下颌骨放射性骨坏死山羊动物模型的建立

目的建立下颌骨放射性骨坏死(osteoradionecrosis,ORN)山羊动物模型。方法6只成年山羊根据不同照射剂量随机分为3组(15、20、25Gy),照射前收集正常下颌骨影像学及病理学资料,资料收集完成后采用直线加速器按分组剂量对左侧下颌骨行单次照射。照射结束后45d在照射侧行拔牙术,拔牙后每周观察局部及全身情况,拔牙结束后3、6个月行影像学、病理学及骨代谢检查。结果在组织病理学检查上,3组均符合ORN,其严重程度与照射剂量正相关;其中20Gy和25Gy组有典型的临床症状出现;照射前后颌骨影像学检查无明显改变;骨代谢检查发现放疗侧颌骨代谢明显较对侧低。结论成功建立下颌骨ORN山羊动物模型。ORN组织细胞学及颌骨代谢变化先于影像学改变。     

自体骨髓间充质干细胞移植对小型猪下颌骨放射性骨坏死的预防作用

目的：观察和分析自体骨髓间充质干细胞（ bone marrow mesenchymal stem cells,BMMSCs）静脉输注移植是否对小型猪下颌骨放射性骨坏死（ osteoradionecrosis,ORN）有预防作用。方法照射前1个月分离培养扩增BMMSCs,在照射后不同时点实验组进行自体BMMSCs静脉输注移植,对照组静脉输注同体积不含细胞的细胞培养液。照射2个月后拔除左侧下颌第一恒磨牙,通过肉眼、CT以及组织病理学观察小型猪动物模型下颌骨是否发生ORN。结果照射2个月拔牙创伤后,两组动物均出现了组织水肿、皮肤溃烂、骨质破坏等。5个月后实验组动物皮肤愈合,随后CT显示破坏骨质修复,组织病理学显示为接近正常的骨组织,而对照组动物下颌骨仍呈典型ORN表现。结论自体BMMSCs移植对下颌骨ORN有一定的预防作用,其预防机制尚有待进一步研究。     

下颌骨放射性骨坏死骨组织的电镜观察

目的在建立小型猪下颌骨放射性骨坏死动物模型基础上,应用电镜技术研究下颌骨放射性骨坏死形成、发展的超微结构动态变化过程。方法对6只小型猪右侧下颌骨进行25 Gy和28 Gy一次性照射,建立小型猪右侧下颌骨放射性骨坏死动物模型,分别于照射结束后3、4、5个月切取右侧下颌骨放射性骨坏死部位死骨,制备标本,进行电镜检查分析。结果照射后的早期骨胶原纤维即受到破坏,骨细胞先出现细胞膜破坏,随后胞质出现空泡,细胞器裂解,最后出现核变化。大剂量照射后骨细胞的破坏出现早而重,并且加速了骨细胞的裂解、死亡。结论骨细胞细胞膜及细胞质较细胞核对放射线更为敏感,照射后骨细胞死亡过程首先发生在细胞膜及细胞质内,与以往认为细胞核损伤在先的观点不同。     

头颈部放射治疗后拔牙与放射性颌骨骨髓炎关系的临床分析

目的探讨牙拔除术对头颈部放射治疗后患者发生放射性颌骨骨髓炎（osteoradionecrosis,ORN）的影响。方法收集83例头颈部恶性肿瘤放疗后经x线诊断ORN的需拔牙患者,拔牙前给予口服抗生素2d,微创拔牙,术后继续口服抗生素5d,3个月拔牙创不愈合者诊断为ORN。结果83例患者放疗后因智齿冠周炎、急性牙髓炎、残根残冠、根尖周炎等,共拔除182颗患牙,其中8例出现ORN。放疗剂量不同导致放疗后拔牙发生ORN的差异有统计学意义（x^2=5．004,P=0．025）,高剂量患者（70～80Gy）拔牙后ORN炎发生率25．00％,明显高于低剂量患者（50—70Gy）的发生率4．76％。放疗后拔牙时间（X2=0,P=I．000）、一次性拔牙总数目（x2=0,P=1．000）对放疗后拔牙发生ORN的差异无统计学意义。结论放射剂量是诱发ORN的主要原因,放疗前拔除患牙、放疗后定期检查口腔,防治牙周、牙体疾病是预防ORN的主要手段。     

