Small molecule stimulation enhances bone regeneration but not titanium implant osseointegration.

The osteogenic and osseointegrative potential of a small molecule was examined to assess its usefulness in regenerative procedures. Purmorphamine was used to stimulate bone growth and repair in an in vitro cell-based assay and an in vivo chick embryo CAM-assay with and without the presence of an implant. Purmorphamine adhered to precipitated hydroxyapatite coating, could activate the sonic hedgehog pathway and thereby stimulated osteodifferentiation. Porous calcium phosphate beads were used to deliver this small molecule in vivo and showed that purmorphamine increased the trabecular bone to bone area significantly. The assay showed purmorphamine failed to induce any significant difference in osseointegration on titanium coated PTFE implants. This suggests that, while a small molecule can enhance osteogenesis and might be useful in regenerative procedures, it failed to enhance the osseointegration of a Ti coated implant, suggesting that this sort of stimulation might be useful for enhancing bone regeneration where bone loss due to disease exists, but not for enhancing early stability of an implant.

Relative contribution of patient-, tooth-, and site-associated variability on the clinical outcomes of subgingival debridement. I. Probing depths.

BACKGROUND: The objective of this clinical trial was to assess the relative contribution of patient-, tooth-, and site-associated variables on changes in probing depths (PD) following delivery of a standard non-surgical phase of periodontal therapy. METHODS: Ninety-four (94) systemically healthy subjects with severe generalized periodontitis were included in this 6-month prospective longitudinal study. Medical, periodontal, and microbiological parameters were collected at baseline and 2 and 6 months after completion of oral hygiene instructions, motivation, and subgingival debridement using a piezoelectric instrument. The relative contribution of patient-, tooth-, and site-associated variables was evaluated with a hierarchical multilevel analysis. RESULTS: Eighty percent (80%) of variability in PD reductions was attributed to site level parameters, while 12% was at the tooth level and 8% at the patient level. The multilevel analysis associated PD reductions with patient factors (cigarette smoking status and carriage of the rare allele of a specific polymorphism for the interleukin-6 [IL-6] gene), tooth factors (tooth mobility and tooth type), and site factors (mesial and distal location). Cigarette smoking and carriage of the rare allele of the IL- 6-174 G/C polymorphism were associated with less PD reduction. Incisors and canines responded better than premolars and molars. A dose-dependent effect of mobility was observed: teeth with higher baseline mobility resulted in significantly greater decreases in PD. At the site level, greater reductions were observed at interdental sites (compared to facial or oral), and at deeper sites (1.2 mm for 4 to 5 mm pockets and 2.4 mm for pockets > or =6 mm). CONCLUSION: These data provided an estimation of the relative contribution of site-, tooth-, and patient-associated variables in terms of PD reductions following a standard course of machine-driven subgingival debridement.

Periodontitis and atherogenesis: causal association or simple coincidence?

OBJECTIVES: The aim of this study was to assess the systemic effects of treating severe widespread periodontitis in a population of otherwise healthy individuals by examining treatment associated changes in markers of inflammation that are also implicated in cardiovascular atherosclerotic diseases. The potential impact of specific polymorphisms in cytokine genes known to influence both periodontitis and cardiovascular diseases was also examined. MATERIALS AND METHODS: A convenience sample of patients affected with severe generalised periodontitis was enrolled into a prospective single blind longitudinal intervention trial with a 6 months follow-up. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assessed by high-sensitivity assays. Serological and clinical periodontal parameters were evaluated at baseline, 2 and 6 months after completion of non-surgical periodontal therapy. RESULTS: In the 94 subjects that completed this pilot trial improvements in all clinical periodontal parameters were achieved. These were accompanied with significant reductions in serum IL-6 and CRP concentrations. In a multivariate model, serum CRP levels were significantly associated with the outcome of periodontal treatment after correcting for potential covariates (age, body mass index, gender, smoking) and polymorphisms in the IL-6 (-174 C/G) and IL-1A (-889) genes. A median decrease in serum CRP of 0.5 mg/l (95% CI 0.4-0.7 mg/l) was observed 6 months after completion of periodontal therapy in this population. Subjects with above average response to periodontal therapy (<30 residual pockets and <30% of sites bleeding on probing) accounted for the observed improvement in serum CRP. CONCLUSIONS: Control of periodontitis, achieved with non-surgical periodontal therapy, significantly decreased serum mediators and markers of acute phase response. The significance of the serum response was associated with the half of the population that responded better to non-surgical periodontal therapy. The results of this pilot study indicate that severe generalised periodontitis causes systemic inflammation. This is consistent with a causative role of periodontitis in atherogenesis.