Subantimicrobial dose doxycycline effects on alveolar bone loss in post-menopausal women

Abstract

Aim: Determine the efficacy of 2-year continuous subantimicrobial dose doxycycline (SDD; 20 mg bid) on alveolar bone in post-menopausal osteopenic, oestrogen-deficient women undergoing periodontal maintenance in a 2-year double-blind, placebo-controlled, randomized clinical trial.

Material and methods: One-hundred and twenty-eight subjects randomized to SDD or placebo (n=64 each). Posterior vertical bite wings taken at baseline, 1 and 2 years for alveolar bone density (ABD), using radiographic absorptiometry (RA) and computer-assisted densitometric image analysis (CADIA), and alveolar bone height (ABH). Statistical analyses utilized generalized estimating equations; primary analyses were intent to treat (ITT). Results are presented as SDD versus placebo.

Results: Under ITT, there was no statistically significant effect of SDD on ABD loss (RA: p=0.8; CADIA: p=0.2) or ABH loss (p=0.2). Most sites (81-95%) were inactive. For subgroup analyses, mean CADIA was higher with SDD for non-smokers (p=0.05) and baseline probing depths > or =5 mm (p=0.003). SDD was associated with 29% lower odds of more progressive ABH loss in women >5 years post-menopausal (p=0.05) and 36% lower among protocol-adherent subjects (p=0.03).

Conclusions: In post-menopausal osteopenic women with periodontitis, SDD did not differ overall from placebo. Based on exploratory subgroup analyses, additional research is needed to determine the usefulness of SDD in non-smokers, subjects >5 years post-menopausal and in deeper pockets. Protocol registered at (ClinicalTrials.gov). Identifier: NCT00066027.

Figures

Figure 1

Patient recruitment and follow-up flowchart showing the flow of subjects through each stage of the clinical trial, from screening through completion of the study protocol and through statistical analyses (intent-to-treat). Sixty subjects satisfied the per-protocol criteria (28 placebo and 32 SDD subjects) at one year and 43 subjects satisfied the per-protocol criteria (19 placebo and 24 SDD subjects) at the two-year time point.

Figure 2

Percentage of sites demonstrating alveolar bone height changes over one and two years based on per-protocol analysis (subjects who adhered to the protocol). Threshold for change was ± 0.4 mm, based on two times the standard deviation of replicate measurements.

Figure 3

Percentage of sites demonstrating CADIA density changes over one and two years in non-smokers and smokers (subgroup analysis). For the placebo group, 49 non-smokers and 13 smokers were included in the analysis. For the SDD group, 44 non-smokers and 11 smokers were included in the analysis. Thresholds for a decrease or increase in alveolar bone density were ± 17 units for crestal CADIA change and ± 14 units for subcrestal CADIA change. These thresholds were based on two times the standard deviation of replicate measurements.

Figure 4

Mean CADIA density changes over one and two years in non-smokers and smokers (subgroup analysis). For the placebo group, 49 non-smokers and 13 smokers were included in the analysis. For the SDD group, 44 non-smokers and 11 smokers were included in the analysis. Differences in mean change are presented as SDD minus placebo.

Figure 5

Mean CADIA density changes over one and two years by posterior interproximal location (subgroup analysis). For the placebo and SDD groups, respectively, 62 and 55 subjects contributed site location subgroup data. Differences in mean change are presented as SDD minus placebo.

Figure 6

Mean CADIA density changes over one and two years based on baseline probing depth (1−4 mm and ≥ 5 mm; subgroup analysis). Differences in mean change are presented as SDD minus placebo. For the placebo group, 62 and 61 subjects were included in the analyses for 1−4 mm probing depths and ≥ 5 mm probing depths, respectively. For the SDD group, 55 subjects and 51 subjects were included in the analyses for 1−4 mm probing depths and ≥ 5 mm probing depths, respectively

Figure 7

Percentage of sites demonstrating alveolar bone height changes over one and two years based on number of years postmenopausal (≤ 5 years and > 5 years; subgroup analysis). For the placebo group, 22 and 40 subjects were included in the analyses for women ≤ 5 years postmenopausal and > 5 years postmenopausal, respectively, while for the SDD group, 22 and 33 subjects were included in the analyses for women ≤ 5 years postmenopausal and > 5 years postmenopausal, respectively. Threshold for change was ± 0.4 mm, based on two times the standard deviation of replicate measurements.