α2巨球蛋白对大鼠下颌骨放射性骨坏死的预防作用

目的: 观察和分析在X线照射前于大鼠下颌骨体局部注射α2巨球蛋白（alpha2-macroglobulin, α2M）是否对大鼠下颌骨放射性骨坏死（osteoradionecrosis,ORN）具有预防作用。 方法: 健康SD雄性大鼠18只,随机分为3组,每组6只。其中A组为空白对照组,B组为单纯X线照射组,C组为X线照射前左侧下颌骨局部注射α2M组。大鼠均经麻醉后使用3D打印装置固定,B、C组使用X线生物学辐照器对其左侧下颌骨进行精准照射,每天7 Gy,连续照射5 d;A组假照射;C组在第1次X线照射前30 min于大鼠左侧下颌骨体部骨膜下局部注射0.5 mL 2000 mg/L的α2M,A、B组在同样部位注射等量无菌生理盐水（normal saline,NS）。照射完成后第7天,拔除大鼠左侧下颌3颗磨牙。照射完成后第28天处死所有大鼠,从大体、影像学、病理学等方面系统评估各组大鼠的放射损伤。采用SPSS 13.0软件包对数据进行统计学分析。 结果: B组5只大鼠大体上体重明显减轻、照射区黏膜重度溃疡、受照侧颊部脱毛、咬合关系紊乱;影像学显示明显的骨质缺损;病理观察发现照射区皮质骨空白骨陷窝增多、死骨形成、纤维增生等骨坏死典型症状,证实发生下颌骨ORN,发生率为5/6;与B组相比,C组大鼠大体上仅表现为轻度体重下降及照射区脱毛,影像学上未见明显骨质缺损,病理观察仅见骨髓腔内轻微炎症,皮质骨无明显破坏,骨陷窝空虚率较B组显著降低（P<0.001）;C组大鼠下颌骨ORN发生率为零。 结论: X线照射前注射α2M对下颌骨ORN的发生具有较好的预防作用。     

兔下颌骨放射性骨坏死模型的建立及评估

目的 建立兔下颌骨放射性骨坏死动物模型,并通过大体观察、单光子发射计算机体层摄影（SPECT）、显微CT及组织病理学方法对该模型进行评估。方法 将24只新西兰兔随机分为对照组和低、中、高3个剂量组,根据生物学等效公式,以低分割多次照射法,使用直线加速器对各组动物的左侧下颌区分别进行0、8.0、8.9和9.7 Gy照射,共5次。45 d后,拔除所有动物左侧下颌磨牙,3个月后,进行大体观察、SPECT、显微CT及组织病理学检查,采用SPSS17.0软件包对数据进行统计学处理。结果 高剂量组动物死亡率较高。高、中剂量组出现照射区皮肤脱毛及照射侧拔牙创不愈合、下颌骨死骨形成并暴露;低剂量组脱毛不明显、拔牙创形成完整黏膜覆盖。组织学观察显示,高、中剂量组下颌骨有死骨形成及骨髓腔纤维化改变,低剂量组主要表现为髓腔炎症。SPECT显示,高、中剂量组代谢率较对照组显著降低。Micro-CT显示,高、中剂量组有死骨分离及骨皮质破坏,BV/TV、Tb.Th、Tb.N值下降,Tb.Sp值增加。结论 以 8.9 Gy剂量对兔下颌区进行分割照射并在照射后拔牙,可成功建立下颌骨放射性骨坏死模型,在各项指标中均有明显放射性骨坏死表现,可重复性好,是研究下颌骨放射性骨坏死较为理想的动物模型。     

