Evaluation of inferior alveolar nerve function during distraction osteogenesis in the dog

Purpose: A series of electrophysiologic studies were performed in a canine model to evaluate inferior alveolar nerve (IAN) function during distraction osteogenesis of the mandible.Materials and Methods: Fourteen dogs, including two controls, were used in the study. Twelve dogs underwent a 10-mm bilateral mandibular lengthening with an intraoral bone-borne appliance and midbody osteotomy. By using sensory nerve action potentials, IAN function was assessed before and immediately after surgery, before and at the completion of distraction, and before necropsy after 4, 6, or 8 weeks of fixation.Results: Twelve of the 24 nerves showed a complete loss of evoked potential after surgery without recovery at any point throughout the study. Acute nerve injury caused by either the osteotomy or screw encroachment was identified at necropsy. The other 12 nerves showed reproducible responses after surgery. Eight of these nerves had significant amplitude attenuation of the evoked potentials, which was identified at necropsy as a result of acute injury. The remaining four nerves did not show significant evoked potential abnormalities and appeared to be grossly normal at necropsy. During distraction, the amplitude of evoked potentials in all 12 nerves remained at the postoperative level, whereas latency showed a significant delay. In 7 of these 12 nerves, various degrees of evoked potential recovery were identified at the completion of the study.Conclusions: The high incidence of acute IAN injury in the current study was primarily related to device construction and osteotomy technique. If acute nerve injury is avoided at surgery, distraction osteogenesis with 10 mm mandibular lengthening appears to produce minimal deleterious effect on IAN function.     

下颌骨牵引成骨术对下牙槽神经功能影响的实验研究

目的　研究下颌骨牵引成骨术对下牙槽神经功能的影响。方法　对青年恒河猴 16只 ,全麻下行下颌角部骨截开术及牵引器置入术 ,术后第 5天开始以 0 5mm× 2次 /d的速度牵引 ,共15d。采用八导肌电图仪 ,表面电极在颏孔处刺激 ,针电极在卵圆孔附近记录 ,分别在术前、牵引完成后 0、2、4、6、9、12周时行感觉神经动作电位测试。结果　牵引完成时潜伏期较术前增加 2 2 18% ,其后逐渐降低 ,至牵引完成后 12周时仍较术前高 10 70 %。牵引完成时波幅降至术前的 2 8 5 4% ,牵引后 12周时恢复至术前的 99 84%。结论　下颌骨牵引成骨术对下牙槽神经的功能会产生暂时性影响 ,随着神经髓鞘和轴突的再生 ,神经功能可逐渐恢复正常。     

变速牵引成骨对兔下牙槽神经的影响

目的　研究变速牵引兔下颌骨15mm对下牙槽神经的影响。方法　5只新西兰白兔单侧下颌骨截开。延迟5d ,以每天1 5mm ,每天2次牵引9mm ,然后继续以每天1mm ,每天2次牵引6mm ,完成牵引后固定15周,分别行肉眼及组织学观察和电生理学检查。结果　下颌骨延长15mm ,新骨生成良好。下牙槽神经牵长2 1. 99% ,牵引结束时神经变性明显,感觉神经动作电位波幅下降为术前的9. 70 % ,潜伏期较术前有所延长,随后出现恢复趋势,到固定15周时,波幅恢复到术前的33. 85 % ,潜伏期基本恢复正常。结论　下颌骨变速牵引15mm后,下牙槽神经受到明显的影响,到15周时,下牙槽神经的功能有恢复的趋势,但恢复尚不完全。     

Complications in alveolar distraction osteogenesis of the atrophic mandible

To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8mm, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1 to 7 years. Associated complications, as occurred during instalment of the distractor device, VDO period and consolidation phase, and also after dental implant placement, were evaluated. Observed complications were: early fractures (2%), late fractures (17%), bleeding or haematoma (4%), infections (6%), skin perforation (2%), mucosal dehiscence (8%), sensory disturbances (28%), sagging chin (13%) and failure of dental implants (13%). In 10 patients 2 complications and in 1 patient 3 complications were monitored. All complications occurred in the first year. It is concluded that VDO to restore vertical bone height in patients with mandibular atrophy is a surgically delicate technique with a high risk of various complications. The likelihood of the most striking complication, namely fracture occurrence, increases with decreasing residual bone height.     

