Host Modulatory Therapy

Oral microbiology research consistently demonstrates that beneficial microflora can transform into opportunistic pathogenic flora if their environment changes significantly. The hosts themselves affect the bacteria; the changes are not caused by the bacteria, but by the hosts. As human society grew more industrialized, the bacteria in human mouths became more pathogenic, or likely to lead to disease. The diversity of the oral microbiome has reduced significantly, and tooth decay has become a serious problem in developed countries. This is particularly problematic when viewed in contrast to pre-Neolithic people, who had very few incidences of dental cavities or gum disease, and it indicates the likelihood that changes in the host -- humans -- have had a deleterious effect on the oral microbiome.

With this in mind, scientists are currently exploring the options provided by host modulatory therapy, a periodontitis treatment that aims to modify the host response with the goal of stabilizing and sometimes even regenerating the periodontium while also reducing tissue destruction. Traditionally, treatments for periodontitis have aimed toward reducing the bacterial load in the oral cavity, though these treatments, by their very nature, have unpredictable results. Effective treatment of periodontitis must be two-pronged, simultaneously attempting to resolve inflammation and reduce destruction while also addressing the persistence and recurrence of bacterial buildup and destructive events. Ideally, reducing the destructive processes present in the oral cavity will enhance the stability of the periodontium following periodontal therapy. Host modulatory therapy aims to address the host, rather than the bacteria, toward the goal of stabilizing the effects of periodontal therapy.

There are several possible agents currently being used for host modulatory therapy. Non-steroidal anti-inflammatory drugs inhibit the formation of prostaglandin that is produced by the cells in the periodontium in response to bacteria. This prostaglandin upregulates the resorption of bone, and it is found in higher levels in patients who have periodontal disease. Reducing its levels can thereby lead to a reduction in bone resorption and a lessening of the effects of periodontitis. Bisphosphonates, which are drugs that prevent the depletion of bone density and are commonly used to treat osteoporosis, have been found to have similarly beneficial effects on bone resorption. Small doses of doxycycline are ineffective as antimicrobial treatment but have been found to inhibit the cellular functions that contribute to bone resorption. A 20 mg dose of doxycycline is sub-antimicrobial; when administered twice a day as an adjunct to the periodontal treatment of scaling and root planing, it has been shown to be effective at cellular inhibition. Enamel matrix proteins can help wounds heal and also stimulate the growth of lost bone, ligaments, and cementum, leading to a restoration of the entirety of the periodontal attachment apparatus. These proteins are extracted from the tooth material of fetal pigs, and they biomimetically stimulate the tissues to encourage regeneration following the destruction of tissues in the periodontium. Emdogain is the only currently approved enamel matrix protein used in dentistry. Growth factors and bone morphogenic proteins function similarly, encouraging and stimulating the regeneration of cells following their destruction.