Subantimicrobial dose doxycycline effects on osteopenic bone loss: Microbiologic results

Background: Based on microbiologic concerns, the safety of a 24-month regimen of subantimicrobial dose doxycycline (SDD; 20 mg twice a day) was evaluated in postmenopausal osteopenic women with periodontitis in a double-blind, placebo-controlled, randomized clinical trial. Methods: Subgingival samples were collected from two sites (probing depth ≥5 mm) in each of 128 subjects at baseline, with the same sites resampled at the conclusion of the 2-year period. The samples were enumerated on selective and non-selective media and on doxycycline (4 μg/ml) medium. Up to five different colonial morphologies were subcultured from the doxycycline medium, identified to species, and susceptibilities determined to doxycycline and five other antibiotics. Data were analyzed for microbial differences in total colony forming units (CFU), periodontal and opportunistic pathogens, and changes in species and in susceptibilities of isolates recovered on doxycycline medium. Results: There was no significant evidence that changes in total anaerobic counts over the treatment period (P = 0.96) differed between treatment groups. Likewise, periodontal pathogens, opportunistic pathogens, or normal flora did not differ descriptively between groups. Although there was a significant increase (P <0.001) in the total CFU recovered from the 4 μg/ml doxycycline plates at 24 months for SDD versus placebo, the percentage that was clinically resistant to doxycycline (minimal inhibitory concentration [MIC] ≥16 μg/ml) decreased over the 24-month period in both groups and did not differ between the treatment groups (SDD: 79% to 76%; placebo: 83% to 70%; P = 0.2). There were no significant differences (P >0.28 for each) in the change in cross-resistance between the groups for doxycycline and the other five antibiotics. Conclusions: No antimicrobial effect on the subgingival flora was detected following treatment with SDD for 24 months, relative to baseline or to placebo. The increase in initial resistance (at 4 μg /ml) did not translate into a significant increase in the percent resistant to doxycycline (MIC ≥ 16 μg/ml) for patients in the SDD group.