Bone Morphogenetic Protein 2 Plus Leukocyte and Platelet-Rich Fibrin for the Treatment of MRONJ.

Leukocyte and platelet-rich fibrin is known to contain high concentrations of growth factors and when associated with rhBMP-2, it may increase bone remodeling due to its osteoinductive property. The aim of this case is to report the outcome of surgical treatment of medication-related osteonecrosis of the jaw with prototype plate installation and the use of leukocyte and platelet-rich fibrin in association with rhBMP-2 in a 78-year-old female patient under therapy with alendronate. The present Studies describes that the combination of this treatment presented complete healing of osteonecrosis and represents a promising treatment option to be used for medication-related osteonecrosis of the jaw.

The Rise and Fall of Bone Morphogenetic Protein 2 Throughout the United States.

STUDY DESIGN: Retrospective Database Study. OBJECTIVE: Investigate utilization of bone morphogenetic protein (BMP-2) between 2004 and 2014. SUMMARY OF BACKGROUND DATA: The utilization, particularly off-label utilization, of BMP-2 has been controversial and debated in the literature. Given the concerns regarding cancer and potential complications, the risk benefit profile of BMP must be weighed with each surgical case. The debate regarding the costs and potential side effects of BMP-2 compared with autologous iliac crest bone harvest has continued. METHODS: The National Inpatient Sample (NIS) database was queried for the use of BMP-2 (ICD-9-CM 84.52) between 2004 and 2014 across 44 states. The NIS database represents a 20% sample of discharges, weighted to provide national estimates. BMP-2 utilization rates in spine surgery fusion procedures were calculated as a fraction of the total number of thoracic, lumbar, and sacral spinal fusion surgeries performed each year. RESULTS: Between 2004 and 2014, BMP-2 was utilized in 927,275 spinal fusion surgeries. In 2004, BMP-2 was utilized in 28.3% of all cases (N=48,613). The relative use of BMP-2 in spine fusion surgeries peaked in 2008 at 47.0% (N=112,180). Since then, it has continued to steadily decline with an endpoint of 23.6% of cases in 2014 (N=60,863). CONCLUSIONS: Throughout the United States, the utilization of BMP-2 in thoracolumbar fusion surgeries increased from 28.3% to 47.0% between 2004 and 2008. However, from 2008 to 2014, the utilization of BMP-2 in thoracolumbar spine fusion surgeries decreased significantly from 47.0% to 23.4%. While this study provides information on the utilization of BMP-2 for the entire United States over an 11-year period, further research is needed to the determine the factors affecting these trends.

Horizontal ridge augmentation of a single atrophic site in the anterior maxilla using hydroxyapatite and rhBMP-2 / Augmento óseo horizontal de reborde alveolar en sitio atrófico único en maxila anterior usando hidroxiapatita y rhBMP-2

SUMMARY: Bone morphogenetic protein (rhBMP-2) is a powerful osteo-inductive growth factor widely used in bone reconstruction and both the vehicle used to administer it and the scaffold substrate could determine its success in clinical situations. The aim was to analyse the clinical behaviour of dental implants placed in single alveolar ridges with a horizontal deficiency in the maxillary anterior region that were reconstructed horizontally with rhBMP-2 and porous hydroxyapatite (HA). Inclusion criteria were both males and females, between the ages of 18 and 29 with single tooth loss of one upper incisor. Cone Beam Computed Tomography (CBCT) was used to take measurements prior to bone augmentation and again prior to the implant insertion. Surgery was carried out under local anaesthetic. In the primary procedure, bone substitute was introduced using porous HA and rhBMP-2; after 4 to 5 months, dental implant surgery was carried out and the implant placed; after 3 months of consolidation the provisional prosthesis was placed and then a definitive restoration was placed. Variables were analysed using the t-test with a p-value of < 0.05 in order to assess statistical significance. Thirteen subjects were included (6 females and 7 males). Bone augmentation resulted in a bone gain of 4.15mm (p=0.023), which was shown to be statistically significant. All of the grafts placed were successful and 13 implants were placed, using torques between 30 and 70N, without complications. For the final prostheses, 11 were screw retained and 2 were cemented in place. The horizontal bone augmentation using HA and rhBMP-2 is an efficient technique for single bone defects in the anterior maxillary area; clinical trials on a larger scale are needed to confirm these results.

