Immunopathogenetic mechanisms of periodontal disease and postmenopausal osteoporosis

Osteoporosis and periodontitis are widespread diseases among male and female population, whose incidence increases with aging. The basic pathogenic mechanism of osteoporosis and periodontal disease is a bone resorption with increased production of proinflammatory cytokines: interleukin IL-1β, IL-6, TNF-α and RANKL. The discovery of receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) has contributed to the understanding of bone biology and mechanisms of osteoclastogenesis. RANKL-RANK interaction is critical for differentiation and maintenance of osteoclast activity. The balance between RANKL and OPG regulates osteoclastogenesis, and thus bone resorption. The disruption of the RANKL/RANK/OPG axis leads to an imbalance between bone formation and bone resorption; therefore, it is responsible for the disturbed bone homeostasis. Loss of bone density associated with decreased estrogen levels is the result of a significant increase in osteoclast activity. Menopausal bone loss may be the result of osteoclast overactivation by proinflammatory cytokines and it is associated with reduced estrogen levels. The lack of estrogen can lead to worsening of periodontal disease and it increases the rate of the gingival connective tissue damage by stimulating the synthesis of several cytokines responsible for bone resorption. Cytokines and RANKL/OPG signaling pathway involved in the pathogenesis of osteoporosis and periodontal disease can lead to the activation of osteoclasts and the stimulation of bone resorption. These findings in the future may improve the usual treatment of periodontal disease and osteoporosis therapy, including the inhibition of proinflammatory mediators and osteoclast activity with the additional use of anti-inflammatory drugs. This involves blocking the binding of different stimulating factors to their receptors on osteoclast precursors, particularly RANKL and development of new more selective drugs with fewer side effects that would act as an anti-cytokines preventing the binding of cytokines to their receptors. Acta Medica Medianae 2012;51(4):51-57.