放射照射后牵张下颌骨成骨犬实验动物模型的建立

目的：建立放射照射后牵张下颌骨成骨犬实验动物模型。方法：选取成年中国犬12只,实验组10只以60 Co 颊舌向照射下颌骨后部标定区域,照射方法为22．8 Gy、5．7 Gy／次,共4次（生物等效剂量为50 Gy／25次）。对照组2只不照射。照射完成后3个月,在动物下颌第五和第六臼齿间行骨皮质切开术,植入骨牵张器,经过1周的延迟期,2次／d,每次0．5 mm 的速率连续牵张下颌骨10 d,然后固定8周。处死动物,以放射学,组织学和 SPECT 方法对牵张区新骨进行检查,对下牙槽神经进行组织学检查。结果：除实验组1只动物因麻醉意外死亡,其他动物都完成了实验。实验组和对照组新骨形成无明显差异。SPECT 显示实验组成骨活跃。观察到下牙槽神经修复性组织学变化。结论：放射照射后牵张犬下颌骨可形成新骨。     

补肾壮骨合剂对骨质疏松犬拔牙后骨愈合影响研究

目的    探讨补肾壮骨合剂对骨质疏松犬拔牙后骨愈合的影响。方法    选择3岁龄杂种雌性成年犬9只,随机均分为对照组、西药组和中药组。手术切除9只犬的双侧卵巢（去势术）,检测腰椎骨密度（BMD）以确定建立骨质疏松模型。各组犬在去势术后3个月拔除两侧下颌前磨牙,拔牙术后第3天开始骨质疏松治疗,中药组灌服补肾壮骨合剂溶液,西药组服用戊酸雌二醇片（补佳乐）,对照组不进行任何治疗。在去势术前、去势术后3个月以及拔牙后3个月分别检测各组犬的腰椎BMD和下颌骨BMD,并于拔牙术后1、2、3个月切取下颌骨进行组织形态学观察。结果    拔牙后3个月,中药组、西药组的腰椎和下颌骨BMD较骨质疏松治疗前显著提高,与去势术前比较差异均无统计学意义（均P > 0.05）;而对照组拔牙后3个月的腰椎和下颌骨 BMD未见明显改善,仍明显低于去势术前（P < 0.05）。下颌骨组织形态学观察显示,拔牙后1个月,对照组、西药组拔牙创愈合的新骨小梁走行不规则;中药组新生骨小梁排列成网状。拔牙后2个月,对照组局部骨小梁结构较稀疏;西药组新生骨小梁粗壮,排列较整齐;中药组新生骨骨小梁呈网状结构,骨小梁数量多、粗壮。拔牙后3个月,对照组拔牙创骨小梁结构比较致密,间隙较小;西药组新生骨组织与原骨组织大致融合一体;中药组新骨组织与原骨组织结构基本一致。结论    补肾壮骨合剂治疗可使骨质疏松犬拔牙创周围松质骨区骨量明显增加,有助于骨改建,有效促进拔牙创骨愈合。     

小型猪一侧失牙及义齿修复后颞下颌关节的组织病理学观察

目的：观察一侧失牙及义齿修复对小型猪颞下颌关节（temporomandibular joint，TMJ）组织结构的影响。方法：11只小型猪随机分为空白组（2只）、拔牙组（4只）、修复组（5只），将拔牙组和修复组左侧后牙全部拔除，修复组并于拔牙后3个月进行义齿修复。小型猪一侧失牙6个月时处死，解剖TMJ并制作光镜（HE染色）和透射电镜标本，观察其组织结构改变。结果：拔牙组和修复组小型猪双侧TMJ均发生不同程度的退行性改变。髁突软骨表面带玻璃样变性、断裂、剥脱；肥大带下陷成乳突样，软骨细胞成簇；骨小梁破坏呈蚕蚀状。关节盘胶原纤维变性、紊乱、断裂，盘后组织出现明显软骨化生。髁突软骨瘀斑、凹陷、剥脱的超微病理特征分别是细胞变性、凋亡、坏死。结论：长期一侧失牙可导致双侧TMJ退行性变，及时义齿修复可减轻TMJ的病理损伤。     