RESUMEN: La proteína ósea morfogenética (BMP-2) es un potente osteoinductor utilizado ampliamente en técnicas reconstructivas; el vehículo de instalación es determinante en su evolución. El objetivo fue analizar el comportamiento clínico de implantes dentales instalados en rebordes alveolares únicos con deficiencia horizontal del sector anterior reconstruida horizontalmente con BMP-2 e hidroxiapatita (HA) porosa. Fueron incluidos sujetos de ambos sexos de entre 18 y 29 años, con pérdida dentaria unitaria a nivel de incisivos superiores. Se utilizó tomografía computadorizada para realizar mediciones en las etapas previa a la instalación del injerto y previo a la instalación del implante. Las cirugías fueron realizadas bajo anestesia local. En la primera intervención se realizó la instalación del injerto óseo utilizando HA porosa y BMP-2; después de 4 a 5 meses se realizó la instalación del implante dental; 3 meses después se realizó la conexión protésica y rehabilitación final. Las variables fueron estudiadas con la prueba t test considerando el valor de p< 0,05 para considerar significancia estadística. Trece sujetos fueron incluidos (6 mujeres y 7 hombres); con la reconstrucción ósea se obtuvo una ganancia ósea de 4,15mm (p=0.023) que fue estadísticamente significativo. No existió pérdida en ningún injerto realizado; se instalaron 13 implantes con torques entre 30 y 70N sin complicaciones; se realizaron prótesis fijas atornilladas en 11 casos y cementadas en 2 casos. La técnica con HA y BMP- 2 es eficiente para reconstruir defectos horizontales en perdidas unitarias del sector anterior maxilar; ensayos clínicos de mayor escala son necesarios para confirmar estos resultados.

Correlation Between Different Interbody Grafts and Pseudarthrosis After Anterior Cervical Discectomy and Fusion Compared with Control Group: Systematic Review.

BACKGROUND: Cervical spine degenerative disease is one of the main causes of myelopathy. Anterior cervical discectomy and fusion (ACDF) is the most common surgical procedure used to treat cervical myelopathy. Therefore, it is important to study pseudarthrosis rates after ACDF and correlate them with the graft used. METHODS: We performed a systematic review to evaluate the relationship between pseudarthrosis after ACDF and the interbody graft used. RESULTS: A total of 3732 patients were evaluated in 46 studies. The mean age of the included patients was 51.5 ± 4.18 years (range, 42-59.6 years). ACDF is most often perforemd as single-level surgery and the level most impaired is C5-C6. The use of titanium cages, zero profile, recombinant human bone morphogenetic protein 2, and carbon cages was seen as a protective factor for pseudarthrosis compared with the autograft group (control group); with an odds ratio of 0.29, 0.51, 0.03, and 0.3, respectively; the results were statistically relevant. The use of polyetheretherketone, poly(methyl methacrylate), and trabecular metal was a risk factor for development of pseudarthrosis compared with the control group, with an odds ratio of 1.7, 8.7, and 6.8, respectively; the results were statistically relevant. Radiologic follow-up was an important factor for the pseudarthrosis rate; paradoxically, a short follow-up (<1 year) had lower rates of pseudarthrosis and follow-up >2 years increased the chance of finding pseudarthrosis. CONCLUSIONS: Different types of grafts lead to a significant difference in pseudarthrosis rates. Follow-up time is also an important factor that affects the rate of pseudarthrosis after ACDF.

Efficacy of rhBMP-2 in Cleft Lip and Palate Defects: Systematic Review and Meta-analysis.

The aim of this study was to analyze the efficacy of using rhBMP-2 (recombinant human morphogenetic protein-2) in the treatment of patients with cleft lip and palate defects (CLPD). Seven databases were screened: PubMed (Medline), Lilacs, Ibecs, Web of Science, BBO, Scopus, and The Cochrane Library. Clinical trials that evaluated the use of bioactive treatment with rhBMP-2 in the treatment of patients with CLPD were included. Statistical analyses were performed by comparing the standardized mean difference of bone formation volume and bone filling percentage (p = 0.05). Ten studies compared the use of rhBMP-2 and iliac crest bone graft (ICBG). The global analysis for bone formation volume and bone filling percentage showed that bioactive materials were similar to ICBG with a standardized mean difference of respectively 0.07 (95% CI - 0.41 to 0.56) and 0.24 (95% CI - 0.32 to 0.80). The available literature suggested that use of rhBMP-2 presented similar bone formation results to those of ICBG in secondary alveolar bone grafting for patients with CLPD.

