双膦酸盐相关性颌骨坏死

双膦酸盐类（BPs）药物是一种强有力的骨吸收抑制剂,已广泛应用于临床治疗中。近年来,有关双膦酸盐相关性骨坏死（BRONJ）的报道日渐增多,该病临床上以骨面裸露、死骨形成、疼痛、口臭等为特征。由于目前发病机理不明确,临床上尚无完全有效的治疗方法,因此BRONJ的预防十分重要。本文就BRONJ的发病机制、危险因素、临床特征、治疗预后等方面的研究现状进行阐述,以期为临床提供帮助。     

双膦酸盐致颌骨坏死的研究进展

双膦酸盐在临床上使用已有十余年的时间,对骨质疏松和骨源性恶性肿瘤有很好的治疗效果。但其并发症双膦酸盐相关性颌骨坏死(bisphosphonate-associated osteonecrosis of the jaw,BP-ONJ)一直困扰着临床医生。各国学者对其进行了深入的研究和探讨。该文就其最新的研究进展做一综述。     

25例双膦酸盐相关颌骨坏死病例分析

目的总结双膦酸盐相关颌骨坏死(bisphosphonate-related osteonecrosis of the jaw,BRONJ)病例的临床及X线特点。方法对25例临床诊断为BRONJ患者的临床和X线资料进行回顾性分析。结果 25例患者中女性12例,男性13例,年龄35~81岁;其中23例曾患恶性肿瘤,另2例为骨质疏松症。临床表现多为患区反复肿痛、流脓和牙齿松动。25例共存在31个病灶。所有患者的X线表现均有颌骨密度改变。其中9处颌骨病变仅表现为骨密度改变而未形成死骨,为早期病变;其它X线表现包括死骨形成(22个)、牙槽窝不愈(17个)和骨膜反应(10个)。结论 BRONJ早期X线表现为颌骨密度改变和线状骨膜反应,晚期可形成死骨,常累及多个象限。     

双膦酸盐性颌骨坏死的研究进展

近年来,不断有患者接受双膦酸盐类药物治疗后发生颌骨坏死的报道,包括目前在临床广泛使用的抗骨质疏松药福善美及抗恶性肿瘤骨转移药物阿可达和择泰,引起临床医生的高度关注。作者就有关双膦酸盐类药物引起颌骨坏死的临床表现、诊断、治疗、预防,以及可能的发病机制做一综述。     

双膦酸盐相关性颌骨坏死1例报告及文献复习

双膦酸盐类药物被广泛用于治疗骨质疏松、恶性肿瘤骨转移等相关的骨骼疾病,引起颌骨骨坏死是其严重的并发症。这种并发症或自然发生,或发生于简单牙槽外科手术后。本文报告1例静脉使用双膦酸盐类药物唑来膦酸(zoledronic acid)致上颌骨骨坏死病例,并结合文献,对双膦酸盐相关性颌骨坏死的发病机制、临床表现、预防和治疗进行讨论。     

双膦酸盐性颌骨坏死：病例报告及文献复习

双膦酸盐类药物临床用于治疗骨质疏松症、变形性骨炎和其他代谢性骨病、多发性骨髓瘤以及与肿瘤转移相关的骨骼疾病。该类药物通过抑制破骨细胞介导的骨吸收而产生临床治疗作用。然而,双膦酸盐类药物,尤其是静脉用双膦酸盐类药物有致颌骨骨坏死的危险。目前,国内尚未有该类药物致下颌骨坏死的报道。作者报告1例口服双膦酸盐类药物阿仑膦酸钠（Alendronate,商品名福善美,Fosamax）致下颌骨骨坏死病例,并结合文献对双膦酸盐性颌骨坏死的发病机制、临床表现及其预防和治疗进行讨论。     

双膦酸盐相关性颌骨坏死1例报道及文献回顾

随着双膦酸盐类药物在骨质疏松、恶性肿瘤骨转移等方面的广泛应用,有部分患者会发生颌骨坏死的报道,逐渐引起口腔医生的关注。本文报道1例我院双膦酸盐类药物引起颌骨坏死的病例,并结合文献讨论双膦酸盐类药物性颌骨坏死(BRONJ)的发病机制、诊断、预防及治疗方法。     

小鼠双膦酸盐相关性颌骨坏死建模的研究进展

随着双膦酸盐药物的广泛应用,双膦酸盐相关性颌骨坏死(bisphosphonate related osteonecrosis of the jaw,BRONJ)的病例报道日益增多.动物模型是研究该病发病机制及防治策略的有效途径.小鼠具有饲养周期短、便于进行基因水平的调控等优势,因此利用小鼠构建BRONJ模型的报道逐渐增...     