失感觉神经支配大鼠下颌骨牵张成骨动物模型的建立

目的：建立一个新的可行性和重复性俱佳的失感觉神经支配大鼠下颌骨牵张成骨模型。方法：24只大鼠随机分为2组,实验组大鼠先自下颌孔至颏孔切除下齿槽神经后,从升支前缘至下颌骨下缘行全层骨切开,用螺钉固定特制的钛牵张器,对照组为保留下齿槽神经的大鼠下颌骨牵张成骨,5d延迟期后,均进行单侧下颌骨牵张,速率：0．2mm／12h,牵张期为lOd,随后进入固定期。分别于固定期第14d、28d处死大鼠,进行大体标本观察和组织学检测。结果：实验过程被所有24只大鼠很好的耐受,切口感染率低,无牵张器脱落。大体标本观察表明,在牵张间隙形成了很好的骨痂组织,牵张间隙达到了预期的长度。感觉神经缺失对牵张成骨具有负面调节作用。结论：成功建立了一个新的可行性和重复性俱佳的失感觉神经支配大鼠下颌骨牵张成骨模型,该模型有助于感觉神经对牵张成骨影响的分子机制的进一步深入研究。     

下颌骨牵引延长后下齿槽神经功能的评价

目的 采用三叉神经体感诱发电位（trigeminal somatosensory evoked potential,TSEP)检查恒河猴下颌骨牵引延长术对下齿槽神经功能的影响。方法 健康青年恒河猴7只，行下颌角部完全骨截开术，右侧或双侧安放牵引器。截骨间隙平均牵引距离为13．5mm。于术前、牵引完成时、牵引完成后4周分别进行下齿槽神经SEP检查。结果 术前下齿槽神经SEP各波的潜伏期测量值，两侧对比检验差异无显著性。牵引术完成时SEP各波的潜伏期较术前均有不同程度延长（P＜0．01，P＜0．001），波幅显著下降（P＜0．001）。术后4周各波潜伏期及波幅均有恢复，但多数差别仍有显著性。结论 TSEP检查提示下颌骨牵引延长术对下齿槽神经功能有一定影响，术后4周其功能有部分恢复。     

Expression of nerve growth factor and vascular endothelial growth factor in the inferior alveolar nerve after distraction osteogenesis

The objective of this study was to evaluate changes occurring in the inferior alveolar nerve (IAN) subsequent to mandibular distraction osteogenesis, with regard to the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on 8 mongrel dogs. Two animals were killed at 7, 14, 28 and 56 days after completion of distraction. The distracted IAN and contralateral control nerve were then harvested and analysed histologically and immunohistochemically. Signs of acute nerve injury, including demyelination, were observed in the distracted IAN on the 7th and 14th day after distraction. At 56 days, the histological features of the distracted IAN were similar to those of the control nerve. The levels of NGF and VEGF expression were significantly elevated on the 7th and 14th day after distraction. NGF was expressed in most of the distracted nerve tissues, but VEGF was primarily detected in Schwann cells and the neurovasorum. VEGF expression had returned to normal but NGF expression was still profoundly elevated 28 days after distraction. NGF expression returned to normal levels at 56 days after distraction. NGF and VEGF appeared to have been elicited from the Schwann cells and damaged nervous tissues, and they may play important roles in the initial healing of damaged nerves. VEGF expression returned to normal more quickly than did NGF expression. This may indicate that hypoxic conditions within the distracted nerve had recovered to normal during the early stages of consolidation. Micro-vessels in the distracted nerve may have recovered more rapidly than did the nerve tissue itself.     