Combination therapy of canine osteosarcoma with canine bone marrow stem cells, bone morphogenetic protein and carboplatin in an in vivo model.

Osteosarcoma (OSA) is the most common malignant bone cancer in children and dogs. The therapeutic protocols adopted for dogs and humans are very similar, involving surgical options such as amputation. Besides surgical options, radiotherapy and chemotherapy also are adopted. However, hematologic, gastrointestinal and renal toxicity may occur because of chemotherapy treatments. Recent study clearly showed that mesenchymal stem cells (MSCs) combined with recombinant human bone morphogenetic protein (rhBMP-2) may be associated with decreases of the tumorigenic potential of canine OSA. The aim of this study was to analyse the efficacy of chemotherapy with carboplatin and rhBMP-2 with MSCs in a canine OSA in vivo model. Canine OSA cells were implanted in mice Balb-c/nude with MSCs, rhBMP-2 and carboplatin. Flow cytometry and PCR for markers involved in tumour suppression pathways were analysed. Results showed that the combination of MSCs and rhBMP-2 reduced tumour mass and infiltration of neoplastic cells in tissues more efficiently than carboplatin alone. Thus it was demonstrated that the use of rhBMP-2 and MSCs, in combination with conventional antineoplastic, may be an efficient treatment strategy.

Off-label use of rhBMP-2 as bone regeneration strategies in mandibular ameloblastoma unicystic.

Jawbone reconstruction after tumor resection is one of the most challenging clinical tasks for maxillofacial surgeons. Osteogenic, osteoinductive, osteoconductive and non-antigenic properties of autogenous bone place this bone as the gold standard for solving problems of bone availability. However, the need for a second surgical site to harvest the bone graft increases significantly both the cost and the morbidity associated with the reconstructive procedures. Bone grafting gained an important tool with the discovery of bone morphogenetic proteins in 1960. Benefit of obtaining functional and real bone matrix without need of second surgical site seems to be the great advantage of use bone morphogenetic proteins. This study analyzed the use of rhBMP-2 in unicystic ameloblastoma of the mandible, detailing its structure, mechanisms of cell signaling and biological efficacy, in addition to present possible advantages and disadvantages of clinical use of rhBMP-2 as bone regeneration strategy. RESUMO A reconstrução óssea dos maxilares após ressecções tumorais é uma das tarefas mais difíceis para o cirurgião maxilofacial. As propriedades osteogênicas, osteoindutoras, osteocondutoras e não antigênicas do osso autógeno o colocam como o padrão-ouro para a solução de problemas de disponibilidade óssea. Entretanto a coleta do enxerto ósseo necessita de um segundo sítio cirúrgico, aumentando significativamente o custo e a morbidade associados ao procedimento reconstrutivo. A enxertia óssea ganhou uma excelente ferramenta com a descoberta das proteínas ósseas morfogenéticas na década de 1960. O benefício da obtenção de matriz óssea verdadeira e funcional, sem a necessidade de um segundo sítio cirúrgico, parece ser a grande vantagem do uso das proteínas ósseas morfogenéticas. Neste contexto, o objetivo deste estudo foi analisar a utilização da rhBMP-2 na regeneração óssea de ameloblastoma mandibular unicístico, detalhando sua estrutura, seus mecanismos de sinalização celular e sua eficácia biológica, além de apresentar potenciais vantagens e desvantagens da utilização clínica das rhBMP-2, enquanto estratégia regenerativa.

Proteína morfogenética ósea y su opción como tratamiento de la fisura alveolar / Bone morphogenetic protein and its option as an alveolar cleft treatment

La proteína morfogenética ósea (BMP), es una proteína endógena que ha mostrado efectos significativos en la promoción de la formación ósea. El uso de BMP ha sido descrito en la reconstrucción de defectos óseos de origen traumáticos y patológicos, incluyendo la fisura alveolar, el aumento de reborde alveolar, la elevación de seno maxilar, el injerto de alveolo post-extracción, y la cirugía perimplantaria entre otros. A pesar de las ventajas asociadas al uso de BMP y que en la actualidad se aplica en combinación con matrices de colágeno, ciertas propiedades tales como su baja resistencia mecánica y su elevada tasa de liberación inicial disminuyen su eficacia en la formación ósea. En este contexto, el desarrollo de nuevos sistemas de liberación prolongada de BMP que permitan la quimiotaxis de células mesenquimáticas y su posterior diferenciación a osteoblastos representa un desafío con alto potencial clínico para la estimulación de la formación ósea. En este trabajo, se describe el uso de BMP en la reconstrucción de fisuras alveolares y en particular se discuten las ventajas de su administración en micropartículas poliméricas comosistemas de liberación de BMP (rhBMP-2) con promisorias aplicaciones en la estimulación de la formación ósea.

