially prepared rhBMP-2 impregnated in an absorbable collagen sponge (INFUSE Bone Graft) was used. This latter dog had osteomyelitis associated with implant infection before rhBMP-2 administration. Rapid radiographic union was noted in all dogs with excellent long-term outcome. Adverse effects were minimal and included transient worsening of lameness after percutaneous administration of rhBMP-2 in 2 dogs.. rhBMP-2 stimulated rapid bone formation at delayed- or nonunion sites resulting in radiographic bone union with minimal adverse effects and excellent long-term outcome in 4 dogs.. Direct intraoperative administration or fluoroscopically guided, minimally invasive delivery of rhBMP-2 may be an effective treatment modality for bone delayed- or nonunions and could potentially be used to stimulate new bone production in a variety of orthopedic surgical conditions in dogs.

Topics: Animals; Biocompatible Materials; Bone Cements; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Collagen; Dogs; Female; Femoral Fractures; Fracture Healing; Fractures, Bone; Humans; Humeral Fractures; Male; Osteotomy; Radiography; Recombinant Proteins; Retrospective Studies; Tendon Injuries; Transforming Growth Factor beta; Treatment Outcome

The purpose of this study was to evaluate the efficacy and safety of recombinant bone morphogenetic protein 7 (rhBMP-7 or OP-1) as a bone-stimulating agent in the treatment of persistent fracture non-unions. Twenty-five consecutive patients [19 males, mean age 39.4 years (range: 18-79)] with 26 fracture non-unions were treated with rhBMP-7. There were 10 tibial non-unions, eight femoral, three humeral, three ulnar, one patellar, and one clavicular non-union. The mean follow-up was 15.3 months. The mean number of operations performed prior to rhBMP-7 application was 3.2, with autologous bone graft and bone marrow injection being used in 10 cases (38.5%). Both clinical and radiological union occurred in 24 (92.3%) cases, within a mean time of 4.2 months and 5.6 months, respectively. Of the remaining two cases, one patient ultimately underwent a below knee amputation, secondary to recurrence of deep sepsis. The other patient with recalcitrant ulnar non-union although the radiological union was incomplete, declined further intervention, as he was asymptomatic. No complications or adverse effects from the use of rhBMP-7 were encountered. This study supports the view that the application of rhBMP-7 as a bone-stimulating agent is safe and a power adjunct to be considered in the surgeon's armamentarium for the treatment of these challenging clinical conditions.

Topics: Adolescent; Adult; Aged; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Transplantation; Female; Femoral Fractures; Femur; Follow-Up Studies; Fracture Fixation, Internal; Fracture Healing; Fractures, Ununited; Humans; Humeral Fractures; Humerus; Knee Injuries; Male; Middle Aged; Patella; Radiography; Recombinant Proteins; Shoulder Fractures; Tibial Fractures; Transforming Growth Factor beta; Ulna Fractures

A prospective study was conducted to determine the efficacy of using recombinant BMP-7 (rhOP-1) as an adjuvant in the treatment of diaphyseal humeral nonunions. Twenty-three consecutive patients with atrophic humeral diaphyseal nonunions were treated at seven separate institutions. All nonunions were fixed with either a compression plate or an intramedullary nail in conjunction with various bone grafting techniques. Recombinant OP-1 was delivered to the fracture site in a Type I collagen carrier at the time of fixation. All fractures went on to eventual union. There were no serious complications and no adverse reactions to the rhOP-I implant. Our study suggests that rhOP-1 may be a safe and effective adjuvant for the treatment of humeral diaphyseal nonunions.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Nails; Bone Plates; Combined Modality Therapy; Female; Fractures, Ununited; Humans; Humeral Fractures; Male; Middle Aged; Neuroprotective Agents; Prospective Studies; Recombinant Proteins; Transforming Growth Factor beta

The potential use of bone morphogenetic proteins (BMPs) to promote bone-healing is of great interest to orthopaedic surgeons. Although the complex mechanism leading from the local presence of BMP (whether endogenous or exogenous) to bone formation is increasingly understood, limited information is available as to whether endogenous BMPs, their receptors, or other molecules involved in their signal transduction, such as Smad1, are present or disappear during the development of fracture nonunions. The purpose of the present study was to determine, by immunohistochemical analysis, whether BMPs, BMP receptors, or Smad1 disappear from tissues during the development of a fracture nonunion.. Twenty-one patients (average age, sixty-one years; range, thirty to eighty-five years) with a delayed union (four patients) or a nonunion (seventeen patients) were included. The average duration of the delayed union or nonunion was twenty-two months (range, 3.5 to 120 months). With use of immunohistochemical analysis, we studied the localization of BMP-2, BMP-4, and BMP-7 and their receptors BMPR-IA, BMPR-IB, and BMPR-II as well as pSmad1. With use of a pSmad1 antibody, we also studied whether the BMP receptors that were expressed were activated.. The immunohistochemical localization of all seven BMP-signaling components was demonstrated in seventeen (81%) of the twenty-one patients. The remaining four patients lacked one or more of the components. Areas of newly formed bone had the highest percentage of positively staining cells, with the staining generally decreasing in areas remote from bone formation. However, even in areas of dense fibrous tissue and in specimens that lacked newly formed bone, immunostaining was still present. The staining patterns showed co-localization of the BMP-2, BMP-4, and BMP-7 proteins with the BMP receptors. The presence of pSmad1 signified the activated state of the BMP receptors, which implies that the BMP signal is transduced inside the cell.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins; Clavicle; DNA-Binding Proteins; Female; Fracture Healing; Fractures, Ununited; Humans; Humeral Fractures; Immunohistochemistry; Male; Middle Aged; Protein Serine-Threonine Kinases; Radius Fractures; Receptors, Cell Surface; Receptors, Growth Factor; Signal Transduction; Smad Proteins; Smad1 Protein; Tibial Fractures; Trans-Activators; Transforming Growth Factor beta