Clinical, radiographic and biochemical assessment of IL-1/TNF-alpha antagonist inhibition of bone loss in experimental periodontitis.
OBJECTIVE
To assess clinical, radiographic, and biochemical markers as diagnostic indicators of disease activity by comparing ligature-induced bone loss in the presence or absence of IL-1/TNF-alpha antagonist inhibition of bone loss in a primate model.


METHODS
6 animals with a naturally-occurring gingivitis were evaluated over a 6-week time period following the placement of silk ligatures and initiation of a soft diet. Three animals received intrapapillary injections of soluble receptors (blockers), capable of blocking the biologic activity for both IL-1 and TNF-alpha, and 3 animals received vehicle (control) injections. Injections were given 3X per week over the course of the study. Clinical assessments included a gingival index and quantification of gingival crevicular fluid (GCF) levels. Collected GCF samples were then used in the biochemical assessment of pyridinoline (PYD) and bone alkaline phosphatase (BAP). Radiographic assessment was made using computer-assisted subtraction radiography to measure both bone density (CADIA) values and linear changes in crestal bone height.


RESULTS
Significant (p<0.01) changes using both radiographic measures occurred between 2 and 4 weeks following initiation of disease in this model. The use of the blockers significantly (p<0.01) reduced the levels of radiographic bone loss by approximately 50% over that found in the control sites. Both biochemical markers showed the greatest increase during the first two weeks of the study with PYD levels increased 35-fold over baseline levels after 1 week. This difference in response was significantly (p<0.05) greater than the levels found in the non-ligated teeth or in the ligated teeth receiving blockers injections. BAP levels showed significant increases in ligated teeth compared to non-ligated teeth, but failed to show any significant differences between animals treated with vehicle and those treated with IL-1/TNF antagonists. In contrast to these radiographic and biochemical effects, there were no significant differences detected between animals treated with antagonists and the control group for any of the clinical measures.


CONCLUSIONS
The results of this study demonstrate that both subtraction radiography and PYD crevicular fluid levels can detect relative differences in periodontal disease progression, while BAP crevicular fluid levels cannot.
Oates
T W
TW
Department of Periodontics, University of Texas Health Science Center at San Antonio, TX 78229, USA. Oates@uthscsa.edu
Graves
D T
DT
Cochran
D L
DL
D000469:Alkaline Phosphatase / Q000032:analysis; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D000596:Amino Acids / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D004195:Disease Models, Animal; D018450:Disease Progression; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D005891:Gingivitis / Q000382:microbiology; D007091:Image Processing, Computer-Assisted; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008252:Macaca fascicularis; D010512:Periodontal Index; D010518:Periodontitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D014677:Pharmaceutical Vehicles; D016966:Porphyromonas gingivalis / Q000502:physiology; D011859:Radiography; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013382:Subtraction Technique; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000596:Amino Acids; D015415:Biomarkers; D007375:Interleukin-1; D014677:Pharmaceutical Vehicles; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C015484:pyridinoline; D000469:Alkaline Phosphatase