Bone morphogenetic protein (BMP) is an endogenous protein that has shown significant effects in the promotion of bone formation. BMP also has been described in the reconstruction of traumatic and pathological bone defects, including alveolar cleft, alveolar ridge augmentation, maxillary sinus elevation, and applications in post-extraction alveolus graft, and peri-implant surgery among others. Despite the advantages associated with the use of BMP, currently is applied in combination with collagen matrices, which has certain properties such as low mechanical resistance and a high burst initial release that diminish its effectiveness in bone formation. In this context, the development of novel systems with greater mechanical resistance and prolonged release of BMP, that lead to chemotaxis of mesenchymal cells, following by its differentiation to osteoblasts represents a major challenge that holds outstanding clinical potential for the stimulation of bone formation. In this paper, we describe the use of BMP for the reconstruction of alveolar clefts, and its advantages being administrated in polymeric microparticles as sustain release system with promising applications in the stimulation of bone formation.

Off-label use of rhBMP-2 as bone regeneration strategies in mandibular ameloblastoma unicystic / Utilização off-label das rhBMP-2 como estratégia de regeneração do tecido ósseo em ameloblastoma mandibular

ABSTRACT Jawbone reconstruction after tumor resection is one of the most challenging clinical tasks for maxillofacial surgeons. Osteogenic, osteoinductive, osteoconductive and non-antigenic properties of autogenous bone place this bone as the gold standard for solving problems of bone availability. However, the need for a second surgical site to harvest the bone graft increases significantly both the cost and the morbidity associated with the reconstructive procedures. Bone grafting gained an important tool with the discovery of bone morphogenetic proteins in 1960. Benefit of obtaining functional and real bone matrix without need of second surgical site seems to be the great advantage of use bone morphogenetic proteins. This study analyzed the use of rhBMP-2 in unicystic ameloblastoma of the mandible, detailing its structure, mechanisms of cell signaling and biological efficacy, in addition to present possible advantages and disadvantages of clinical use of rhBMP-2 as bone regeneration strategy.

RESUMO A reconstrução óssea dos maxilares após ressecções tumorais é uma das tarefas mais difíceis para o cirurgião maxilofacial. As propriedades osteogênicas, osteoindutoras, osteocondutoras e não antigênicas do osso autógeno o colocam como o padrão-ouro para a solução de problemas de disponibilidade óssea. Entretanto a coleta do enxerto ósseo necessita de um segundo sítio cirúrgico, aumentando significativamente o custo e a morbidade associados ao procedimento reconstrutivo. A enxertia óssea ganhou uma excelente ferramenta com a descoberta das proteínas ósseas morfogenéticas na década de 1960. O benefício da obtenção de matriz óssea verdadeira e funcional, sem a necessidade de um segundo sítio cirúrgico, parece ser a grande vantagem do uso das proteínas ósseas morfogenéticas. Neste contexto, o objetivo deste estudo foi analisar a utilização da rhBMP-2 na regeneração óssea de ameloblastoma mandibular unicístico, detalhando sua estrutura, seus mecanismos de sinalização celular e sua eficácia biológica, além de apresentar potenciais vantagens e desvantagens da utilização clínica das rhBMP-2, enquanto estratégia regenerativa.

Scientific evidence on the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in oral and maxillofacial surgery.

