Bone Morphogenetic Proteins: Structure, biological function and therapeutic applications

Bone Morphogenetic Proteins (BMPs) are multifunctional secreted cytokines, which belong to the TGF-beta superfamily. These glycoproteins act as a disulfide-linked homo- or heterodimers, being potent regulators of bone and cartilage formation and repair, cell proliferation during embryonic development and bone homeostasis in the adult. BMPs are promising molecules for tissue engineering and bone therapy. The present review discusses this family of proteins, their structure and biological function, their therapeutic applications and drawbacks, their effects on mesenchymal stem cells differentiation, and the cell signaling pathways involved in this process. (C) 2014 Published by Elsevier Inc.

Calvarial Autogenous Bone Graft for Maxillary Ridge and Sinus Reconstruction for Rehabilitation With Dental Implants

Autogenous bone grafting is the gold-standard technique for bone augmentation procedures prior to implant placement. If the amount of available intraoral donor bone is insufficient, it is necessary to harvest bone graft from extraoral sites, such as calvaria. Although this technique is well established, only a few case reports show the histological analysis of the grafted bone at the moment of implant placement. This article reports the case of a 48-year-old female patient with a critical atrophic maxillary ridge reconstructed using autogenous calvarial bone graft prior to implant placement, with clinical and histological evaluation. Bone was collected under general anesthesia from the parietal bone. The outer cortical originated the bone blocks, and the medullar bone layer between was collected to be used in the sinus augmentation procedure, together with 5 of the bone blocks triturated. Six months after bone augmentation, 8 implants were placed in the grafted area and 2 biopsies were retrieved (anterior and the posterior regions), allowing the visualization of the bone-remodeling process in the grafted areas. The patient had a stable recovery. Our results showed that although necrotic bone could still be seen in the outer layer of the grafted area, the interface between this necrotic bone and the already remodeled bone was consistent with biocompatibility. Two-year radiographic evaluation showed success of the grafts and the implants in supporting an esthetic and functionally stable prosthesis. Summarizing, calvarial bone grafts are a viable alternative for the attainment of adequate bone volume prior to implant placement.

Bone-implant contact around crestal and subcrestal dental implants submitted to immediate and conventional loading

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Remodeling of cortical and corticocancellous fresh-frozen allogeneic block bone grafts - a radiographic and histomorphometric comparison to autologous bone grafts

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bone apposition and surface treatment in dental implants: histomorphometric pilot evaluation in rabbits

The surface of dental implants is an important factor for osseointegration process and different methods of surface treatment have been described. Objective: To investigate the bone apposition in implant surface treated with sandblasting and acid-etching. Material and methods: Ten rabbits were selected and received one implant treated with method I in the left tibia and one implant treated with method II in the right tibia. Then, twenty implants were divided in two groups, according to methods of sandblasting and acid-etching (method I and method II). After 7, 14, 30, 45 and 60 days, tibias were retrieved and submitted to histotechnical procedures. The percentages of bone–implant contact (BIC) and bone area between threads (BABT) were determined throughout histomorphometric analysis and bone apposition was detected in implants of both groups. Results: In BABT measurements, an increase was observed after 45 and 60 days in the method II, compared to method I and no differences were found after 7, 14 and 30 days. In BIC measurements, an increase was detected with method II at 45 days when compared to method I. No differences between groups in BIC values were observed after 7, 14, 30 and 60 days. Conclusion: Our data demonstrated that implants treated with the method II presented increase in the contact between bone and implant after 45 days compared to method I. Moreover, with concern to bone area between threads, it was observed an increased in the method II after 45 and 60 days. However, both groups can be successfully used as a therapeutic strategy to rehabilitation of edentulous patients. Then, further experiments are needed to evaluate, in depth, the putative differential role of each surface treatment.

Peripheral osteoma in the ramus of mandible: report of case

The osteomas are benign rare neoplasms, generally asymptomatic which are characterized by the proliferation of a compact or spongy bone. When they are situated in the maxillofacial area, they affect mainly the mandible, the frontal bone and the paranasal sinus. We have described the case of a female caucasian patient who presented an increased volume in the posterior region of the oral vestibule on the left side. During the clinical examination an oral lesion was observed in the region of the left ramus of mandible. This lesion was motionless, consistent, and painless when palpated. In the image obtained from the computed tomography cone–beam (CBCT), we could observe an hyperdense, cylindrical region, with well defined borders, located in the medial surface of the left ramus of mandible, right below the mandibular notch. Based on clinical data and in the obtained images, we could confirm the presence of the peripheral osteoma in the left side of the ramus of mandible region.

