Low-Dose Doxycycline Effects on Osteopenic Bone Loss

描述（由申请人提供）：本申请是标题为“低剂量强力霉素对骨质减少性骨丢失的影响”的R 01 DE 12872 -05的竞争性延续。“对于目前资助的赠款，128名绝经后（PM）骨质疏松症妇女慢性牙周炎随机接受亚抗菌剂量（低剂量; LDD）强力霉素或安慰剂对照在为期两年的随机临床试验。这项试验正在进行中，正在测试LDD将减少牙周组织和骨骼组织（股骨颈和腰椎）中的骨丢失的假设。除了骨质流失，心血管疾病（CVD）是绝经后的另一种临床后遗症，最近的证据表明，全身炎症在CVD发病机制中起着重要作用。重要的是，我们最近证明LDD减少了急性冠状动脉综合征患者全身炎症的生物标志物。在我们2004年3月的会议之后，NIDCR和数据与安全监测委员会批准了一份补充同意书;这些签署的同意书允许我们检查血清炎症生物标志物对LDD的反应。然而，没有资金进行这些额外的检测;因此，我们正在申请这种竞争性延续。我们的临床试验目前正在基线、1年和2年访视时收集血清，并测量骨吸收/形成的血清生物标志物。该应用的假设是LDD可以减少PM女性中与CVD风险相关的全身性炎症和MMP的生物标志物。这一假设将通过追求以下具体目标进行测试：确定LDD治疗，在PM骨质减少的妇女与慢性牙周炎，有益地改变血清生物标志物的全身炎症和CVD（C-反应蛋白，IL-6，髓过氧化物酶，MMP-2和MMP-9）的患者已经参加了我们目前的临床试验。本研究不需要采集额外的血清，这将使我们能够扩大我们目前资助的R 01的意义。这项工作是重要的，因为，如果LDD最终被发现，以减少更年期的两个主要并发症（即骨质疏松症和心血管疾病的发病率增加）的严重程度，LDD可以提供一种替代激素替代疗法的PM妇女。这项工作与公共卫生有关，因为LDD可能提供安全有效的治疗方法，以减少与更年期相关的并发症。减少骨丢失和CVD发病率将代表显著的公共卫生改善。

DESCRIPTION (provided by applicant): This application is a competing continuation of R01DE12872-05 entitled, "Low-Dose Doxycycline Effects on Osteopenic Bone Loss." For the currently-funded grant, 128 postmenopausal (PM) osteopenic women with chronic periodontitis were randomized to receive either subantimicrobial dose (low-dose; LDD) doxycycline or a placebo control in a two-year randomized clinical trial. This trial is ongoing and is testing the hypothesis that LDD will reduce bone loss in the periodontium and skeletal tissues (femoral neck and lumber spine). In addition to bone loss, cardiovascular disease (CVD) is an additional clinical sequelae of menopause and recent evidence suggests that systemic inflammation plays an important role in CVD pathogenesis. Importantly, we recently demonstrated that LDD reduces biomarkers of systemic inflammation in acute coronary syndromes patients. The NIDCR and Data and Safety Monitoring Board approved an addendum consent form subsequent to our March 2004 meeting; these signed consent forms give us permission to examine serum inflammatory biomarkers in response to LDD. However, no funds are available to conduct these additional assays; hence, we are applying for this competing continuation. Serum is currently being collected in our clinical trial at baseline, one-year and two-year visits and serum biomarkers of bone resorption/formation are being measured. The hypothesis for this application is that LDD can reduce biomarkers of systemic inflammation and MMPs associated with CVD risk in PM women. This hypothesis will be tested by pursuing the following specific aim: determine whether LDD therapy, in PM osteopenic women with chronic periodontitis, beneficially alters serum biomarkers of systemic inflammation and CVD (C-reactive protein, IL-6, myeloperoxidase, MMP-2 and MMP-9) in patients already enrolled in our current clinical trial. No additional serum will need to be collected for this study which will enable us to expand the significance of our currently-funded R01. This work is significant because, if LDD ultimately is found to reduce the severity of two major complications of menopause (namely, osteoporosis and increased incidence of CVD), LDD could provide an alternative to hormone replacement therapy in PM women. This work is relevant to public health as LDD may provide a safe and effective therapy to reduce complications associated with menopause. Reduced bone loss and CVD incidence would represent significant public health improvements.