PURPOSE: This study aimed to identify the main indications for the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for bone repair and maintenance in the maxilla and mandible through a review of clinical trials evaluating the viability of using rhBMP-2 to delay the installation of dental implants, thus allowing satisfactory bone formation and long-term osseointegration. METHODS: Literature search of the PubMed/Medline databases was performed using the following MeSH index terms-"bone morphogenetic protein 2" and "dentistry". Only clinical trials necessarily published in English, related to dentistry, and focused on bone reconstruction in critical defects, post-extraction alveoli, increasing the atrophic alveolar ridge, or surgery for maxillary sinus elevation were included, regardless of the age, sex, ethnicity, associated morbidities, or period of publication. RESULTS: Of the 17 studies identified based on the search filters, 2 were excluded. Therefore, 15 studies were finally included in this review. CONCLUSIONS: Based on the results of our review, we concluded that the use of rhBMP-2 for the preservation of the alveolar ridge after tooth extraction or for increasing the local defects is safe and viable. The use of rhBMP-2/Bio-Oss® for the elevation of the maxillary sinus membrane is unnecessary; however, it can improve and accelerate the maturation process in cases of guided bone regeneration in peri-implant defects. Compounds comprising rhBMP-2, allogenic bone, and plasma-rich platelet (PRP) can act as autograft substitutes in mandibular critical defects.

Bone augmentation of the atrophic anterior maxilla for dental implants using rhBMP-2 and titanium mesh: histological and tomographic analysis.

The loss of multiple teeth or trauma to the anterior maxilla often results in a deficient ridge width for prosthetic tooth rehabilitation. This study evaluated the use of titanium mesh and recombinant human bone morphogenetic protein 2 (rhBMP-2) for the repair of major bone defects in the alveolar bone. Five patients were enrolled in the study; these patients required implant replacements for two contiguous missing teeth in the anterior maxilla, which lacked sufficient bone. Residual ridges were augmented with rhBMP-2 and titanium mesh to direct the geometry of the newly formed bone. Seven months later, a bone biopsy specimen was removed from the implantation site before osteotomy and insertion of dental implants. Cone beam computed tomography (CBCT) scans were obtained preoperatively, postoperatively (baseline), and 48 months after implantation to evaluate implant healing. All dental implants were placed in the grafted sites without the need for further bone augmentation. The most frequent adverse effects were facial oedema and oral erythema. Biopsy specimens were used to evaluate bone quality. CBCT scans provided a prediction of alveolar restoration and long-term success. The combination of rhBMP-2 and titanium mesh provided effective augmentation of the atrophic anterior maxilla prior to implant placement.

A new heterologous fibrin sealant as scaffold to recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins for the repair of tibial bone defects.

Tissue engineering has special interest in bone tissue aiming at future medical applications Studies have focused on recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins due to the osteogenic properties of rhBMP-2 and the angiogenic characteristic of fraction 1 protein (P-1) extracted from the rubber tree Hevea brasiliensis. Furthermore, heterologous fibrin sealant (FS) has been shown as a promising alternative in regenerative therapies. The aim of this study was to evaluate these substances for the repair of bone defects in rats. A bone defect measuring 3mm in diameter was created in the proximal metaphysis of the left tibia of 60 rats and was implanted with rhBMP-2 or P-1 in combination with a new heterologous FS derived from snake venom. The animals were divided into six groups: control (unfilled bone defect), rhBMP-2 (defect filled with 5µg rhBMP-2), P-1 (defect filled with 5µg P-1), FS (defect filled with 8µg FS), FS/rhBMP-2 (defect filled with 8µg FS and 5µg rhBMP-2), FS/P-1 (defect filled with 8µg FS and 5µg P-1). The animals were sacrificed 2 and 6 weeks after surgery. The newly formed bone projected from the margins of the original bone and exhibited trabecular morphology and a disorganized arrangement of osteocyte lacunae. Immunohistochemical analysis showed intense expression of osteocalcin in all groups. Histometric analysis revealed a significant difference in all groups after 2 weeks (p<0.05), except for the rhBMP-2 and FS/rhBMP-2 groups (p>0.05). A statistically significant difference (p<0.05) was observed in all groups after 6 weeks in relation to the volume of newly formed bone in the surgical area. In conclusion, the new heterologous fibrin sealant was found to be biocompatible and the combination with rhBMP-2 showed the highest osteogenic and osteoconductive capacity for bone healing. These findings suggest a promising application of this combination in the regeneration surgery.

Use of rhBMP-2/ß-TCP for Interpositional Vertical Grafting Augmentation: 5.5-Year Follow-up Clinically and Histologically.