Co-expression of nerve growth factor and p75NGFR in the inferior alveolar nerve after mandibular distraction osteogenesis

During mandibular distraction osteogenesis (DO), the inferior alveolar nerve (IAN) is damaged during distractor activation, but spontaneously recovers during consolidation. Although many neurotrophic factors are known to play critical roles, there have been few studies on the mechanism of peripheral nerve recovery after DO. The aim of this study was to observe the expression pattern of p75NGFR (low-affinity receptor of NGF) and to detect autocrine growth activity in IANs following mandibular DO. Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on eight mongrel dogs. Two each were killed at 7, 14, 28 and 56 days after completing distraction. The distracted IAN and contralateral control nerve were harvested. Immunohistochemical staining was performed to determine p75NGFR expression, and double immunofluorescent staining to detect NGF and p75NGFR co-expression. Levels of p75NGFR expression were found to be significantly elevated at 7 and 14 days in Schwann cells located in the outer layer of axon, but were almost undetectable at 28 and 56 days. In double immunofluorescent images, the co-expression of NGF and p75NGFR was also detected at 7 and 14 days. p75NGFR plays an important role in remyelination due to its abundant expression in Schwann cells of damaged nerves, and NGF is an autocrine growth factor present in distracted IANs during the early consolidation period after mandibular DO.     

牵张成骨对下颌骨发育的影响

牵张成骨因能减小手术创伤、减少术后并发症并增加术后稳定性而得到学者们的青睐.随着在一些综合征患者或先天畸形患者治疗中的应用,牵张成骨对下颌骨发育的影响越来越受到学者们的关注.本文就下颌骨牵张成骨对下颌骨发育影响的研究进展作一综述.     

Evaluation of alveolar nerve function after surgical lengthening of the mandible by a bilateral sagittal split osteotomy or distraction osteogenesis

This study compares the effects of bilateral sagittal split osteotomy (BSSO) and distraction osteogenesis (DO) for lengthening the mandible regarding loss of function of the inferior alveolar nerve (IAN). In a retrospective cohort study design, the function of the IAN was tested with a Weinstein monofilament 3.22, 1 year after the surgical procedure in 65 patients (35 BSSO; 30 DO). This was defined as the upper limit for normal function. Of 130 IAN studied (70 BSSO, 54%; 60 DO, 46%), nerve function was disturbed in 23 (18%). In this group, 14 cases (61%) had undergone BSSO and 9 (39%) DO. One-hundred and seven nerves had no neurosensory IAN changes; of these BSSO had been performed in 56 cases (52%) and DO in 51 cases (48%). After eliminating confounding factors, there was no significant difference in the occurrence of neurosensory changes between the treatment options (DO versus BSSO, odds ratio: 1.254 with 95% CI: 0.366–4.300). In conclusion, there was no difference in IAN function between patients treated with BSSO or DO for lengthening the mandible.     

下齿槽神经缺失大鼠下颌骨牵张成骨牵张期蛋白质组学分析

目的：探讨用蛋白质组学iTRAQ技术分析下齿槽神经缺失大鼠下颌骨牵张成骨牵张期新生组织蛋白表达的改变.方法：6只大鼠随机分为2组,实验组为下齿槽神经缺失大鼠下颌骨牵张成骨,对照组为正常大鼠下颌骨牵张成骨,均进行单侧下颌骨牵张,速率：0.2mm/12h,牵张期为10d,下颌骨牵张成骨牵张期第10d取材.将取材的新生骨组织标本进行理化性分析、蛋白质提取及蛋白质定量检测.应用iTRAQ技术对蛋白质样本进行检测,寻找及鉴定差异蛋白.结果：应用iTRAQ技术质谱鉴定出置信度95％的蛋白315种,共鉴定出差异蛋白146个,其中上调≥1.5倍的39个,下降≤0.8倍的58个.结论：感觉神经系统在牵张成骨的成骨过程中起到一定调控作用.筛选出多种下齿槽神经缺失下颌骨牵张成骨牵张期新骨形成相关的差异蛋白,为进一步验证感觉神经缺失对下颌骨牵张成骨新骨形成相关蛋白质奠定了基础.     

