Bone-Turnover Markers in Postmenopausal-Osteopenic Women with Periodontitis (POWP): Subantimicrobial-Dose-Doxycycline (SDD)

We previously demonstrated, in a double-blind placebo-controlled trial on POWP, that 2-year SDD treatment (SDD-Tx) REDUCED severity of periodontitis and gingival crevicular fluid collagenase and bone collagen degradation fragments (ICTP). Objectives: To determine whether biomarkers of SYSTEMIC bone-turnover in these POWP were similarly improved by SDD-Tx adjunctive to periodontal maintenance therapy (PMT). Methods: 128 POWP were randomized to SDD (n=64) or placebo (n=64). Both groups also received daily calcium and vitamin D and PMT every 3-4 months for 2 years. Blood was collected at baseline, 1- & 2- year appointments and sera analyzed for ICTP by RIA and for CTx, bone-specific alkaline phosphatase (alk. phos.) and osteocalcin by ELISA. Statistical analyses were performed using Generalized Estimating Equations; primary analyses were intent-to-treat (ITT). Per-protocol and sub-group analyses also were conducted. Results: Based on ITT, SDD did not produce significant changes (p≥0.1) in serum biomarkers of bone resorption (ICTP; CTx) and bone formation & turnover (alk. phos.; osteocalcin). However, in subsets of these POWP, SDD-Tx significantly reduced mean serum ICTP levels (p=0.0003) compared to placebo in women postmenopausal for 5 years or less and in subjects not on significant concomitant medications (p=0.05). Median CTx levels showed a reduction similar to ICTP due to SDD-Tx in these subgroups which was marginally significant (p=0.06 for each); moreover, these bone resorption biomarkers were positively correlated at all time periods (p≤0.006). In contrast, SDD had no clear effect on markers of bone formation. Conclusions: In overall ITT analysis, SDD did not differ from placebo. However, in subgroups, SDD significantly reduced biomarkers of systemic bone resorption, with no detectable effects on bone formation, in subjects who were 5 years or less postmenopausal, and who did not receive significant concomitant medications. Supported by grants from NIDCR/NIH (R01DE012872) and from Academy of Finland & Helsinki U. Central Hospital.