Biomechanical and morphological changes produced by ionizing radiation on bone tissue surrounding dental implant

Abstract Objective: This study analyzed the effect of ionizing radiation on bone microarchitecture and biomechanical properties in the bone tissue surrounding a dental implant. Methodology: Twenty rabbits received three dental morse taper junction implants: one in the left tibia and two in the right tibia. The animals were randomized into two groups: the nonirradiated group (control group) and the irradiated group, which received 30 Gy in a single dose 2 weeks after the implant procedure. Four weeks after the implant procedure, the animals were sacrificed, and the implant/bone specimens were used for each experiment. The specimens (n=10) of the right tibia were examined by microcomputed tomography to measure the cortical volume (CtV, mm3), cortical thickness (CtTh, mm) and porosity (CtPo, %). The other specimens (n=10) were examined by dynamic indentation to measure the elastic modulus (E, GPa) and Vickers hardness (VHN, N/mm2) in the bone. The specimens of the left tibia (n=10) were subjected to pull-out tests to calculate the failure load (N), displacement (mm) up to the failure point and interface stiffness (N/mm). In the irradiated group, two measurements were performed: close, at 1 mm surrounding the implant surface, and distant, at 2.5 mm from the external limit of the first measurement. Data were analyzed using one-way ANOVA, Tukey’s test and Student’s t-test (α=0.05). Results: The irradiated bone closer to the implant surface had lower elastic modulus (E), Vickers hardness (VHN), Ct.Th, and Ct.V values and a higher Ct.Po value than the bone distant to the implant (P<0.04). The irradiated bone that was distant from the implant surface had lower E, VHN, and Ct.Th values and a higher Ct.Po value than the nonirradiated bone (P<0.04). The nonirradiated bone had higher failure loads, displacements and stiffness values than the irradiated bone (P<0.02). Conclusion: Ionizing radiation in dental implants resulted in negative effects on the microarchitecture and biomechanical properties of bone tissue, mainly near the surface of the implant.


Introduction
The life expectancy of the world population has increased, and consequently, the need for dental implants as part of oral rehabilitation did as well. 1,2 The incidence of head and neck cancer has also increased, and radiotherapy may be indicated for patients with previously installed dental implants. Thus, clinicians are faced with the question of whether to remove or maintain osseointegrated implants before radiotherapy for head and neck cancer treatment. Several studies have been performed to evaluate implant survival in previously irradiated areas. [2][3][4][5] However, few studies have evaluated the presence of osseointegrated implants in irradiated bone areas. 1,4,6,7 The presence of titanium implants in irradiated areas can create a deleterious effect on bone tissue.
Backscatter high-energy photons and electrons at the tissue-metal interface may also compromise bone repair. 5,[8][9][10] In addition, ionizing radiation induces persistent hypoxia in small blood vessels and decreases the activity and quantity of osteoblasts and osteocytes, 2,5,10 which can increase the occurrence of osteoradionecrosis. 5,9 These effects have hindered efforts to determine the best moment to install implants after irradiation. 2,4 During head and neck tumour ablative surgery, dental implants can be installed in areas that need to be treated using radiotherapy. 1,4,6,7 The stability of titanium implants in the osseointegration process is compromised by radiation in a dose-dependent manner. 11,12 Additionally, there is no consensus regarding the impact of ionizing irradiation on the functionality or survival of the implant installed in the irradiation field. Notably, the effect of ionizing radiation is dose dependent. 11,12 A single dose of 30 Gy has been demonstrated to be sufficient to cause a negative influence on bone/implant integrity in a rabbit study model. 11,12 Radiotherapy is one of the most common treatments for head and neck cancer patients, 4,13 and ionizing radiation can reduce bone healing capacity through the progressive fibrosis of blood vessels and soft tissue, 14 loss of osteoblast function 15 and damage to the collagen arrangement. 16 These effects can also negatively influence bone/implant integration. 5,10 Studies have been carried out to evaluate implant survival in previously irradiated areas, 2,3,5 but there are limited data on the effect of backscattered radiation on the osseointegration process of implants placed before ionizing radiation. 1,4,5,7,8 Although backscattering effects around the implant can be a problem for individuals with implant rehabilitation, 1,4,10 the risk of radionecrosis is not significantly higher than that for postimplantation radiotherapy. 1,4,10 Therefore, the aim of this study was to evaluate the effects of ionizing radiation on the rabbit bone surrounding an implant using microcomputed tomography (micro-CT) and biomechanical analysis.

Methodology
The present preclinical in vivo study is reported Twenty New Zealand white male rabbits that weighed between 3.0 and 3.5 kg and were 6 months of age were included in the study. All animals were acclimatized for 2 weeks before the experimental procedures. The overlying soft tissues were removed, and the tibia were stored in plastic tubes containing phosphatebuffered saline solution and frozen at -20°C before testing. The implant installed in the left tibia was used for the pull-out test, one implant installed in the right

Dynamic indentation test
The elastic modulus (E, GPa) and Vickers hardness

Micro-CT analysis -bone microarchitecture
The micro-CT results are shown in Table 1

Dynamic indentation test -E and VHN
The dynamic indentation test results are shown in Table 2. The bone tissue of the nonirradiated group

Pull-out test -implant/bone structure stability
The pull-out test results are shown in Table 3. The

Discussion
The results of this study showed that ionizing radiation decreases bone mass, compromising the biomechanical properties of bone around dental

Groups
Ct.V (mm 3    Moreover, apoptosis is induced in osteoblasts exposed to irradiation, as they have higher radiosensitivity than other bone cells. 27 Three-dimensional micro-CT analysis was used as this modality is recommended to quantify the bone matrix and to present results that are similar to those found in histomorphometric analyses. 28 In addition, this study used biomechanical    This study has the same limitations as other studies, including that there was no load on the implants and that the implants were installed only in cortical bone.
Most likely, the fatigue process of the loading process may intensify this influence. The use of a single dose of ionizing radiation in an animal research model can also be considered a limitation as the healing process can be intensified when the dose is fractionated by a systemic response. The results of this study cannot be directly extrapolated to clinical practice, but our findings may indicate a possible correlation with the irradiation response observed in humans. 15 In patients with head and neck cancer that need to undergo radiotherapy, the observation of previously installed implants should be an important consideration. 7,8 Given the lack of protocols that aim to address such situations, the irradiation field should be limited as much as possible to avoid implant areas, and patients need to return frequently to the dental office to analyse implant stability.

Conclusion
Within the limitations of this in vitro study that tested the ionizing radiation over the pre-installed implants, the following conclusions can be drawn: Irradiation decreased the failure load and displacement of implant when tested by pull-out test.
Irradiation decreased the mechanical properties,