PURPOSE: This case report documented long-term results using rh-BMP-2/ß-tricalcium phosphate (TCP) for vertical grafting augmentation. MATERIALS AND METHODS: A 58-year-old patient with extreme atrophy of the left posterior mandible was treated with rh-BMP-2/ß-TCP for vertical bone augmentation. At the time of implant placement, bone biopsy was performed for histological evaluation. RESULTS: Seven months after surgery, CT scan demonstrated approximately 8 mm of bone gain height. The histological results revealed a newly formed vital bone tissue, predominantly lamellar with variable density. Remaining bone ceramic surrounded by newly formed bone tissue or connective tissue was observed. The bone levels remained unchanged during the entire period treatment (5.5 years). CONCLUSION: This technique has demonstrated a potential for reconstruction of atrophic sites when vertical bone gain is desirable. Moreover, the bone gain has shown long-term maintenance without resorption. Future long-term prospective clinical trials are needed to confirm these findings.

Cranial vault reconstruction with bone morphogenetic protein, calcium phosphate, acellular dermal matrix, and calcium alginate in mice.

PURPOSE: To evaluate experimental cranial vault reconstructions, by combining bone morphogenetic protein type 2 (BMP-2) and different matrices. METHODS: Fourty-nine animals were initially included (seven per group). We designed an experimental, open, prospective and comparative study, divided in seven groups: 1 - BMP-2+calcium phosphate (BT); 2 - BMP-2+acellular dermal matrix (BM); 3 - BMP-2+calcium alginate (BA); 4 - TCP; 5 - MDM; 6 - ALG; 7 - Bone autograft (BAG). A bone failure was created in left parietal bone of adult male mice. At the same procedure reconstruction was performed. After five weeks, animals were sacrificed, and reconstruction area was removed to histological analysis. After exclusion due to death or infection, thirty-eight animals were evaluated (BT=5; BM=6; BA=6; TCP=7; MDM=3; ALG=6; BAG=5). RESULTS: A higher incidence of infection has occurred in MDM group (57%, P=0.037). In cortical fusion, groups BAG, TCP, and BMP-2+TCP (BT) obtained the best scores, comparing to the others (P=0.00846). In new bone formation, groups BT, BAG, and TCP have presented the best scores (P=0.00835). When neovascularization was considered, best groups were BMP-2+MDM (BM), BMP-2+ALG (BA), TCP, and MDM (P=0.001695). BAG group was the best in bone marrow formation, followed by groups BT and TCP (P=0.008317). CONCLUSIONS: Bone morphogenetic protein type 2 increased bone regeneration in experimental skull reconstruction, especially when combined to calcium phosphate. Such association was even comparable to bone autograft, the gold-standard treatment, in some histological criteria.

Effect of maxillary alveolar reconstruction on nasal symmetry of cleft lip and palate patients: a study comparing iliac crest bone graft and recombinant human bone morphogenetic protein-2.

BACKGROUND: Recombinant human bone morphogenetic protein (rhBMP)-2 has been used in some craniofacial centers worldwide. However, its influence on nasal morphology is unknown. Thus, the objective of this investigation was to assess the effect of maxillary alveolar reconstruction on nasal position and symmetry in unilateral complete cleft lip patients who underwent traditional iliac crest bone grafting transferring versus reconstruction using rhBMP-2. METHODS: Nineteen unilateral complete cleft lip patients were randomly divided into two groups. In group 1, patients underwent traditional iliac crest bone grafting transferring (n = 11) and in group 2, patients underwent alveolar reconstruction using collagen matrix with lyophilized rhBMP-2 (n = 8). Computerized tomography (CT) imaging was performed preoperatively and at 6 months postoperatively using a previously standardized protocol. Linear distances using anatomic landmarks were performed using tridimensional CT data reformatted by the OsiriX(®) software. Quantitative and qualitative measurements to assess intra- and inter-group nasal position modifications were performed. RESULTS: Intra-group pre- and postoperative comparisons showed significant differences (p < 0.05) in two linear measurements of group 1, while group 2 did not present a difference (p > 0.05). Group 2 presented significant postoperative enhancement (p < 0.05) in the quantitative nasal symmetry in one measurement. Qualitative analysis showed postoperative nasal symmetry enhancement in 75% of the measurements of group 2 and 36% of group 1. There was no statistically significant difference in the inter-group comparisons. CONCLUSIONS: Our study demonstrated that both groups showed similar effect on nasal symmetry.

Bone morphogenetic proteins: facts, challenges, and future perspectives.

