Low-Dose Doxycycline Effects on Osteopenic Bone Loss

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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.