Effect of recombinant human bone morphogenetic protein 7 on bone density during distraction osteogenesis of the rabbit mandible

OBJECTIVES: To examine whether the quality of bone generation in distraction osteogenesis of the rabbit mandible is enhanced by administering recombinant human bone morphogenetic protein 7 (rhBMP-7) to the lengthened site at the end of the distraction phase. STUDY DESIGN: Prospective randomized study of 24 rabbits undergoing distraction osteogenesis of the mandible, followed by injection of rhBMP-7 or a lactate buffer. SETTINGS: McGill University animal care facility. METHODS: Twenty-four white New Zealand rabbits underwent unilateral mandibular osteotomy and application of an Orthofix uniplanar M-100 fixator (Orthofix Inc., Verona, Italy) to the mandible. Mandibular distraction was carried out for 3 weeks. The animals were divided into three groups: group 1 (eight rabbits), control group: distraction, no injection; group 2 (eight rabbits), study group: distaction + injection of 200 microg of rhBMP7-lactate buffer; group 2 (eight rabbits), comparison group: distraction + injection of lactate buffer. All rabbits were sacrificed 7 weeks after surgery. The mandibles underwent radiology and bone densitometry analysis. MAIN OUTCOME MEASURES: Radiology assessment of bone generation within distracted segments and objective analysis of bone mineral density. RESULTS: Radiology confirmed the presence of bone generate within distraction sites. Densitometry showed a difference in bone mineral density among the three groups (p < .05). CONCLUSION: Local injection of a single dose of 200 microg of rhBMP-7 did enhance bone density when compared with the control group, although not in a statistically significant way when analyzed by an x-ray bone densitometer. This study serves as a starting point for future studies in bone tissue engineering by guiding the strategic administration of rhBMPs and the use of new state-of-the-art technologies, such as micro CT scanning, to analyze in a more detailed way, the effects of rhBMP administration.     

Improvement of maxillofacial bone distraction osteogenesis: future prospects

Distraction osteogenesis is a tissue engineering technique based on Ilizarov's study on long bones. Mc Carthy transposed it rapidly to facial bones. His results in cranial and maxillofacial surgery are good and reproducible. However, the current protocols are long and the devices used are bulky. Finding new devices and association with other tissue engineering techniques should improve distraction osteogenesis and the patient's comfort.     

Distraction osteogenesis of the mandible

PURPOSE OF REVIEW: Airway obstruction and craniofacial deformities resulting from mandibular deficiency are challenging and complex clinical problems. Mandibular distraction osteogenesis is playing a rapidly expanding role in the treatment of these children and has supplanted traditional management techniques in many centers. Several recent studies have reviewed clinical experience, described technical refinements, and addressed issues in patient selection and preoperative workup. RECENT FINDINGS: The extension of mandibular distraction osteogenesis to newborns with Pierre Robin sequence or craniofacial syndromes associated with micrognathia and airway obstruction has radically altered treatment protocols at several institutions. Early bilateral mandibular distraction has obviated tracheostomy in most newborns, with low operative morbidity. In addition, early decannulation and resolution of obstruction has occurred when mandibular distraction osteogenesis was applied to selected micrognathic children. Some of these patients were tracheotomized and others presented with severe obstructive symptoms. Studies have described success with external and internal distraction techniques. Recent publications have also demonstrated the surgeon's ability to mold the regenerate safely, the dynamic characteristics of the consolidation phase, and success with secondary and tertiary distraction. SUMMARY: After 15 years of clinical use in children for craniofacial deformities, recent advances in distraction osteogenesis have obviated tracheostomy in most newborns with micrognathia and severe airway obstruction. Applications of this technique to children with airway issues related to micrognathia or retrognathia have been rapidly expanding. In addition, refinements in distraction technique have advanced treatment of nonairway-related mandibular deformities.     

Distraction osteogenesis of the mandible for airway obstruction in children

OBJECTIVES: Objectives of the study were to determine the effectiveness of distraction osteogenesis of the mandible to relieve airway obstruction in children with tongue-base airway obstruction and to describe the new surgical techniques developed for use in infants and young children. STUDY DESIGN: Prospective, nonrandomized study. METHODS: Analysis of 11 children with severe airway obstruction secondary to tongue-base obstruction was performed. Patients were between 2 weeks and 5.5 years of age. All patients underwent distraction osteogenesis of the mandible. RESULTS: Twelve distraction procedures in the 11 children in the study were accomplished; decannulation or extubation was successful in all children. CONCLUSION: Distraction osteogenesis of the mandible can be used to treat tongue-base airway obstruction in appropriately selected children.     