Ovariectomy-associated changes in interradicular septum and in tibia metaphysis in different observation periods in rats

In order to standardize an experimental model to study the effects of absence of ovarian hormones in maxillary bones compared with long bones, the aim of this research was to analyze the influence of ovariectomy (OVX) on rat alveolar bone and tibiae, in different observation periods. Thirty-six female rats were ovariectomized or sham operated. After 60, 90 or 120 days, the animals were sacrificed and their hemimandibles, maxillae and tibiae were removed and routinely prepared for hematoxylin and eosin staining. The percentage of bone matrix area in bone septum in the first molar furcation region, and in tibial metaphysis was calculated, and data were submitted to statistical analysis (p < 0.05). As regards the histomorphometrical analysis in jaw bones, there was no statistical difference between groups, while the effects of ovariectomy on tibiae were seen as early as 60 days. According to the methods used, there was no significant influence of absence of ovarian hormones on interradicular septum of mandibular or maxillary first molars in the periods studied, despite the reduction in bone matrix area in tibia metaphysis as early as 60 days. (C) 2014 Elsevier GmbH. All rights reserved.

Stress distribution around osseointegrated implants with different internal-cone connections: photoelastic and finite element analysis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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 3 mm 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 5 mu g rhBMP-2), P-1 (defect filled with 5 mu g P-1), FS (defect filled with 8 mu g FS), FS/rhBMP-2 (defect filled with 8 mu g FS and 5 mu g rhBMP-2), FS/P-1 (defect filled with 8 mu g FS and 5 mu g 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.

Clinical and surgical management of an aggressive cherubism treated with autogenous bone graft and calcitonin

Cherubism is a rare autosomal-dominant inherited syndrome and is usually self-limiting; it starts in early childhood and involutes by puberty. It is a benign fibroosseous disease, characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses. The purpose of this clinical report is to describe a rare and aggressive form of cherubism on an adult female patient that has been treated in our Bioscience Center for Special Health Care Needs-CEBAPE. The patient was firstly submitted to the surgical procedure with partial curettage of the lesion, and the cavity was filled with autogenous cancellous bone and bone marrow grafts. Furthermore, the support treatment used was the administration of salmon calcitonin by nasal spray during the first year after the preconized procedure. At 4-year followup, we confirmed the stomatognathic system improvement and esthetic rehabilitation, which led to a significant increase in the patient's quality of life.

Exenatide and sitagliptin decrease interleukin 1β, matrix metalloproteinase 9, and nitric oxide synthase 2 gene expression but does not reduce alveolar bone loss in rats with periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health

Purpose: In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Methods: Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (acurrency sign20 ng/mL) were compared to those with levels > 20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). Results: 25OHD levels were similar in patients and controls (21.44 +/- 7.91 vs 22.54 +/- 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (acurrency sign20 ng/mL) were further compared to the 26 JoSLE patients with levels > 20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age (p = 0.100), ethnicity (p = 1.000), BMI (p = 0.911), season (p = 0.502), frequency of vitamin D supplementation (p = 0.587), creatinine (p = 0.751), renal involvement (p = 0.597), fat mass (p = 0.764), lean mass (p = 0.549), previous/current use of glucocorticoids(GC) (p = 1.0), immunosuppressors (p = 0.765), and mean current daily dose of GC (p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 +/- 4.35 vs 1.00 +/- 2.48, p = 0.018), lower C4 levels (12.79 +/- 6.78 vs 18.38 +/- 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 +/- 0.148 vs 0.880 +/- 0.127 g/cm2, p = 0.037) and whole body BMD (0.962 +/- 0.109 vs 1.027 +/- 0.098 g/cm2, p = 0.024). Conclusion: JoSLE vitamin D deficiency, in spite of conventional vitamin D supplementation, affects bone and disease activity status independent of therapy and fat mass reinforcing the recommendation to achieve adequate levels. Lupus (2012) 21, 1335-1342.

Retrospective Clinical Study of 988 Dual Acid-Etched Implants Placed in Grafted and Native Bone for Single-Tooth Replacement

Purpose: To evaluate the influence of sex, implant characteristics, and bone grafting on the survival rate of dual acid-etched (DAE) implants. Materials and Methods: Patients treated with internal-hex DAE implants for single-tooth replacement in a military dental clinic between January 2005 and December 2010 were included in this study. Clinical data related to implant characteristics, implant location, presence of grafted bone, and implant failures were collected. The primary outcome was implant loss. The survival rate was analyzed using the Kaplan-Meier method. Cox regression modeling was used to determine which factors would predict implant failure. Results: DAE implants were evaluated in a total of 988 patients (80.3% men). Twenty-four (2.4%) implants failed, most were cylindric (54.2%) with regular platforms (70.8%) and were 10 mm long (58.3%). The failure rate was 2.4% for the anterior maxilla, 3.3% for the posterior maxilla, 1.6% for the anterior mandible, and 2.0% for posterior mandible. The cumulative survival rate was 97.6%. The failure rate was 8.8% in implants placed after sinus augmentation, 7.3% in bone block-grafted areas, and 1.6% in native bone. Based on multivariable analysis (Cox regression), sinus augmentation and bone block grafting had a statistically significant effect on implant failure; the hazard ratios were 5.5 and 4.6, respectively. Conclusion: The results revealed that DAE implants had high survival rates, and no influence of sex, location, shape, diameter, or length on failure rates could be observed. However, a significant association was observed between failure and presence of bone graft in the implant area. Int J Oral Maxillofac Implants 2012;27:1243-1248

