Effects of Low-Dose Doxycycline on Oral Bone Loss

The primary purpose of this clinical trial is to determine whether low-dose doxycycline
(LDD) can reduce alveolar bone density loss in postmenopausal osteopenic women with
periodontitis and not on hormone replacement therapy (i.e., estrogen deficient). The effects
of LDD on alveolar bone height loss, progressive periodontal attachment loss, systemic bone
mineral density, gingival crevicular fluid biochemical markers of collagen degradation and
bone resorption and serum biomarkers of bone formation, bone resorption and inflammation
also will be assessed. In addition, another objective is to determine if the microbial
effects obtained with LDD over two years are equivalent to a placebo control. This clinical
trial involves two clinical sites: the University of Nebraska Medical Center College of
Dentistry and Stony Brook University School of Dental Medicine. A total of 128
postmenopausal osteopenic women with periodontitis between the ages of 45 and 70 at the time
of telephone screening will be randomized to LDD or placebo groups and subjects will be
followed for two years.

Inclusion Criteria:

- Subjects will be female, postmenopausal and not receiving estrogen replacement
therapy.

- Subjects will be 45-70 years old at the time of telephone screening.

- Subjects will have osteopenia (T-score of -1.0 to -2.5) of the lumbar spine or
femoral neck as determined by dual-energy absorptiometry (DEXA) scans.

- Subjects will have a history of generalized moderate-advanced periodontitis and will
be undergoing periodontal maintenance.

- Subjects will be in good general health and willing to sign the IRB-approved consent
form.

Exclusion Criteria:

- Subjects will not have an allergy or hypersensitivity to tetracyclines.

- Subjects will not have diseases or take medications that affect the inflammatory or
immune responses (e.g., chronic use of non-steroidal anti-inflammatory drugs) or bone
remodeling (e.g., drugs such as prescription estrogens, bisphosphonates, calcitonin
or steroids).

- Subjects will not have any medical condition requiring antibiotic premedication
(e.g., prosthetic heart valves, prosthetic joints, and mitral valve prolapse with
regurgitation) for routine dental therapy.

- Subjects cannot have diabetes mellitus.

- Subjects cannot have had active periodontal therapy (quadrant scaling and root
planing or periodontal surgery) within the past year.

- Subjects cannot have osteoporosis (T-score greater than -2.5) of the lumbar spine or
femoral neck.