单一剂量单侧腮腺放射损伤对双侧腮腺结构和功能的影响

目的 研究单一大剂量射线照射单侧小型猪腮腺对双侧腮腺结构和功能影响。方法 14只小型猪一侧腮腺用直线加速分别给予15 Gy（7只）和20 Gy（7只）离子射线照射,4只做为空白对照。分别在放射前,放射后4周和16周观察腮腺唾液流率、腺体重量、腺泡面积和组织学变化。结果 4周时,15 Gy和20 Gy照射后放射侧腮腺重量下降达50%;15 Gy照射后放射侧腮腺唾液流率无明显下降,20 Gy照射后放射侧腮腺唾液流率减少约50％。16周时,15 Gy和20 Gy照射后放射侧腮腺重量下降达50%,组织学明显改变,照射后放射侧腮腺流率分别下降约60%及80%。非放射侧腮腺重量及形态均无明显变化,但20 Gy照射后16周时非放射侧腮腺唾液流率明显下降。结论 单一剂量照射后腮腺结构的改变相对唾液流率下降发生较早,唾液流率减少与腺泡面积的减少不完全成正相关。非照射侧腮腺形态变化不明显,但唾液流率明显下降。     

Osteoradionecrosis of the jaws: clinical characteristics and relation to the field of irradiation.

PURPOSE: This study focuses on the clinical characteristics of patients with osteoradionecrosis (ORN) of the jaws and on the relation between the extent of the ORN and the field of irradiation. PATIENTS AND METHODS: The study group consisted of 80 patients referred for treatment of ORN. Charts of the extent of ORN, based on panoramic radiographs, were drawn by the clinical investigator and compared with charts of the field of irradiation drawn by the oncologists. Also recorded was diagnosis of the lesion, stage, location, treatment schedule, and period and dose of irradiation. Also documented were various potential initiating factors for ORN. RESULTS: Smoking habits of ORN patients were similar to those of other patients with head and neck cancer. A new primary tumor or a recurrence was diagnosed in 10% of the patients at the time of ORN. Only 3 patients had received accumulated doses of less than 60 Gy. More than half of the cases were initiated by removal of teeth; however, one third occurred spontaneously. ORN developed within the first 3 years in 74%; but ORN can emerge on a traumatic basis for an infinite number of years after radiation therapy. Widespread ORN may be symptomless apart from a discrete dehiscense of the oral mucosa. The predilection site for ORN is the mandibular molar region. All cases of ORN but 1 were found in the field of radiation. CONCLUSION: Because many ORN case are symptomless, more focus on mucosal dehiscence in the follow-up after radiation therapy is advocated in an effort to detect ORN at an early stage. The consequence of practically all ORN cases being located in the field of irradiation, together with tooth removal frequently being the initiating factor, should lead to a more aggressive preirradiation approach to dental pathology located within the field of radiation.     

颌骨放射性骨坏死相关危险因素分析

目的：评估头颈肿瘤患者颌骨放射性骨坏死的相关发病因素。方法：回顾性分析79例放射性颌骨骨坏死的临床资料,包括原发肿瘤类型与部位、放疗剂量,牙及牙周状况,手术类型,是否拔牙,发病时间,主要症状,影像学表现与治疗等。结果：约一半的放射性颌骨骨坏死患者原发肿瘤是鼻咽癌。86%的骨坏死患者在放疗后5年内就诊。虽然60.8%的病例放疗剂量大于60Gy,但81%的口腔鳞癌病人放疗剂量小于60Gy。放疗后病人平均患龋牙数（13.5颗）明显高于放疗前（5.6颗）（P〈0.01）。放疗后拔牙的患者中14.3%发生射性颌骨骨坏死。结论：颌骨放射性骨坏死的发生与放射损伤外,亦与患龋牙多及放疗后拔牙等因素有密切关系。     

Cause and occurrence timing of osteoradionecrosis of the jaw: a retrospective study focusing on prophylactic tooth extraction

Purpose

This retrospective study aimed to analyze the relationship between tooth extraction and osteoradionecrosis (ORN) occurrence. The irradiation field, dose, and time interval between radiotherapy (RT) and ORN were reviewed. We also discuss appropriate guidelines for prophylactic tooth extraction.

Methods

A total of 33 patients treated for grade ≥2 (clinical) ORN in our department from 2002 to 2014 were enrolled. The following epidemiological data were retrospectively gathered: age, sex, histological diagnosis, primary tumor sites, radiation dose, chemotherapy, site of ORN, relationship between tooth extraction and ORN occurrence, and time interval between tooth extraction and the initiation or end of RT.

