Using tetracyclines to treat osteoporotic/osteopenic bone loss: from the basic science laboratory to the clinic

Periodontitis (progressive inflammatory disease characterized by alveolar bone loss, a major cause of tooth loss worldwide) is associated with both systemic osteoporosis and its milder form, osteopenia. Tetracyclines, by virtue of their non-antimicrobial pro-anabolic and anti-catabolic properties, are excellent candidate pharmaceuticals to simultaneously treat these local and systemic disorders. This paper reviews the foundational basic science and translational research which lead to a pivotal multicenter randomized clinical trial in postmenopausal women with both periodontitis and systemic (skeletal) osteopenia. This trial was designed primarily to examine whether subantimicrobial dose doxycycline (SDD) could reduce progressive alveolar (oral) bone loss associated with periodontitis and, secondarily, whether SDD could reduce systemic bone loss in the same subjects. This paper describes the efficacy and safety findings from this clinical trial and also outlines future directions using this promising and novel approach to manage both oral and systemic bone loss.