Pore size regulates cell and tissue interactions with PLGA-CaP scaffolds used for bone engineering

A common subject in bone tissue engineering is the need for porous scaffolds to support cell and tissue interactions aiming at repairing bone tissue. As poly(lactide-co-glycolide)calcium phosphate (PLGACaP) scaffolds can be manufactured with different pore sizes, the aim of this study was to evaluate the effect of pore diameter on osteoblastic cell responses and bone tissue formation. Scaffolds were prepared with 85% porosity, with pore diameters in the ranges 470590, 590850 and 8501200 mu m. Rat bone marrow stem cells differentiated into osteoblasts were cultured on the scaffolds for up to 10 days to evaluate cell growth, alkaline phosphatase (ALP) activity and the gene expression of the osteoblast markers RUNX2, OSX, COL, MSX2, ALP, OC and BSP by real-time PCR. Scaffolds were implanted in critical size rat calvarial defects for 2, 4, and 8 weeks for histomorphometric analysis. Cell growth and ALP activity were not affected by the pore size; however, there was an increase in the gene expression of osteoblastic markers with the increase in the pore sizes. At 2 weeks all scaffolds displayed a similar amount of bone and blood vessels formation. At 4 and 8 weeks much more bone formation and an increased number of blood vessels were observed in scaffolds with pores of 470590 mu m. These results show that PLGACaP is a promising biomaterial for bone engineering. However, ideally, combinations of larger (similar to 1000 mu m) and smaller (similar to 500 mu m) pores in a single scaffold would optimize cellular and tissue responses during bone healing. Copyright (C) 2011 John Wiley & Sons, Ltd.

Ultrasuoni focalizzati guidati da imaging di risonanza magnetica: studio delle potenziali applicazioni in campo scheletrico, esempio n.1 - osteoma osteoide

La chirurgia con ultrasuoni focalizzati guidati da MRI (MR-g-FUS) è un trattamento di minima invasività, guidato dal più sofisticato strumento di imaging a disposizione, che utilizza a scopo diagnostico e terapeutico forme di energia non ionizzante. Le sue caratteristiche portano a pensare un suo possibile e promettente utilizzo in numerose aree della patologia umana, in particolare scheletrica. L'osteoma osteoide affligge frequentemente pazienti di giovane età, è una patologia benigna, con origine ed evoluzione non chiare, e trova nella termoablazione con radiofrequenza continua sotto guida CT (CT-g-RFA) il suo trattamento di elezione. Questo lavoro ha valutato l’efficacia, gli effetti e la sicurezza del trattamento dell’osteoma osteoide con MR-g-FUS. Sono stati presi in considerazione pazienti arruolati per MR-g-FUS e, come gruppo di controllo, pazienti sottoposti a CT-g-RFA, che hanno raggiunto un follow-up minimo di 18 mesi (rispettivamente 6 e 24 pazienti). Due pazienti erano stati esclusi dal trattamento MR-g-FUS per claustrofobia (2/8). Tutti i trattamenti sono stati portati a termine con successo tecnico e clinico. Non sono state registrate complicanze o eventi avversi correlati all’anestesia o alle procedure di trattamento, e tutti i pazienti sono stati dimessi regolarmente dopo 12-24 ore. La durata media dei trattamenti di MR-g-FUS è stata di 40±21 min. Da valori di score VAS pre-trattamento oscillanti tra 6 e 10 (su scala 0-10), i trattamenti hanno condotto tutti i pazienti a VAS 0 (senza integrazioni farmacologiche). Nessun paziente ha manifestato segni di persistenza di malattia o di recidiva al follow-up. Nonostante la neurolisi e la risoluzione dei sintomi, la perfusione del nidus è stata ritrovata ancora presente in oltre il 70% dei casi sottoposti a MR-g-FUS (4/6 pazienti). I risultati derivati da un'analisi estesa a pazienti più recentemente arruolati confermano questi dati. Il trattamento con MR-g-FUS sembra essere efficace e sicuro nel risolvere la sintomatologia dell'osteoma osteoide.