双膦酸盐类药物相关性颌骨坏死临床研究

目的：了解双膦酸盐类药物相关性颌骨坏死（bisphosphonate?related osteonecrosis of the jaw ,BRONJ）的发病机制,探讨其诊断、临床表现、治疗和预防方法。方法对近两年收治的4例BRONJ患者资料进行回顾分析,结合国内外相关文献报道进行临床总结。结果报告的4例患者均有使用双膦酸盐类药物史,临床主要表现为患区反复疼痛、流脓,骨暴露及死骨形成。3例患者接受手术,同时抗生素对症治疗,其中1例术前病情最重的患者出院后半年内曾有小范围感染灶,口服抗生素控制,其余患者均无明显感染及复发。结论恰当的手术治疗对BRONJ可控制感染,缓解症状,使病情趋于静止。     

Alveolar bone and the bisphosphonates

Bisphosphonate associated osteonecrosis of the jaws (ONJ) usually commences at the alveolus. Comparison is made between the structure and function of long bones and alveolar bone and the differing susceptibilities of the bisphosphonates at these different sites are explored. Current concepts of the causation of ONJ are discussed. The clinical implications of these findings to dentists managing periodontal conditions are presented.     

A novel animal model to study non‐spontaneous bisphosphonates osteonecrosis of jaw

J Oral Pathol Med (2010) 39 : 390–396 The aim of this study was to evaluate a novel animal model of bisphosphonates‐associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm‐diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach.     

Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws

Objectives:  To determine the extent to which clinical and radiographic features of bisphosphonate-associated osteonecrosis of the jaw (BONJ) are correlated.
Design:  Retrospective case review.
Methods:  The records of 39 patients diagnosed with BONJ and examined by panoramic radiography were retrospectively evaluated. The arches were divided into sextants ( n  = 234) and evaluated for the following signs: sclerosis, surface irregularity, sockets, fragmentation and lysis.
Main outcome measures:  The McNemar, Kruskall–Wallis and equivalency tests were performed to analyze the association between clinical and radiographic signs and BONJ severity.
Results:  Sixty-two out of 234 sextants were abnormal by clinical criteria and 61 out of 234 sextants demonstrated at least one radiographic abnormality. There was agreement between clinical and radiographic detection in 41 sextants. The data showed equivalency between BONJ diagnosis and both sclerosis and surface irregularity. The correlation between number of clinical sites and any radiographic finding was significant in the maxilla ( P  < 0.001) but not in the mandible ( P  = 0.178). The total number of radiographic signs per patient increased with BONJ stage.
Conclusion:  Focal panoramic radiographic findings of sclerosis and surface irregularity correlate with clinical sites of BONJ. This may be a useful and reliable tool to detect early changes of BONJ or to confirm a clinical diagnosis.     

Histological findings on jaw osteonecrosis associated with bisphosphonates (BONJ) or with radiotherapy (ORN) in humans

Abstract

Objective. To describe the histological features of bone tissue harvested from patients affected by jaw osteonecrosis associated with bisphoshponates (BONJ) or with radiotherapy (ORN), in undecalcified ground sections. Materials and methods. Sixteen bone tissue samples from 14 patients with BONJ and two patients with ORN were processed in order to obtain both ground, undecalcified sections and decalcified sections. The sections underwent histometric and morphometric analysis. Results. Bone tissue samples obtained from patients with BONJ or ORN of the jaws shared some histological characteristics. Common histological features included the loss of bone architecture, the absence of a proper Haversian system and proper marrow spaces, the presence of necrotic spots of non-mineralized tissue, areas of empty osteocytic lacunae next to areas of hypercellularity, the presence of resorption pits with rare osteoclast-like cells and the presence of bacteria and of an inflammatory infiltrate. A violet rib of tissue characterized by large resorption pits facing was frequently observed between the mineralized bone and the inflammatory infiltrate. Conclusions. The histological features of BONJ and ORN are similar and resemble those of osteomyelitis. Even though it is not clear whether infection is the cause or consequence of bone exposure, inflammatory cells, bacteria or their products may have a massive, direct lytic effect on bone tissue challenged by bisphosphonates.     

Avascular jaw osteonecrosis in association with cancer chemotherapy: series of 10 cases

BACKGROUND: We present a series of 10 patients with osteonecrosis of the jaws (ONJ) that appeared following cancer chemotherapy. MATERIAL AND METHODS: Of the 10 cases with ONJ, six had bone metastases from breast cancers and the other four had multiple myeloma. We analysed the location of bone metastases, as well as the characteristics of the ONJ, and the drugs with which they had been treated for their bone metastases. RESULTS: Of the 10 patients, all had ONJ in the mandible; 50% also had maxillary involvement. The average number of areas of painful exposed was 2.1 per patient (range 1-5). In seven patients a tooth extraction preceded the onset of ONJ. Two patients developed oroantral communications and another a cutaneous fistula to the neck with suppuration. In all the 10 patients the histopatholological diagnosis was of chronic osteomyelitis without evidence of metastatic disease to the jaws. All the patients had received treatment for their malignant bone disease with bisphosphonates. These were the only drugs that all patients had received. CONCLUSION: ONJ appears to have a relationship with the use of bisphosphonates.