Aneurysmal bone cyst of the mandible

Aneurysmal bone cyst is an uncommon benign lesion that rarely presents in the craniofacial region. No prior reports of this entity involving the mandible could be found in the otolaryngologic literature, and it has been reported only infrequently in the maxilla. Two previously unreported cases originating in the mandible are presented with a review of the literature, pathology, and diagnosis of this lesion. Treatment of this lesion consists of complete surgical removal and immediate bone grafting for reconstruction.     

Aneurysmal bone cyst of the mandible

The aneurysmal bone cyst (ABC) is a benign, solitary lesion of bone which is most commonly found in the long bones and vertebral column. Its occurrence in the mandible is uncommon. Because of its infrequent appearance, the ABC may be mistaken for neoplastic lesions. In the past, management has consisted of curettage, cryotherapy and local resection. In this publication we present a case of ABC of the mandible. We include a review of the literature, a discussion of the etiology, pathogenesis and management of this interesting lesion.     

Vertical distraction osteogenesis of the alveolar process using a tooth-borne device]

Since the communication of McCarthy et al. in 1992, applications for distraction osteogenesis in the maxillofacial complex have increased enormously. The advantages as compared to conventional reconstructive procedures are missing donor-site morbidity for bone graft harvesting, reduced blood loss and also a gradual gain in the soft tissue envelope. Meanwhile, even the vertical lengthening of the alveolar process has become a clinically reliable method. The case presented illustrates the treatment of a 16-year-old patient who suffered a sporting accident at the age of 7 years, leading to ankylosis of the upper middle incisors with subsequent underdevelopment of the frontal alveolar process. After fabrication of a custom-made distraction device, an osteotomy of the tooth-bearing segment in the upper front was performed and the segment was attached to the distraction device. Bone lengthening was started on the seventh postoperative day at a daily rate of 0.5 mm. The distraction was maintained until closure of the open bite was achieved. On the 22nd day, the segment was fixed using an orthodontic arch wire and the distraction device was removed. A retention period of 6 weeks was maintained until sufficient stability was detectable. Now, 1.5 years after the treatment, the situation is stable with a good consolidation of the bone fragments and a physiologically shaped gingivobuccal sulcus. Lengthening of the alveolar process by vertical distraction osteogenesis using a tooth-borne device may be indicated in certain cases. With this technique a second operation can be avoided and there is less risk of laceration of dental roots by fixation screws.     

The role of bone morphogenetic protein 4 in inner ear development and function

Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF-beta superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null (Bmp4(+/-)) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4(+/-) mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4(+/-) mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4(+/-) mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4(+/-) mice have structural and functional deficits in the inner ear.     

Comparison of the osteogenic activity of bone morphogenetic protein (BMP) mutants]

BACKGROUND: Modification of the heparin binding site by alteration of the amino acid sequence of bone morphogenetic protein-2 (BMP-2) results in a change in the local retention time. The purpose of this study was to compare the osteogenic activity of T3 and T4, two mutants with increased binding capacity to heparin, and B2GDF-5 a mutant resulting from the fusion of the n-terminal amino acid sequence of BMP-2 and the c-terminal sequence of GDF-5 with wild-type BMP-2 in vivo. MATERIAL AND METHODS: The proteins were coupled to an equine-derived collagen carrier and implanted in standardized critical size calvarial defects in adult rats. After 28 days, bone formation was evaluated radiographically and the new bone was characterized histologically. RESULTS: Proteins T3 and T4 showed a higher osteogenic activity than BMP-2. Less new bone formation was observed with GDF-5 and B2GDF-5 than with-type BMP-2. No difference in bone formation was observed between GDF-5 and B2GDF-5. CONCLUSION: Increased heparin binding capacity enhances osteogenic activity of BMP-2 in vivo. This might be due to a longer retention period in the tissue and thus better bioavailability. Replacement of the N-terminal amino acid sequence of GDF-5 by the corresponding sequence of BMP-2 did not result in an increased osteogenic activity as heparin binding capacity is not the main reason for the bioavailability of GDF-5.     

