Supervisors info:
1. Πεπελάση Ευδοξία, Αναπληρώτρια Καθηγήτρια Περιοδοντολογίας Οδοντιατρικής Σχολής Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
2. Καρούσης Ιωάννης, Αναπληρωτής Καθηγήτης Περιοδοντολογίας Οδοντιατρικής Σχολής Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
3. Μπομπέτσης Γεώργιος, Επίκουρος Καθηγήτης Περιοδοντολογίας Οδοντιατρικής Σχολής Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
Summary:
Introduction: The use of bone grafts for the regeneration of osseous defects constitutes a widely spread technique nowadays in the field of dentistry and implantology. Despite the fact that autogenous bone graft remains the gold standard in every case when bone regeneration is the endpoint, the disadvantages that are intrinsically associated with its harvesting have significantly restricted its use in clinical practice. A large variety of bone replacement grafts are commercially available, each of them showing different behavior and properties. Within them, porous titanium granules constitute an alloplastic bone replacement grafting material and several preclinical and clinical studies have supported its efficacy both in the fields of dentistry and orthopedics. Despite the fact that several evidence exists on the effect of various bone grafts locally on the tissues when applied for the treatment of osseous defects, no evidence exists up to now on the systemic effects of the use of bone grafts.
Studies in the field of orthopedics have shown that during fracture healing serum levels of bone turnover markers possibly change. Those systemic changes may reflect the underlying procedures that take place at a histological level at the site of injury. Factors such as the type of injury, the treatment strategy applied and the outcome of healing are likely to affect the magnitude and the overall duration of these changes.
Osseous defects are a type of tissue damage whose healing mechanisms at the histological level differ significantly from those of fracture healing, due to the different mechanical conditions that prevail at the injury site during healing. No literature data exist on the possible effect of osseous defects healing on the serum levels of bone turnover markers.
Moreover, irrespective of the type of defect that is studied, no literature data exist on the effect of the use of bone grafts for the treatment of any type of osseous lesion on the serum levels of bone turnover markers.
Purpose: the first purpose of the present experimental study on rabbits subjected to experimental induction of osseous defects in the femur was to evaluate the serum levels of Bone Alkaline Phosphatase (BALP), N-Terminal-Mid-molecule fragment of Osteocalcin (N-MID-OC), N-Terminal Procollagen type I Propeptides (PINP), C-Terminal Crosslinked Telopeptides of Type I Collagen (CTX), Tartrate-Resistant Acid Phosphatase 5 beta (TRAP5b) during the healing period. The second purpose was the comparative evaluation of BALP, N-MID-OC, PINP, CTX-I and TRAP5b serum level changes over time as related to the treatment strategy that was followed in rabbits subjected to experimental induction of osseous defects in the femur which were treated with the application of porous titanium granules, autogenous bone graft or were left to heal without the use of bone graft.
Materials and methods: The material of the present study was blood samples collected from 45 New Zealand type rabbits that had been subjected to experimental induction of standardized osseous defects in the right femur and which were randomized in three different treatment groups:
1. Porous titanium granules (PTG) and resorbable collagen membrane (M) – PTGM group
2. Autogenous bone graft (AG) and resorbable collagen membrane (M) – AGM group
3. Resorbable collagen membrane (M) – CM group
Blood samples had been collected from each animal prior to the initiation of the surgical procedure and 1, 2, 4 and 6(final) weeks postoperatively.
The quantitative evaluation of bone turnover markers serum levels was carried out by ELISA method (Enzyme-linked immunosorbent assay).
The results were analyzed through regression analysis models for repeated measurements. The correlations between the values of the various markers per group and measurement week were calculated with the Pearson correlation coefficient (r).
Results: Healing of osseous defects without the use of bone grafts resulted in statistically significant changes of CTX-I and TRAP5b levels. Moreover, some changes in the BALP and TRAP5b serum levels only marginally failed to reach statistical significance.
CTX-I, PINP and TRAP5b levels followed a similar pattern during the six week healing period in all three groups. BALP and N-MID-OC level followed a different pattern among the three groups, although N-MID-OC levels followed a similar pattern in groups PTGM and AGM after the second week of healing.
The final levels of all bone turnover markers were similar to baseline values for all groups and did not statistically significantly differ among groups. BALP, N-MID-OSC, PINP and TRAP5b level changes over time did not statistically significantly differ among groups. CTX level changes statistically significantly differed between PTGM group and the other two groups. CTX levels followed a similar pattern for all groups during these time intervals. Some differences of N-MID-OC and PINP level serum level changes over time among the three groups only marginally failed to reach statistical significance.
For PTGM group, there were significant positive correlations between N-MID-OC and PINP, N-MID-OC and TRAP5b as well as between PINP and TRAP5b. These correlations sustained for all time intervals showing high correlation coeffecients for several time periods. A similar correlation pattern was found for group AGM for all time intervals, except for the 4th week. The correlations were stronger for group PTGM than AGM for all time intervals.
Conclusions: Healing of experimentally induced osseous defects in the rabbit femur led to statistically significant changes in the serum levels of CTX-I and PINP. Some changes in the levels of BALP and TRAP5b only marginally failed to reach statistical significance.
The use of porous titanium granules for the treatment of osseous defects led to statistically significantly different serum level changes of CTX-I when compared to the use of autogenous bone graft or healing without the use of bone graft. Some differences in the serum level changes of N-MID-OC and PINP only marginally failed to reach statistical significance.
A larger sample size might lead to safer conclusions on the effect of the use of various bone grafts for the treatment of osseous defects on serum levels of bone turnover markers during the healing of osseous defects.
Keywords:
Porous titanium granules, oseeous defects, bone turnover markers, osseous graft
