| Methods |
Type of study: placebo‐controlled, double‐blinded parallel RCT Stratification: the randomisation was stratified by study centre (University of Nebraska Medical Center College of Dentistry (UNMC COD) or Stony Brook) and current smoking status (current smoker or not current smoker) Sample size calculation: reported Funding: NIDCR grant Country: USA Timeframe of the study: June 2012 to October 2005 |
| Participants |
Centres: 2, UNMC COD and the School of Dental Medicine at Stony Brook University (Stony Brook) Inclusion criteria: 45‐70 years of age at telephone screening; postmenopausal for at least 6 months and not receiving hormone replacement therapy (HRT); osteopenia of the lumber spine or femoral neck (T‐score of ‐1.0 to ‐2.5 inclusive); history of generalized moderate to advanced periodontitis and undergoing periodontal maintenance; and having at least 9 posterior teeth and at least 2 sites with probing depths ≥ 5 mm together with bleeding on probing, ≥ 5 mm clinical attachment level loss, and radiographic evidence of alveolar bone height loss, were undergoing periodontal maintenance therapy. Subjects had no history of myocardial infarction, angina, or stroke. Subjects also had to be willing to sign UNMC and Stony Brook Institutional Review Board‐approved consent forms and had to be in good general health without co‐morbidities that may interfere with adherence to the study protocol, planned follow‐up or endpoint measurement Exclusion criteria: allergy or hypersensitivity to tetracyclines; diseases or regular drug therapy that would affect the inflammatory or immune response (e.g., chronic use of nonsteroidal anti‐inflammatory drugs (NSAIDs)) or bone remodeling (e.g., prescription estrogens, bisphosphonates, calcitonin, and steroids); requirement for antibiotic premedication; diabetes; active periodontal therapy within the past year; normal bone mineral density (BMD) at both the lumbar spine and femoral neck (T‐score above ‐1.0) or osteoporosis of the lumbar spine or femoral neck (T‐score less than ‐2.5) Participants: postmenopausal patients with chronic periodontitis and osteopenia of the lumber spine or femoral neck Number of participants: total 113; intervention group 51; control group 62 Gender of participants: total male 0, female 113; intervention group 51/0; control group: 62/0 Age of participants: total mean = 58.31; intervention group: 58.62±5.96 (SD); control group 58.06±5.73 Lost to follow‐up: the protocol was amended in April 2004, at which point 13 subjects had withdrawn consent (placebo n = 2, SDD n = 10) or had withdrawn (SDD n = 1) due to a serious adverse event, to allow measurement of inflammatory biomarkers in stored (‐80°C) serum. 2 additional SDD subjects withdrew following the protocol amendment and refused to complete an exit exam that included the addendum study consent request. 53 subjects were randomised at Stony Brook; 46 Stony Brook subjects completed the trial and signed an addendum consent form to conduct additional serum analyses (ApoA‐I and ApoA‐II assessment) and serum was not collected from 1 subject at the 1 year visit |
| Interventions |
Intervention group: 20 mg doxycycline twice daily for 2 years (low‐dose or subantimicrobial dose doxycycline; SDD) Control group: a placebo look‐alike twice daily for 2 years All subjects received calcium and vitamin D supplements twice daily (a total of 1200 mg of calcium and 400 IU of vitamin D daily). Subjects were instructed not to take the study drug and calcium/vitamin D at the same time, being certain the supplements were taken at least 1 hour after taking the study drug. All subjects received periodontal maintenance every 3‐4 months throughout the study, delivered by the subjects' own dental care providers and not by the study clinicians Duration of follow‐up: 24 months |
| Outcomes |
Serum hs‐CRP (measured by ELISA‐based assay, at baseline, 1 year and 2 years) Total cholesterol, HDL‐C and triglycerides (measured by ELISA‐based assay, measured at baseline, 1 year and 2 years) LDL, VLDL (measured by calculation, at baseline, 1 year and 2 years) Serum ApoA‐I and ApoA‐II (measured by ELISA‐based assay, at baseline, 1 year and 2 years) (Only the data from Stony Brook subjects were included because insufficient amounts of serum remained from the Nebraska subjects after completion of the biomarker analyses) |
| Notes |
All the included participants were female and had osteopenia of the lumber spine or femoral neck. The eligibility is not clear. Some data need confirmation from the authors and the eligibility needs further discussion |
