Alveolar Bone Loss: Mechanisms, Potential Therapeutic Targets, and Interventions

This article reviews recent research into mechanisms underlying bone resorption andhighlights avenues of investigation that may generate new therapies to combat alveolarbone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietarysupplements are discussed as they relate to peri-odontal bone loss and regeneration. RGS12is a crucial protein that mediates osteoclastogenesis and bone destruction, and apotential therapeutic target. RGS12 likely regulates osteoclast differentiation throughregulating calcium influx to control the calcium oscillation-NFATc1 pathway. A workingmodel for RGS10 and RGS12 in the regulation of Ca2+ oscillations during osteoclastdifferentiation is proposed. Initiation of inflammation depends on host cell-microbeinteractions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway.Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a ratperiodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is amore specific therapeutic target with potentially superior tolerability. Furthermore,MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis andbone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bonemarrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derivedSSCs have shown therapeutic potential in several applications, including bone andperiodontal regeneration. The existence of craniofacial bone-specific SSCs is suggestedbased on existing studies. The effects of calcium, vitamin D, and soy isoflavonesupplementation on alveolar and skeletal bone loss in post-menopausal women wereinvestigated. Supplementation resulted in stabilization of forearm bone mass density and areduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontalattachment levels were also well-maintained and alveolar bone loss suppressed during 24 wkof supplementation.