Table 3.
Pharmacological agents with potential host-modulation action
| Agent | Mechanism of action | Periodontal-related effects | References |
|---|---|---|---|
| NSAIDs | Inhibition of cyclooxygenase enzymes that participate in arachidonic acid metabolism Reduction of prostanoid production, specially prostaglandin E2 |
Significant reduction of alveolar bone loss Inconsistent benefits on clinical attachment gain or probing depth reduction |
(14, 20, 26, 84, 124, 146, 183, 184) |
| Bisphosphonates | Inhibition of osteoclast function | Significant attachment gain and probing depth reduction Significant alveolar bone gain |
(41, 96, 147, 151) |
| NO synthase inhibitors | Reduction of nitric oxide production through inhibition of NO synthases | Preclinical studies in rats Significant reduction of bone loss and gingival inflammation |
(101, 105) |
| rhIL-11 | Inhibition of pro-inflammatory cytokines and other mediators Stimulation of TIMP-1 |
Preclinical study in dogs Significant reduction of tissue attachment and bone loss |
(108, 172) |
| Omega-3 fatty acid | Inhibition of cyclooxygenase and lipooxygenase (arachidonic acid cascade) Reduction of prostanoids and leukotrienes, especially leukotriene B4 |
Preclinical study in rats Insignificant reduction of bone loss |
(177) |
| p38 MAPK inhibitors | Inhibit lipopolysaccharide-induced MMP, cytokine (IL-1β, TNF-α, IL-6, IL-8), and prostaglandin expression | Preclinical study in rats Significant reduction in bone loss |
(90) |
| JNK inhibitors | Inhibits TNF-α, IFN-γ, IL-6, COX-2, and MMP expression | None published to date | |
| NF-κB family inhibitors | Inhibits NF-κB-dependent expression (IL-1, TNF-α, IL-6, IL-8), MMPs, IFN-γ, others | None published to date | |
| TNF antagonists | Inhibits TNF-α | Preclinical primate studies Significant reduction of attachment loss and bone loss |
(8, 29, 30, 58) |
| RANKL/RANK/osteoprotegerin disruption therapeutics | Inhibits RANKL/RANK-mediated osteoclastogenesis | Preclinical studies in mice Significant reduction in alveolar bone loss |
(107, 171) |
COX-2, cyclooxygenase 2; JNK, c-jun N-terminal kinase; IFN-γ, interferon-γ; IL, interleukin; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; NO, nitric oxide; NSAID, non-steroidal anti-inflammatory drug; NF-κB, nuclear factor-kappa B; rh, recombinant human; TNF-α, tumor necrosis factor-α; RANK, receptor activator of NF-κB; RANKL, receptor activator of NF-κB ligand.