Doxycycline effects on serum bone biomarkers in post-menopausal women

Abstract

We previously demonstrated that subantimicrobial-dose-doxycycline (SDD) treatment of post-menopausal osteopenic women significantly reduced periodontal disease progression, and biomarkers of collagen destruction and bone resorption locally in periodontal pockets, in a double-blind placebo-controlled clinical trial. We now hypothesize that SDD may also improve biomarkers of bone loss systemically in the same women, consistent with previous studies on tetracyclines (e.g., doxycycline) in organ culture and animal models of bone-deficiency disease. 128 post-menopausal osteopenic women with chronic periodontitis randomly received SDD or placebo tablets daily for 2 years adjunctive to periodontal maintenance therapy every 3-4 months. Blood was collected at baseline and at one- and two-year appointments, and sera were analyzed for bone resorption and bone formation/turnover biomarkers. In subsets of the study population, adjunctive SDD significantly reduced serum biomarkers of bone resorption (biomarkers of bone formation were unaffected), consistent with reduced risk of future systemic bone loss in these post-menopausal women not yet on anti-osteoporotic drugs.

Figure 1.

The effect of SDD relative to placebo on ICTP levels in serum in (A) subgroups of women within 5 yrs of menopause at baseline (no significant effect of SDD in women beyond 5 yrs of menopause, p = 0.8) and (B) women who did not receive significant concomitant medications (no significant SDD effect in women using significant concomitant medications, p = 0.5), where the baseline reference group represents all study participants, free of significant concomitant medication use (an eligibility criterion). Each bar represents the mean value, and whiskers are drawn to ± 1 standard error of the mean; subgroup sample size is shown below each bar value. SDD, subantimicrobial-dose doxycycline. ICTP, pyridinoline-crosslink degradation fragment of type I collagen.

Figure 2.

The effect of SDD relative to placebo on CTX levels in serum in (A) subgroups of women within 5 yrs of menopause (no significant SDD effect in women beyond 5 yrs of menopause, p = 0.4) and (B) women who did not receive significant concomitant medications (no significant SDD effect among women using significant concomitant medications, p = 0.8), where the baseline reference group represents all study participants, free of significant concomitant medication use (an eligibility criterion). Each bar represents the median value, and whiskers are drawn to the 25th and 75th percentiles; subgroup sample size is shown below each bar value. SDD, subantimicrobial-dose doxycycline. CTX, deoxypyridinoline-crosslink degradation fragments of type I collagen.