Single-tooth extraction site bone loss ---- functional disuse or overuse?

描述(申请人提供)：拔牙部位的牙槽骨以进行性骨丢失为特征，这是一种常见和严重的临床问题，称为残余牙槽骨吸收(RRR)。RRR的发病机制尚不清楚，但停用(缺乏功能刺激)已被广泛认为是原因之一。然而，提取部位的体内机械环境从未被描述过。虽然多次拔牙可能会减少对骨骼的咀嚼刺激，但单牙拔牙可能就不是这样了。由于1)一次拔牙不一定会降低咬合力，2)牙槽骨对咬合力的结构抵抗力会因创伤和牙根支持的丧失而受损，因此，单牙拔除部位的骨应变所反映的咀嚼负荷可能会增加而不是减少。利用猪模型，我们建议在拔牙后即刻(基线对照)和6周(实验1)测量和比较拔牙部位和对侧非拔牙部位口腔牙槽骨的咀嚼应变。这些研究将首次直接记录单牙拔除部位周围的功能机制。此外，我们将研究拔牙后牙槽骨的变化，与对照侧相比，并与机械应变相关(目标2)。将使用组织形态计量学方法检查牙槽骨的结构和重塑。包括增殖和破骨细胞生成在内的细胞特征将通过免疫组织化学方法进行检测。将使用实时RT-PCR和Western印迹技术检测骨重塑(OPG、RANKL和RANK)和分化(Runx2)调节因子的表达。总体而言，我们假设单个拔牙部位的牙槽骨在咀嚼过程中会因其对载荷的结构性抵抗而过度紧张，这将刺激牙槽骨重塑并导致骨丢失(RRR)。这项研究的特点是直接描述了单牙拔除部位的力学环境，并阐明了功能力学和RRR之间的关系。这项研究的结果将有助于指导未来对这种影响数百万人的严重临床实体的发病机制和预防的研究进程。 公共卫生相关性：牙齿缺失是一种影响数百万人的临床实体，在进行性骨吸收过程中会留下残留的牙槽骨。修复吸收的无牙牙列是一项具有挑战性且成本高昂的任务。这项拟议的研究将描述功能(咀嚼)力学，这是骨代谢的关键因素，在单牙拔除位置的牙槽骨槽骨，并检查其与骨变化的关系。这一结果将指导研究人员和临床医生寻求有效的预防策略。

DESCRIPTION (provided by applicant): The alveolar ridge at an extraction site is characterized by progressive bone loss, a common and serious clinical problem termed residual ridge resorption (RRR). The pathogenesis of RRR is not clear, but disuse (lack of functional stimulation) has been widely considered a cause. The in vivo mechanical environment of the extraction site, however, has never been characterized. While it is likely true that multiple extractions reduce masticatory stimulation to the bone, this may not be the case for a single-tooth extraction. Masticatory loading, as reflected by bone strain at a single-tooth extraction site, may be increased rather than decreased because 1) occlusal force is not necessarily reduced with a single extraction, and 2) the structural resistance of alveolar bone to occlusal force is compromised due to trauma and the loss of tooth root support. Using a pig model, we propose to measure and compare masticatory strain at the buccal alveolar bone of an extraction site and a contralateral non-extraction (control) site immediately (baseline control) and 6 weeks (experimental) after the extraction (Aim 1). These studies will provide the first direct recordings of functional mechanics surrounding a single-tooth extraction site. Further, we will investigate the post-extraction change of the alveolar bone as compared to the control side and correlated with mechanical strains (Aim 2). Alveolar bone structure and remodeling will be examined using histomorphometric methods. Cellular features including proliferation and osteoclastogenesis will be examined by immunohistochemical methods. Expression of bone remodeling (OPG, RANKL and RANK) and differentiation (Runx2) regulators will be examined using real-time RT-PCR and Western blot techniques. Overall, we hypothesize that alveolar bone at a single-extraction site will be overstrained during mastication due to its compromised structural resistance to loading, which will stimulate alveolar bone remodeling and lead to bone loss (RRR). This study features a direct characterization of the mechanical environment at a single-tooth extraction site and clarifies the relationship between functional mechanics and RRR. The findings of this study will contribute in directing the course of future research on the pathogenesis and prevention of this severe clinical entity affecting millions. Public Health Relevance: Tooth loss, a clinical entity affecting millions, leaves a residual alveolar ridge undergoing progressive bone resorption. Restoring an absorbed edentulous ridge is challenging and costly. The proposed research will characterize functional (masticatory) mechanics, a critical factor for bone metabolism, at a single-tooth extraction site alveolar ridge and examine its relationship with bone change. The results will guide researchers and clinicians in seeking effective preventive strategies for this disease.