Signaling by way of type IB and II bone morphogenetic protein receptors regulates bone formation in otospongiosis

HYPOTHESIS: The main goal of this study was to perform an immunohistologic analysis of bone morphogenetic protein receptors (BMPR) in otospongiosis. BACKGROUND: BMP-2, -4, and -7 play an essential role in bone formation and repair. They do so as well in otosclerosis. It has been shown that these BMPs are traceable in osteocytes and osteoclasts in the active phase of otosclerosis (otospongiosis). The role of the different BMP receptors in otosclerotic bone transformation has not been previously analyzed. METHODS: The posterior parts of the stapes footplates, collected during partial stapedectomies in 35 patients with clinical otosclerosis, were analyzed for histologic otosclerotic lesions after hematoxylin staining. Immunohistochemical analysis was performed using polyclonal immunoglobulin G antibodies for BMPR-IA, -IB, and -II, as well as biotinylated secondary antibodies, avidin-biotin-peroxidase complex reaction, and alkaline phosphatase staining with nitroblue-tetrazolium-chloride. RESULTS: Seventeen of 35 (49%) specimens contained otosclerosis, but only 5 of these exhibited an otospongiotic phase. The abundant osteoblasts and osteoclasts in these cases showed distinct immunochemical staining for BMP-2, -4, and -7. In two cases, there could also be found an immense positive staining for BMPR-IB and modest staining for BMPR-II, whereas BMPR-1A always remained negative. CONCLUSION: It was demonstrated for the first time that in otospongiosis, the actions of the BMPs are mediated through BMPR-IB and BMPR-II. To determine this role in detail, further investigations, especially for the phosphorylated Smad proteins within the BMP dependent mediator cascade, will be necessary.     

新型HA-BMP复合人工听小骨临床应用观察

目的：对一种新型HA-BMP复合人工听小骨临床应用的效果进行评价。方法：对2000-2005年进行鼓室成形术的59例（61耳）患者进行随访。使用HA-BMP复合人工听小骨行鼓室成形术的26耳,其中全听骨赝复物7耳,部分听骨赝复物19耳;使用自体残余听骨重建者18耳;单纯大鼓室Ⅲ型手术17耳。结果：平均随访时间31.2个月;使用新型HA-BMP复合人工听小骨者的听力提高明显优于使用自体组织重建听骨链和单纯大鼓室Ⅲ型手术患者（均P〈0.01）,结果按照术后平均语频气骨导差小于20 dB为成功标准,HA-BMP复合人工听小骨组成功率为92.3%,随访均未见听骨脱出。结论：新型HA-BMP复合人工听小骨具有良好的生物相容性和优异的传音性能,明显优于自体组织,临床应用效果稳定,具有广泛的应用前景。     

Defect repair in the rat mandible with bone morphogenic protein 5 and prostaglandin E1

OBJECTIVE: To compare the osteogenic abilities of 2 growth factors (bone morphogenic protein 5 [BMP-5] and prostaglandin E1 [PGE1]) and 2 carriers (collagen/polylactic acid [PLA] and collagen/calcium hydroxyapatite cement [HAC]) in the repair of a rat mandibular body defect. DESIGN: Prospective controlled trial.Subjects Twenty-nine Sprague-Dawley rats. INTERVENTIONS: Critical size defects were created in the bilateral mandibular bodies of the rats. Each hemimandible was assigned to an experimental group. The defects were filled with PLA (group 1), PLA with BMP-5 (group 2), PLA with PGE1 (group 3), HAC (group 4), HAC with BMP-5 (group 5), or HAC with PGE1 (group 6). The control group (group 7) had unfilled defects. The animals were killed after 12 weeks, and the nondemineralized specimens were processed histologically. Stereologic techniques were used to determine the volume fractions of new bone, osteoid, marrow, remaining implant, and fibrous tissue in each defect. RESULTS: The HAC/BMP-5 group (group 5) contained significantly more new bone than the PLA/BMP-5 group (group 2) (P =.02), the HAC and HAC/PGE1 groups (groups 4 and 6) (P =.002), and the control group (group 7) (P<.01). The HAC/BMP-5 group also had less fibrous tissue than the HAC group and the HAC/PGE1 group (P<.001). Groups 5 and 6 had less fibrous tissue than group 7 (P<.01). The groups containing PGE1 demonstrated significantly more osteoid development than the other experimental groups (P<.001). CONCLUSIONS: Inclusion of BMP-5 in an implant with calcium hydroxyapatite cement resulted in the formation of significantly larger fractions of new bone and less fibrous tissue ingrowth than occurred in the other experimental groups. The presence of PGE1 resulted in larger amounts of osteoid deposition, suggesting the potential for delayed bone healing.     