The role of nerve growth factor and brain-derived neurotrophic factor in inferior alveolar nerve regeneration in distraction osteogenesis

Distraction osteogenesis (DO) has become the mainstay of treatment of mandibular hypoplasias. Despite the clinical acceptance of the technique in the last decade, little is known of the biological mechanism of bone and soft tissue regeneration. The biological response of peripheral nerves to distraction has not been well documented. This study examined the role of two neurotrophic molecules, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in DO on nerve regeneration of the inferior alveolar nerve (IAN) in an ovine mandible model. Twelve animals were randomly divided into three groups and distracted at 5, 10, and 15 days using a mandibular osteotomy and uniaxial external distractor. The mental nerves and the IAN from the distracted site were harvested at the end of the distraction period and examined for the presence of NGF and BDNF using immunohistochemistry. Nerve growth factor expression was increased at both sites, whereas BDNF was only expressed at the mental nerve on the distracted side. Nerve growth factor and BDNF are involved in the response of the peripheral nerves to injury. Mechanical force applied to the IAN by distraction may lead to detachment of Schwann cells from their axons, leading to segmental degeneration. The resulting myelin sheath debris may serve as a trigger for higher expression of NGF and BDNF, facilitating Schwann cell proliferation and remyelination of the affected segment. Distraction of the mandible may serve as a source of subacute injury to the IAN and influence NGF and BDNF.     

Vertical alveolar distraction osteogenesis with complications in a reconstructed mandible

We report here a case of vertical alveolar distraction osteogenesis with many complications that required further surgical interventions. A 54-year-old man underwent mandibular resection followed by iliac bone grafting as the result of large mandibular odontogenic keratocyst. Eleven months later, alveolar vertical distraction osteogenesis was applied to the patient for prosthetic rehabilitation. Fracture of the basal bone occurred in the consolidation period, and the fracture was fixed by the titanium miniplate system. Radiographic examination after completion of distraction osteogenesis confirmed a radiolucent area in half of the distracted area between the basal bone and the transport segment, and when the distractor was removed the radiolucent area was filled with fibrous granulation tissue. The granulation tissue was removed and endosteal implants were inserted together with a bone graft. Ultimately, all implants were osseointegrated, and adequate esthetics and function of the implant-supported prosthesis were achieved.     

Bilateral sagittal split osteotomies versus mandibular distraction osteogenesis: a prospective clinical trial comparing inferior alveolar nerve function and complications

The aim of this study was to conduct a prospective clinical trial comparing the neurosensory function of the inferior alveolar nerve (IAN) after mandibular advancement surgery with either bilateral sagittal split osteotomies (BSSO) or mandibular distraction ostoegenesis (MDO). 23 Class II mandibular hypoplasia patients requiring mandibular advancement were randomized into two groups for either BSSO or MDO. Subjective and objective neurosensory evaluations were performed preoperatively and at the following postoperative times: 2 weeks (TBD1), 6 weeks (TBD2), 12 weeks (TBD3), 6 months (TBD4) and 12 months (TBD5). Subjective evaluation included the use of a visual analogue scale (VAS). Objective evaluation included the use of light touch (LT), two-point discrimination (2PD) and pain detection threshold (PD) tests. Intra-operative or postoperative complications were recorded. Using a mixed model, no significant differences were reported in subjective VAS scores and objective LT, 2PD and PD scores between the BSSO and MDO groups over 12 months (p > 0.05). Common postoperative complications included localized wound infection (BSSO = 2, MDO = 6) and condylar resorption (BSSO = 1, MDO = 1).     

Quality and quantity of bone following alveolar distraction osteogenesis in the human mandible

PURPOSE: The purpose of this prospective study on humans were to evaluate (a) the clinical outcome of alveolar distraction osteogenesis for the correction of vertically deficient edentulous mandibular ridges, (b) the clinical outcome of dental implants placed in the distracted areas, and (c) the quality and quantity of the bone that had formed in the distraction gap. MATERIAL AND METHODS: Seven patients presenting vertically deficient edentulous ridges were treated by means of distraction osteogenesis with an intraoral alveolar distractor. Approximately 3 months after consolidation of the distracted segments, 20 ITI solid screw SLA implants were placed in the distracted areas. Three to 4 months later, abutments were connected and prosthetic loading of the implants started. During implant site preparation, bone biopsies were taken at the implant sites with trephine burrs for histologic and histometric analyses. RESULTS: The mean follow-up after the initial prosthetic loading was 18 months (range 12-24 months). The mean bone gain obtained at the end of distraction was 7 mm (range 5-9 mm). The cumulative success rate of implants 2 years after the onset of prosthetic loading was 95%, whereas the survival rate of implants was 100%. The newly formed bone consisted of woven bone reinforced by parallel-fibered bone with bone marrow spaces between the bone trabeculae. The bone area fraction in the distraction region ranged from 21.6% to 57.8% (38.5+/-11.7%). DISCUSSION AND CONCLUSIONS: Results from this study showed that (a) distraction osteogenesis is a reliable technique for the correction of vertically deficient edentulous ridges, (b) the regenerated bone withstood the functional demands of implant loading, (c) survival and success rates of implants placed in the distracted areas were consistent with those of implants placed in native bone, and (d) there is sufficient bone volume and maturity in the distracted region for primary stability of the implant.     