Bone morphogenetic proteins (BMPs) are members of the TGF-ß superfamily, acting as potent regulators during embryogenesis and bone and cartilage formation and repair. Cell and molecular biology approaches have unveiled the great complexity of BMP action, later confirmed by transgenic animal studies. Genetic engineering allows for the production of large amounts of BMPs for clinical use, but they have systematically been associated with a delivery system, such as type I collagen and calcium phosphate ceramics, to ensure controlled release and to maximize their biological activity at the surgical site, avoiding systemic diffusion. Clinical orthopedic studies have shown the benefits of FDA-approved recombinant human BMPs (rhBMPs) 2 and 7, but side effects, such as swelling, seroma, and increased cancer risk, have been reported, probably due to high BMP dosage. Several studies have supported the use of BMPs in periodontal regeneration, sinus lift bone-grafting, and non-unions in oral surgery. However, the clinical use of BMPs is growing mainly in off-label applications, with robust evidence to ascertain rhBMPs' safety and efficacy through well-designed, randomized, and double-blind clinical trials. Here we review and discuss the critical data on BMP structure, mechanisms of action, and possible clinical applications.

Horizontal ridge augmentation of the atrophic anterior maxilla using rhBMP-2/ACS or autogenous bone grafts: a proof-of-concept randomized clinical trial.

AIM: To compare the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) with autogenous bone graft for augmentation of the edentulous atrophic anterior maxilla. METHODS: Twenty-four subjects were enrolled in a randomized, controlled, parallel-group, open-label clinical trial. Subjects either received rhBMP-2/ACS (1.5 mg/ml) or particulated autogenous bone harvested from the mandibular retromolar region. A titanium-mesh was used to provide space and wound stability. A guide was used to standardize clinical recordings using an analogue caliper. Alveolar ridge width was also assessed using cone-beam computed tomography. RESULTS: rhBMP-2/ACS yielded significantly greater radiographic horizontal bone gain compared with autogenous bone graft at immediate subcrestal levels (1.5 ± 0.7 versus 0.5 ± 0.9 mm; p = 0.01); non-significant differences were observed at mid- (2.9 ± 0.8 versus 2.9 ± 0.9 mm; p = 0.98) and apical (1.7 ± 0.9 versus 1.8 ± 1.1 mm; p = 0.85) crestal levels. No significant differences in clinical horizontal bone gain were observed at 6 months between rhBMP-2/ACS and autogenous bone graft (3.2 ± 0.9 mm versus 3.7 ± 1.4 mm; p = 0.31). Sixty-two implants were placed after 6 month of healing with no significant differences between groups for number of implants, implant size, primary stability and survival. CONCLUSIONS: rhBMP-2/ACS appears a realistic alternative for augmentation of the edentulous atrophic anterior maxilla.

Recombinant human bone morphogenetic protein-2-augmented transforaminal lumbar interbody fusion for the treatment of chronic low back pain secondary to the homogeneous diagnosis of discogenic pain syndrome: two-year outcomes.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To assess clinical outcomes, perioperative complications, revision surgery rates, and recombinant human bone morphogenetic protein-2 (BMP-2)-related osteolysis, heterotopic bone, and unexplained postoperative radiculitis (BMPP) in a group of patients treated with BMP-2-augmented transforaminal lumbar interbody fusion (bTLIF) for the homogeneous diagnosis of discogenic pain syndrome (DPS) and to put forth the algorithm used to make the diagnosis. SUMMARY OF BACKGROUND DATA: There is a paucity of literature describing outcomes of TLIF for the homogeneous diagnosis of DPS, an old but controversial member of the lumbar degenerative disease family. METHODS: The registry from a single surgeon was queried for patients who had undergone bTLIF for the homogeneous diagnosis of DPS, which was made via specific diagnostic algorithm. Clinical outcomes were determined by analyzing point improvement from typical outcome questionnaires and the data from Patient Satisfaction and Return to Work questionnaires. Independent record review was used to assess all outcomes. RESULTS: Eighty percent of the cohort (36/45) completed preoperative and postoperative outcome questionnaires at an average follow-up of 41.9 ± 11.9 months, which demonstrated significant clinical improvement: Oswestry Disability Index = 16.4 (P < 0.0001), 12-Item Short Form Health Survey physical component summary score = 10.0 (P < 0.0001), and a Numeric Rating Scale for back pain = 2.3 (P < 0.0001). The median patient satisfaction score was 9.0 (10 = complete satisfaction), and 84.4% (27/32) of the cohort were able to return to their preoperative job, with or without modification. There were 3 perioperative complications, 4 revision surgical procedures, and 11 cases of benign BMPP. There were no incidents of the intraoperative dural tears or nerve root injury, and litigation involvement (11/36, P > 0.17), preoperative depression (15/36, P > 0.19) or prior discectomy/decompression (14/36, P < 0.37) was not a predictor of outcomes. CONCLUSION: Although limited by retrospective design and small cohort, the results of this investigation suggest that bTLIF is a reasonable treatment option for patients who experience DPS and affords high patient satisfaction. A larger study is needed to confirm these findings. LEVEL OF EVIDENCE: 4.

