Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583-0740, USA.
J Periodontol. 2010 Feb;81(2):251-9. doi: 10.1902/jop.2009.090374.
The analysis of biomarkers in gingival crevicular fluid (GCF) may be helpful in forecasting patient vulnerability to future attachment loss. The purpose of this study is to correlate GCF biomarkers of inflammation and bone resorption with subsequent periodontal attachment and bone loss in a longitudinal trial of a matrix metalloproteinase (MMP) inhibitor.
GCF was collected from two periodontal pockets (mean +/- SD: 5.1 +/- 1.0 mm) at baseline and annually in postmenopausal females with moderate to advanced periodontitis undergoing periodontal maintenance every 3 to 4 months during a 2-year double-masked, placebo-controlled, randomized clinical trial of subantimicrobial dose doxycycline (SDD; 20 mg two times a day). Subjects were randomized to SDD (n = 64) or a placebo (n = 64). GCF was analyzed for the inflammation markers interleukin (IL)-1beta (using enzyme-linked immunosorbent assay), total collagenase activity (using hydrolysis of a synthetic octapeptide), and MMP-8 (using a Western blot) and the bone-resorption marker carboxyterminal telopeptide cross-link fragment of type I collagen (ICTP) (using a radioimmunoassay). Generalized estimating equations were used to associate these biomarkers, categorized into tertiles, with subsequent clinical attachment (using an automated disk probe) or interproximal bone loss (using radiography). Odds ratio (OR) values compared highest to lowest tertile groups.
Increases in GCF IL-1beta and MMP-8 during the first year of periodontal maintenance were associated with increased odds of subsequent (year 2) periodontal attachment loss (OR = 1.67; P = 0.01 and OR = 1.50; P = 0.02, respectively) driven by the placebo group. Elevated baseline ICTP was also associated with increased odds of 1- and 2-year loss of alveolar bone density (OR = 1.98; P = 0.0001) in the placebo group, not the SDD group, and a loss of bone height (OR = 1.38; P = 0.06), again driven by the placebo group.
These data support the hypothesis that elevated GCF biomarkers of inflammation and bone resorption from a small number of moderate/deep sites have the potential to identify patients who are vulnerable to progressive periodontitis, and SDD may modify that risk.
分析龈沟液（GCF）中的生物标志物可能有助于预测患者未来发生附着丧失的易感性。本研究的目的是在基质金属蛋白酶（MMP）抑制剂的纵向试验中，将炎症和骨吸收的 GCF 生物标志物与随后的牙周附着和骨丢失相关联。
在一项为期 2 年的、双盲、安慰剂对照、随机临床试验中，对接受每 3-4 个月进行一次牙周维护的、处于围绝经期且患有中重度牙周炎的女性，在 5.1 ± 1.0 mm 的两个牙周袋中收集 GCF，每年收集一次。这些女性被随机分配到 SDD（n = 64）或安慰剂（n = 64）组。分析 GCF 中的炎症标志物白细胞介素（IL）-1β（酶联免疫吸附测定法）、总胶原酶活性（水解合成的八肽）和 MMP-8（Western blot）以及骨吸收标志物 I 型胶原羧基末端肽交联片段（ICTP）（放射免疫测定法）。使用广义估计方程将这些生物标志物（按三分位值分类）与随后的临床附着（使用自动圆盘探针）或近中骨丢失（使用放射照相术）相关联。比较最高和最低三分位组的比值比（OR）值。
在牙周维护的第一年中 GCF IL-1β和 MMP-8 的增加与随后（第 2 年）牙周附着丧失的几率增加相关（OR = 1.67；P = 0.01 和 OR = 1.50；P = 0.02），这主要是由安慰剂组驱动的。基础 ICTP 升高也与安慰剂组而不是 SDD 组的牙槽骨密度 1 年和 2 年丢失的几率增加相关（OR = 1.98；P = 0.0001），并且与骨高度丢失相关（OR = 1.38；P = 0.06），这也是由安慰剂组驱动的。
这些数据支持了这样一种假设，即从少数中重度/深度部位获得的升高的 GCF 炎症和骨吸收生物标志物有可能识别出易患进行性牙周炎的患者，而 SDD 可能会改变这种风险。