Results

Twenty-one percent of ORN cases resulted from tooth extraction. The most common site of ORN (82 %) was the mandibular molar region. About half of ORN cases (49 %) occurred within 2 years after RT. All patients who received tooth extraction after RT developed ORN (100 %) independently of time interval between tooth extraction and the end of RT (median interval, 37.5 months; range, 27–120 months). In contrast, only 50 % of patients who received tooth extraction before RT developed ORN. There may have been an association between the irradiation field and the site of ORN development

Conclusions

ORN occurrence due to tooth extraction was 21 %. Occurrence timing of ORN did not depend on time interval between tooth extraction and the end of RT. The irradiation field is certainly related to the site of ORN; therefore, prophylactic tooth extraction should be performed in consideration of the proposed radiation field and dose.

     

Implant osseointegration in the irradiated mandible. A comparative study in dogs with a microradiographic and histologic assessment

This research focuses on the effects of radiotherapy on the osseointegration of dental implants placed before or after radiotherapy in 11 male beagles. After the extraction of all mandibular premolars 1st and 2nd molars, three dogs were implanted without radiotherapy (Control group), four dogs were irradiated 4 weeks after implantation (IrA group) and four dogs were irradiated 8 weeks before implantation (IrB group). Eight implants were placed in each dog, in an alternating pattern: four nonsubmerged ITI Bonefit titanium plasma spray-coated and four submerged Steri-Oss hydroxyapatite-coated. The irradiated dogs received 4.3 Gy daily for 10 days. Two different fluorescent markers were administered at the time of implantation and of irradiation. The dogs were sacrificed 6 months after implantation, i.e. 5 months after radiotherapy for the IrA group and 8 months for the IrB group. Each mandible was submitted to histological and microradiographic analysis. Bone formation occurred around 85 of the 88 implants and consisted mostly of the successive deposit of woven and lamellar bone. Both irradiated groups showed obvious bone remodeling in alveolar bone as well as in the basilar part of the mandible. Nevertheless, in the IrA group, the resorption phenomena predominated over osteogenesis. The balance between these two opposite processes seemed to be restored 8 months after the end of radiotherapy (IrB group). In spite of focal lesions of radiation-specific bone destruction emphasized in some irradiated dogs, we conclude from our results that osseointegration of dental implants is possible in irradiated bone tissue.     

Effects of pentoxifylline and tocopherol on an osteoradionecrosis animal model

PurposeOsteoradionecrosis (ORN) is known to be a refractory disease in the oral and maxillofacial field. The purpose of this study was to examine the effects of pentoxifylline (PTX) and tocopherol (TP) on an ORN animal model focused on bone healing.Materials and methodsA total of 48 Sprague–Dawley rats were used: 40 received a single irradiation dose of 35 Gy on the left mandible, and eight were used as the nonirradiated control group. The rats received PTX (T1, C1), TP (T2, C2), a combination of PTX and TP (T3, C3), or normal saline (T4, C4). Three weeks after irradiation, the mandibular posterior teeth were extracted. The rats were sacrificed 4 weeks after extraction.ResultsIn the T3 group, bone volume/tissue volume was 19.62 ± 16.03 (%), bone mineral density was as 0.31 ± 0.16 (g/cm³) in the micro-CT analysis, which were higher than that of other groups (p = 0.025, p = 0.012, respectively). In the histological analysis, bone regeneration was the most prominent in the T3 group. The ratio of empty lacunae was the highest in the T4 group, 68.77 ± 15.47 (%, p = 0.004). Immunohistochemistry showed that the expression of TNF-α was relatively lower in the T3 than in the T4 or T2 groups. The RT-qPCR showed the expression level of PECAM, VEGF-A, and osteocalcin was more than twofold as high as in the T3 group compared to the other groups.ConclusionThe combination of PTX and TP appears to promote angiogenesis and osteogenesis in a rat ORN model. Therefore, PTX and TP might be useful in the treatment and prevention of ORN.