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

描述（由申请人提供）：拔牙部位的牙槽嵴特征为进行性骨丢失，这是一种常见且严重的临床问题，称为残留牙槽嵴吸收（RRR）。RRR的发病机制尚不清楚，但废用（缺乏功能刺激）被广泛认为是一个原因。然而，从未对浸提部位的体内机械环境进行表征。虽然多次拔牙可能会减少对骨骼的咀嚼刺激，但对于单颗牙齿的情况可能并非如此。咀嚼负荷，反映在一个单一的牙齿拔除部位的骨应变，可能会增加，而不是减少，因为1）咬合力不一定减少与一个单一的提取，和2）牙槽骨的结构阻力咬合力受到损害，由于创伤和牙根支持的损失。使用猪模型，我们建议测量和比较拔牙后即刻（基线对照）和6周（实验）（目标1）拔牙部位和对侧非拔牙（对照）部位的颊侧牙槽骨的咀嚼应变。这些研究将提供第一个直接记录的功能力学周围的一个单一的牙齿拔除网站。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结构和重塑。将通过免疫组织化学方法检查细胞特征，包括增殖和破骨细胞生成。将使用实时RT-PCR和蛋白质印迹技术检查骨重建（OPG、RANKL和RANK）和分化（Runx 2）调节因子的表达。总体而言，我们假设，在一个单一的拔牙位点牙槽骨将过度紧张，在咀嚼过程中，由于其受损的结构阻力负荷，这将刺激牙槽骨重建，并导致骨丢失（RRR）。这项研究的特点是在一个单一的牙齿拔除网站的力学环境的直接表征，并澄清功能力学和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。 公共卫生相关性：牙齿脱落，影响数百万人的临床实体，留下进行性骨吸收的残留牙槽嵴。恢复吸收的无牙嵴是具有挑战性和昂贵的。拟议的研究将表征单牙拔除部位牙槽嵴的功能（咀嚼）力学（骨代谢的关键因素），并检查其与骨变化的关系。研究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.