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The development of diagnostic testing has presented a significant challenge to periodontology. Science has extensively evaluated markers for diagnostics tests to determine active disease or markers for prognostic tests that can predict disease. Periodontal diagnostic procedures are essential to patient assessment and include: 12
However, many diagnostic tests have not been subjected to rigorous testing to evaluate if they are applicable to the five areas mentioned above.12
Gingival crevice fluid (GCF) is an exudate easily obtained from the periodontal pocket or sulcus, and consequently it is utilized in the majority of new diagnostic tests for periodontal disease. Although researchers have identified approximately 50 different constituents in GCF, many are not specific to alveolar bone destruction. Instead, they are indicative of soft-tissue inflammatory events.12
Microbial infection and an inflammatory response precede the destruction of alveolar bone. Examination of this destruction and the detection of connective tissue-derived molecules may provide for a more precise assessment of the breakdown of tissue, especially in light of the tremendous variability demonstrated in the host response of different individuals. Over the past decade, advances in bone cell biology have produced several new biochemical markers that measure the homeostasis of bone. As research has yielded increasing evidence of the relationship between osteoporosis and oral bone loss, scientists have pursued the development of superior biologic markers to predict and determine oral bone loss.12
Extracellular matrix molecules that are derived from the periodontium have been identified in gingival crevicular fluid (GCF). Polypeptide growth factors are one classification of extracellular matrix molecules that can function as molecular mediators of tissue and bone repair. Their role is now recognized in bone homeostasis and release during acute and chronic inflammation. Polypeptide growth factors comprise a class of natural biological mediators. By binding to specific cell-surface receptors, they are able to regulate significant cellular events in tissue repair, including cell proliferation, chemotaxis, differentiation, and matrix synthesis.12
Various growth factors are found in concentrated amounts in the organic matrix of bone. Since these growth factors are released during bone resorption, it has been proposed that they may play a role in bone remodeling by regulating the coupling process of bone formation and resorption.12
Although researchers are actively studying the role played by various growth factors in the regeneration of periodontal tissue, they have yet to thoroughly investigate their prospective value as diagnostic markers of periodontal tissue inflammation and/or destruction. Various studies in the periodontal literature have reported the evaluation of gingival crevicular fluid and salivary levels of growth factors for their potential to diagnose periodontal disease, including epidermal growth factor (EGF), transforming growth factor- (TGF- ) and TGF- , platelet-derived growth factor (PDGF), and vascular-endothelial growth factor (VEGF).12
In 1999, the gingival crevicular fluid concentrations of epidermal growth factor and transforming growth factor- were compared in periodontal patients and healthy control subjects.12 No significant differences were noted in epidermal growth factor concentrations in the gingival crevicular fluid of the periodontal disease group and control groups. However, significantly lower concentrations of transforming growth factor- were present in the gingival crevicular fluid of patients with severe periodontal disease. In addition, there were significant correlations between the concentrations of transforming growth factor- in gingival crevicular fluid and pocket depth measurements, bleeding on probing, and radiographic bone loss.12
The relationship of these correlations remains unclear. However, the researchers theorized that since transforming growth factor- is associated with the wound healing process, the absence of this factor may lead to a delay in periodontal regeneration during progression of the disease. In addition, previous studies demonstrated significant differences in the concentrations of epidermal growth factor in gingival crevicular fluid recovered from deep versus shallow sites in periodontal patients and during orthodontic tooth movement.12
One study described lesser concentrations of epidermal growth factor in deep periodontal sites versus shallow sites, while another study reported greater concentrations of epidermal growth factor present in sites of active orthodontic tooth movement. When the total results are compared, they appear to be ambivalent about the usefulness of epidermal growth factor and the related transforming growth factor- as indicators of alveolar bone loss.12
Investigators evaluated levels of transforming growth factor- and platelet-derived growth factor in gingival crevicular fluid around failing dental implants. Patients with failing implants demonstrated higher levels of platelet-derived growth factor in gingival crevicular fluid at both failing and stable implant sites compared to control patients with stable implants. No sites in this study were found to have clinically detectable levels of transforming growth factor- .12
In a different study, deeper periodontal pockets demonstrated higher levels of transforming growth factor- in gingival crevicular fluid than less involved sites in periodontal patients. In addition, the investigators reported higher levels of transforming growth factor- in gingival crevicular fluid in beagle dogs with experimentally induced periodontitis. Although, the higher levels of transforming growth factor- were found only in sites with moderate disease progression, and the levels declined in sites with experimentally induced advanced periodontitis. These results further substantiate the proposed role played by transforming growth factor- in the reparative process.12
In 1998, vascular endothelial growth factor from the gingival crevicular fluid of a cross-section of periodontal patients and healthy control subjects was measured. Vascular endothelial growth factor occurred at higher levels in diseased sites and lower levels in healthy sites. While the role of vascular endothelial growth factor is accepted in the regulation of angiogenesis, the results of a study published in 2000 proposed that vascular endothelial growth factor may also play a significant role in regulating bone remodeling by stimulating osteoblast differentiation and by attracting endothelial cells and osteoclasts.12
Higher concentrations of vascular endothelial growth factor were also reported in diseased gingiva adjacent to 4-6-mm pockets, a fact that supports its potential contribution to periodontal disease progression. The investigators theorized that vascular endothelial growth factor may be significant in the progression of gingivitis to periodontitis because it promotes expansion of the vascular network that is present in inflammation.12
In spite of all the evidence from studies confirming the presence of different growth factors in gingival crevicular fluid, they have been unable to define any obvious tendency toward predicting the severity or activity of periodontal disease. A greater understanding of the role that these biological mediators play in the processes of periodontal tissue destruction and repair may facilitate a more clear demonstration of their potential value as periodontal diagnostic aids.12
Future research goals include the development of methodology enabling researchers to utilize expanded longitudinal clinical trial testing which will be critical in establishing whether or not a marker can predict oral bone loss. Increased sensitivity of bone-specific biomarkers in gingival crevicular fluid is also needed to provide accurate, predictable diagnoses to better serve our periodontal patients. Greater clarification of biomarkers of active periodontitis may help to explain the molecular mechanisms of the progression of periodontal diseases and give ‘real-time’ measures of bone metabolism.12