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.

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.

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.

The Effect of Platelet Rich Plasma from Bone Marrow Aspirate with Added Bone Morphogenetic Protein-2 on the Achilles Tendon-Bone Junction in Rabbits

BACKGROUND: To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period. METHODS: A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks. RESULTS: Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p < 0.05) at 8 weeks after surgery. CONCLUSIONS: Bone marrow derived PRP and BMP-2 in fibrin glue accelerated healing in a rabbit model of tendon-bone junction injury.