To Örebro University

Purpose: Irradiation results in deleterious effects on bone healing and integration of titanium implants. The impact of irradiation on osseointegration has been demonstrated in histologic studies, but the underlying molecular mechanisms have not been explored. This study aimed to investigate the effects of single-dose irradiation on the expression of biologic mediators crucial for inflammation, bone formation, and bone remodeling and to relate these molecular activities to implant stability after a 5-week healing period.

Materials and Methods: A rat tibia model was used. An external single-dose irradiation of 20 Gy was administered to one leg while the second leg was used as a control. After 8 weeks, the irradiated and non-irradiated tibiae received titanium implants. Five weeks following implantation, implant stability was evaluated by removal torque measurement. Then, the implant and the bone surrounding the implant were retrieved for gene expression analysis of the implant-adherent cells and peri-implant bone, respectively.

Results: Irradiation resulted in 55% reduction in removal torque. The implant-adherent cells in irradiated sites revealed downregulation of genes related to bone formation (ALP and OC) and upregulation of pro-inflammatory (TNF-alpha) and pro-fibrogenic (PDGF-b) genes. Conversely, the peri-implant bone in irradiated sites revealed upregulation of bone formation and bone remodeling genes. Removal torque showed a negative correlation with pro-inflammatory activity and a positive correlation with osteoblastic activity in the implant-adherent cells.

Conclusion: The impact of high (20 Gy) single-dose irradiation on osseointegration involves a reduction in bone formation activity and upregulation of pro-inflammatory and pro-fibrogenic activities in the implant-adherent cells. It is also suggested that this single-dose irradiation elicits a different molecular pattern at a distance from the implant surface, characterized by increased bone formation and remodeling activities in the peri-implant bone.

Radiation has an impact on the processes involved in bone- healing, regeneration and remodeling. The mechanisms that cause impaired bone healing of dental implants are not fully understood. Adjunctive treatments to revers radiation effects are limited. Dental implant surgery can be a risk in irradiated jaws and the risk for osteoradionecrosis is of concern. There is no consensus when to install implant after completed radiation therapy or what radiation dosage might cause impaired bone healing. The overall aim of the studies was to investigate bone tissue reactions adjacent to implants after irradiation.

I. A clinically long-term follow-up study was performed to assess the outcome of 18 dental implants inserted in five patients with and without irradiated fibula-reconstructed mandibles. Bone tissue reactions adjacent to 14 micro-implants were histologically evaluated. In the clinical follow-up, 15 implants were in function, with an overall success rate of 83%. The histomorphometric analyses demonstrated an impaired osseointegration with reduced bone-to-implant contact (BIC) and bone area (BA), in irradiated sides.

II. In an experimental animal study the aim was to find a critical level for a given single external radiation dosages causing impaired implant osseointegration. 9 rats received a single radiation dose of 2, 5, 10, 20 and 30 Gy, respectively to one hind-leg while the other served as a control. Three days post radiation two implants were inserted in each hind-leg and after a period of 5 weeks the implants (n=36) were harvested for histological examination. BIC and BA were lower for irradiated samples for dosages of 20 Gy and higher.

III. The aim was to investigate the effects of HBO on osseointegration of titanium implants in irradiated bone. 15 rats received an external single radiation dose of 20 Gy to one hind-leg. 3-days post-irradiation 2 implants were inserted in each hind-leg (n=60). The rats were divided in to 2 groups and one group received hyperbaric oxygen treatment (HBOT) 3 days post-implant insertion (n=8). After 5 weeks the distal implants were harvested for histological examination (n=30) and the proximal implants were used for removal torque tests (n=30). BIC obtained significant higher values for non-irradiated side, independent of HBO or not. BA obtained significant higher values for irradiated sides in the non-HBO group.

IV. The aim was to investigate gene expression in irradiate bone after implant insertion for bone formation, resorption and remodelling. 8 rats, received a single radiation dose of 20 Gy to one hind-leg and two implants inserted in each hind-leg 8 weeks after completed radiation therapy. After 5 weeks bone samples with implants were collected for gene expression analysis. ALP, OC (formation) and RANKL/OPG (remodelling) were down regulated in irradiated samples.

Conclusion: Bone-anchored dental bridges can be used in selected oro-mandibular reconstructed patients. Bone quality disturbances with impaired osseointegration for dosages of 20 Gy and more were demonstrated in an animal study model. HBO did not enhance osseointegration of implants placed in rat bone during a five-week follow-up period. Irradiation significant reduces bone formation and remodeling under influence of pro-inflammatory and growth factor cytokines

Purpose: Hyperbaric oxygen (HBO) has been recommended to enhance implant osseointegration in irradiated bone. The aim of this study was to further investigate the effects of HBO on implant integration in irradiated bone tissue.

Materials and Methods: The present study was an experimental intraindividual study in 16 rats. A single fraction of 20 Gy external irradiation was applied to one rat hind leg, while the other served as a nonirradiated control. Three days after radiation, two implants were inserted in each tibial tuberosity. The rats were divided into two groups: non-HBO treated (group 1) and HBO treated (group 2). Five weeks after radiation, removal torque tests were performed. Implants with surrounding tissue were processed to undecalcified cut and ground sections for histomorphometric evaluations of bone-to-implant contact and bone area. Retrieved bones were also investigated with dual-energy x-ray absorptiometry.

Results: The non-HBO treated rats (group 1) demonstrated higher, but not statistically significantly higher, values in the nonirradiated leg for all investigated parameters compared to the HBO-treated rats (group 2). However, the mean value for bone area was significantly higher in the irradiated sides compared to the nonirradiated control sides.

Conclusions: In the present study, HBO treatment did not have a significant impact on osseointegration of implants in irradiated bone.

Aim: No general consensus exists regarding the ideal time to insert implants in bone after irradiation or how the various irradiation doses influence implant success. This study aims at investigating integration of implants in pre-irradiated rat bone and find a critical level doses that cause disturbed osseointegration.

Materials and methods: Single irradiation doses of 2, 5, 10, 20 and 30 Gy were given to one leg of adult rats 3 days prior to insertion of screw-shaped implants whereas the other leg served as a non-irradiated control. The follow up was 5 weeks. Bone implant contact (BIC) and bone area (BA) were measured on undecalcified cut and ground sections in the light microscope. The tissue quality was also examined in the light microscope.

Results: Doses of 5 and 10 Gy resulted in 25% higher contact values for the irradiated samples compared to non-irradiated controls. The most impaired integration occurred when doses of 20 Gy were given, revealing a 50% difference between the irradiated (25%) and the non irradiated samples (50%). The bone area demonstrated no major quantitative differences albeit the qualitative observations differed substantially being most pronounced in the 20 and 30 Gy irradiated samples.

Conclusions: The osseointegration was substantially impaired after radiation doses of 20 and 30 Gy. Quantitative data alone are insufficient to describe implant integration in situation like this. Qualitative observations are of utmost importance and require great attention. The importance of judging and describing various grades of tissue damage is complicated but necessary. Based on the results obtained in this study, full scale experiments are now ongoing.

På Käkkirurgiska kliniken vid Universitetssjukhuset i Örebro (USÖ) har vi inom den högspecialiserade vården utvecklat en flerårig och bred erfarenhet av framför allt käkrekonstruktioner och käkledskirurgi. Utöver den kirurgiska verksamheten är samarbete, både nationellt och internationellt, en viktig del av vår vardag.

Käkkirurgiska forskningsenhetens pågående projekt består till stor del av klinisk patientnära forskning, vilket är ett av Örebro universitets prioriterade forskningsområden.