Response of Schwann cells in the inferior alveolar nerve to distraction osteogenesis: an ultrastructural and immunohistochemical study

The biological mechanisms of nerve adaptation to distraction osteogenesis have not yet been elucidated. This study observed response of Schwann cells in the inferior alveolar nerve (IAN) following mandibular lengthening by electron microscopy and immunohistochemistry of S-100 protein, a specific marker of Schwann cells. Unilateral mandibular distraction (10mm elongation) was performed in nine young adult goats. Three animals were sacrificed at 7, 14 and 28 days after completion of distraction, respectively. The distracted IAN specimens and control nerves (from the contralateral sides) were harvested and processed for histological, ultrastructural and immunohistochemical examinations. Wallerian degeneration was observed in the distracted IAN, and Signs of axonal regeneration, as well as many activated Schwann cells were seen in the lengthened nerves. The expression of S-100 protein increased significantly at early stage of distraction osteogenesis, but almost returned to the normal level at 28 days after distraction. This study suggests that Wallerian degeneration caused by mechanical stretching may stimulate Schwann cells to enter a proliferated and activated state. Schwann cells and S-100 protein appear to play crucial roles in axonal regeneration that contributes to nerve adaptation to gradual distraction. Therefore, the IAN injury caused by mandibular gradual distraction was not serious; it seems to recover totally through a complicated repair mechanism.     

下颌骨牵引成骨术对兔下牙槽神经的影响

目的观察牵引成骨术的不同牵引速度和距离对下牙槽神经的影响。方法新西兰白兔16只,以不同的牵引速度和牵引距离组合,随机分成5组。通过肉眼观察、X线片及电生理检查、组织学观察等了解下颌骨成骨及下牙槽神经再生情况。结果以2.0mm/d速度牵引下颌骨会产生骨不连接,以1.5mm/d速度牵引颌骨15mm,虽可获得良好的成骨,但可造成下牙槽神经不可逆性的损伤。结论下颌骨牵引成骨术的速度宜控制在0.5～1.5mm/d范围内;当牵引距离较小时,可适当加大牵引速度以提高牵引效率,当牵引距离较大时,应调小牵引速度,以减小对下牙槽神经的损伤。     

Development of distraction osteogenesis model of the inferior mandibular border and alveolar bone

The aims of this study were to establish an experimental rat model for distraction osteogenesis of the mandible and alveolar bone for the investigation of histologic and radiographic analysis and to develop the device for various distraction models. For osteotomy location and distraction device design, micro-computed tomographic analysis of the structure of rat mandible was performed. Twenty mandibles of Sprawl-Dawley rats were osteotomized based on the analysis, and newly developed custom-made devices were applied with bone screws. After a 5-day latency period, a distraction of 0.2 mm at a single session, and a 4-week consolidation period, animals were killed for histologic samples. The rat distraction osteogenesis model for the inferior mandibular border and alveolar bone was successfully established based on the protocols used in this study. New bone formation occurred at both body and alveolar bones of the mandible by the combination of 2 modes: intramembranous ossification was predominant at the end of distraction period, whereas endochondral ossification was observed at the center of the distraction gap at the end of the 4-week consolidation period. This model can be applied to various conditions related to distraction osteogenesis and provide information for the development of improvements in clinical treatments using distraction osteogenesis.