A prospective, randomized, controlled trial comparing radiographic and clinical outcomes between stand-alone lateral interbody lumbar fusion with either silicate calcium phosphate or rh-BMP2.

OBJECT: Iliac crest autograft has traditionally been considered the gold standard for lumbar spine fusion, though it is not without drawbacks related to harvesting site pain and other complications. Bone graft alternatives, such as recombinant human bone morphogenetic protein 2 (rh-BMP2), are now widely used but also have unique risk profiles and substantially increase costs. The purpose of the current study was to compare the efficacy of rh-BMP2 and synthetic silicate calcium phosphate (SiCaP) as bone graft substitutes on fusion rates and clinical outcomes in patients undergoing single-level lumbar stand-alone extreme lateral interbody fusion (XLIF). METHODS: A prospective, randomized, controlled, clinical, and radiographic study was performed at a single institution. Thirty patients with L4-L5 degenerative disc disease (DDD) were enrolled. Patients were randomized into one of two groups, 15 underwent lumbar single-level stand-alone XLIF using SiCaP, and 15 using rh-BMP2. Clinical and radiographic results were compared between the study groups. Pain (visual analogue scale) and disability (Oswestry disability index) were assessed preoperatively and at postoperative weeks 1 and 6 and postoperative months 3, 6, 12, 24, and 36. Radiographic evaluations were performed at 6, 12, 24, and 36 months. Neurological examinations and adverse events were recorded at each visit. RESULTS: No intraoperative complications were observed in either treatment group, and clinical outcomes were similarly improved between bone graft substitutes from baseline to 36 months postoperative. Complications were transient hip flexion weakness (13%), insufficient indirect decompression (7%), subsidence (17%), excessive bone formation (4%), and adjacent segment disease (14%). Complication rates between the groups were similar, though with slightly more instances of subsidence in the SiCaP group and higher rates of excessive bone formation and adjacent segment disease in the rh-BMP2 group. Rates of fusion at different time points were different between the groups, with the SiCaP patients progressing more slowly toward solid fusion. However, at 36 months, 100% of patients undergoing XLIF achieved solid fusion. CONCLUSIONS: In stand-alone XLIF, SiCaP and rhBMP-2 bone graft substitutes both resulted in complete long-term fusion. rhBMP-2, however, seemed to result in more rapid early postoperative fusion, though with one instance of excessive bone formation in one patient that required subsequent surgical intervention.

Human bone morphogenetic protein-2 use for maxillary reconstruction in cleft lip and palate patients.

BACKGROUND: The conventional methods of maxillary alveolar reconstruction in patient with cleft are the periosteoplasty and autologous bone grafting. As an important alternative of bone substitution, there is the recombinant human bone morphogenetic protein-2 (rhBMP-2). This study compares the rhBMP-2 with periosteoplasty and autologous bone grafting. METHODS: Patients with cleft and alveolar defect were divided into 3 groups of 6 patients who underwent to autologous iliac crest bone grafting, resorbable collagen sponge with rhBMP2, and periosteoplasty, respectively. The analysis was performed through computed tomographic scan preoperatively and at months 3, 6, and 12 postoperatively. The variables analyzed were the alveolar defect volume, formed bone volume, bone formation rate, maxillary height repair rate, and the formed bone density mean. RESULTS: The formed bone volume was similar comparing the bone graft and BMP groups at 1-year postoperative analysis (P = 0.58). Both of them had the formed bone volume significantly larger than the periosteoplasty group at 3 and 6 months postoperatively. In this last group, the 1-year follow-up was canceled because the bone formation was insufficient. The bone formation rate, the maxillary height repair rate, and the mean of density of the formed bone were similar in the bone graft and BMP groups at 1-year follow-up with P values of 0.93, 0.90, and 0.81, respectively. CONCLUSIONS: The amount of formed bone in the periosteoplasty group was insufficient. There was no difference among the bone graft and rhBMP-2 therapy considering the parameters analyzed.