Cranial, iliac, and demineralized freeze-dried bone grafts of the mandible in dogs

Both autogenous bone grafts and demineralized freeze-dried allogeneic bone implants were evaluated for mandibular reconstruction. Four-centimeter segmental defects of the midbody of the edentulous mandible were reconstructed in 36 dogs, with specimens recovered at 3 and 6 months and quantitatively compared for total and new bone by histomorphometric analysis. Autogenous grafts consisted of corticocancellous cranial block (CB), corticocancellous iliac block (IB), and particulate cancellous iliac marrow (PM). The allogeneic bone was demineralized and freeze-dried, and consisted of particulate cortical endochondral bone (FP), cranial cortical block (FCB), and iliac cortical block (FIB). Clinically and histomorphometrically, results appeared to indicate that (1) CB compared favorably with IB at 3 and 6 months for total bone, but IB showed a trend for more new bone formation at 6 months, a trend that may be due to the thicker cortical component of CB, which requires longer time periods to remodel than the cancellous rich IB; (2) FP failed to achieve bony union at 3 months, with inadequate rates of new bone formation; and (3) FCB and FIB compared favorably for total bone with CB and IB at 6 months, although new bone for autogenous CB and IB was 26.9% and 45.4%, while new bone for allogeneic FCB and FIB represented only 7.9% and 17.4%.     

Solid aneurysmal bone cyst of the mandible

Aneurysmal bone cyst is a rare, rapidly expanding, locally destructive, and often misdiagnosed lesion. It accounts for about 1-2% of primary biopsied bone tumours. About 60-70 cases have been reported in the jaws; particularly the molar regions. Eighty percent of patients are under 20 years of age. Aneurysmal bone cyst exists as a primary or secondary lesion. It may be conventional (95%) or solid (5%). The solid variant is more difficult to recognize. The practical importance of aneurysmal bone cyst lies in the fact that it must be differentiated from malignant tumours: mainly with giant cell tumours and teleangiectatic osteosarcoma.     

Atypical Stafne bone cavity of the mandible

The paper presents the case of atypical Stafne bone cavity in 41 years old male. The defect was situated under the mandibular nerve and second molar. There were the part of submandibular gland, arterial vesel and fat tissue in the 2 x 2 cm cavity.     

喉软骨支架缺损应用骨形态发生蛋白再生的实验研究

目的 :观察骨形态发生蛋白 纤维蛋白复合物 (BMP FG)、骨基质明胶 (BMG)、羟基磷灰石 (HA)在行犬甲状软骨缺损移植修复中的效果 ,为寻求一种理想的移植材料提供实验依据。方法 :制备甲状软骨缺损动物模型 ,将其分为 4组 :空白组、HA组、BMG组和BMP FG组 ,分别用相应的上述材料进行修复 ,并于术后 1、2、4、8和12周随机抽取一定数量的犬取材行大体标本观察 ,光镜和电镜检测。结果 :BMP FG和BMG均能诱导缺损部位形成软骨或骨 ,但前者效果明显优于后者 ;HA不能将缺损形成良好修复。结论 :BMP FG是喉软骨缺损修复的良好材料 ,优于BMG ,HA修复效果较差     

骨形态发生蛋白-羟基磷灰石复合人工听小骨动物实验研究

目的 :寻找一种生物相容性好并且能被机体骨组织替代的听骨链重建材料。方法 :用骨形态发生蛋白(BMP)复合多孔羟基磷灰石 (HA)听小骨 ,模拟在人行鼓室成形术的条件植入兔的听泡内。分别于术后 1、 2、 4、 8、12、 16周处死动物 ,取材作大体及组织病理学观察 ,了解该种新型听小骨 (BMP/ HA)的成骨效应 ,并与单纯 HA材料听小骨相比较。结果 :将 BMP/ HA听小骨植入兔听泡后 4周 ,人工听小骨表面被覆与正常粘膜结构一致的上皮细胞 ,鼓膜面周围大量间充质细胞生长 ;12周时在鼓膜与听小骨之间有软骨形成 ,16周发现有新骨生成。各时间组植入材料与听泡骨壁之间无过度纤维组织增生。对照组未见新骨生成。结果 :BMP/ HA人工听小骨是一种具有较强骨诱导能力、生物相容性良好的人工听小骨 ,作为中耳传音结构重建材料 ,有可能优于单纯羟基磷灰石人工听小骨。