Ex-vivo parametric study of laser ablation-based drilling of cortical bone.

Frequently orthopedic surgeries require mechanical drilling processes especially for inserted biodegradable screws or removing small bone lesions. However mechanical drilling techniques induce large number of forces as well as have substantially lower material removal rates resulting in prolong healing times. This study focuses on analyzing the impact of quasi-continuous laser drilling on the bone's surface as well as optimizing the drilling conditions to achieve high material removal rates. An ex-vivo study was conducted on the cortical region of desiccated bovine bone. The laser-based drilling on the bovine bine specimens was conducted in an argon atmosphere using a number of laser pulses ranging from 100 to 15,000. The morphology of the resulting laser drilled cavities was characterized using Energy dispersive Spectroscopy (EDS) and the width and depth of the drills were measured using a laser based Profilometer. Data from the profilometer was then used to calculate material removal rates. At last, the material removal rates and laser processing parameters were used to develop a statistical model based on Design of Experiments (DOE) approach to predict the optimal laser drilling parameters. The main outcome of the study based on the laser drilled cavities was that as the number of laser pulses increases, the depth and diameter of the cavities progressively increase. However, the material removal rates revealed a decrease in value at a point between 4000 and 6000 laser pulses. Therefore, based on the sequential sum of square method, a polynomial curve to the 6th power was fit to the experimental data. The predicted equation of the curve had a p-value of 0.0010 indicating statistical significance and predicted the maximum material removal rate to be 32.10 mm3/s with 95%CI [28.3,35.9] which was associated with the optimum number of laser pulses of 4820. Whereas the experimental verification of bone drilling with 4820 laser pulses yielded a material removal rate of 33.37 mm3/s. Therefore, this study found that the carbonized layer formed due to laser processing had a decreased carbon content and helped in increasing the material removal rate. Then using the experimental data, a polymetric equation to the sixth power was developed which predicted the optimized material removal rate to occur at 4820 pulses.

Effects of processing and gamma radiation on mechanical properties and organic composition of frozen, freeze-dried and demineralised human cortical bone allograft.

Bone processing and radiation were reported to influence mechanical properties of cortical bones due in part to structural changes and denaturation of collagen composition. This comparative study was to determine effects of bone processing on mechanical properties and organic composition, and to what extent the radiation damaging after each processing. Human femur cortical bones were processed by freezing, freeze-drying and demineralisation and then gamma irradiated at 5, 15, 20, 25 and 50 kGy. In the compression test, freeze drying significantly decreased the Young's Modulus by 15%, while demineralisation reduced further by 90% (P < 0.05) when compared to the freezing. Only demineralisation significantly reduced ultimate strength of bone by 93% (P < 0.05). In the bending test, both freeze drying and demineralisation significantly reduced the ultimate strength and the work to failure. Radiation at 25 kGy showed no effect on compression for ultimate strength in each processing group. However, high dose of 50 kGy significantly reduced bending ultimate strength by 47% in demineralisation group. Alterations in collagen in bones irradiated at 25 and 50 kGy showed by the highest peak of the amide I collagen in the Fourier Transfer Infra-Red spectra indicating more collagen was exposed after calcium was removed in the demineralised bone, however radiation showed no effect on the collagen crosslink. The study confirmed that demineralisation further reduced the ability to resist deformation in response to an applied force in freeze-dried bones due to calcium reduction and collagen composition. Sterilisation dose of 25 kGy has no effect on mechanical properties and collagen composition of the processed human cortical bone.

Deep-Freezing Temperatures During Irradiation Preserves the Compressive Strength of Human Cortical Bone Allografts: A Cadaver Study.

BACKGROUND: Gamma irradiation, which minimizes the risk of infectious disease transmission when human bone allograft is used, has been found to negatively affect its biomechanical properties. However, in those studies, the deep-freezing temperature during irradiation was not necessarily maintained during transportation and sterilization, which may have affected the findings. Prior reports have also suggested that controlled deep freezing may mitigate the detrimental effects of irradiation on the mechanical properties of bone allograft. QUESTION/PURPOSE: Does a controlled deep-freezing temperature during irradiation help preserve the compressive mechanical properties of human femoral cortical bone allografts? METHODS: Cortical bone cube samples, each measuring 64 mm3, were cut from the mid-diaphyseal midshaft of five fresh-frozen cadaver femurs (four male donors, mean [range] age at procurement 42 years [42 to 43]) and were allocated via block randomization into one of three experimental groups (with equal numbers of samples from each donor allocated into each group). Each experimental group consisted of 20 bone cube samples. Samples irradiated in dry ice were subjected to irradiation doses ranging from 26.7 kGy to 27.1 kGy (mean 26.9 kGy) at a deep-freezing temperature below -40°C (the recommended long-term storage temperature for allografts). Samples irradiated in gel ice underwent irradiation doses ranging from 26.2 kGy and 26.4 kGy (mean 26.3 kGy) in a freezing temperature range between -40°C and 0°C. Acting as controls, samples in a third group were not subjected to gamma irradiation. The mechanical properties (0.2% offset yield stress, ultimate compression stress, toughness, and the Young modulus) of samples from each group were subsequently evaluated via axial compression loading to failure along the long axis of the bone. The investigators were blinded to sample group during compression testing. RESULTS: The mean ultimate compression stress (84 ± 27 MPa versus 119 ± 31 MPa, mean difference 35 [95% CI 9 to 60]; p = 0.005) and toughness (3622 ± 1720 kJ/m3 versus 5854 ± 2900 kJ/m3, mean difference 2232 [95% CI 70 to 4394]; p = 0.009) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than in those irradiated at deep-freezing temperatures (below -40°C). The mean 0.2% offset yield stress (73 ± 28 MPa versus 109 ± 38 MPa, mean difference 36 [95% CI 11 to 60]; p = 0.002) and ultimate compression stress (84 ± 27 MPa versus 128 ± 40 MPa, mean difference 44 [95% CI 17 to 69]; p < 0.001) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than the nonirradiated control group samples. The mean 0.2% offset yield stress (73 ± 28 MPa versus 101 ± 28 MPa, mean difference 28 [95% CI 3 to 52]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to those irradiated at deep-freezing temperature. The mean toughness (3622 ± 1720 kJ/m3 versus 6231 ± 3410 kJ/m3, mean difference 2609 [95% CI 447 to 4771]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to the non-irradiated control group samples. The mean 0.2% offset yield stress, ultimate compression stress, and toughness of samples irradiated in deep-freezing temperatures (below -40°C) were not different with the numbers available to the non-irradiated control group samples. The Young modulus was not different with the numbers available among the three groups. CONCLUSION: In this study, maintenance of a deep-freezing temperature below -40°C, using dry ice as a cooling agent, consistently mitigated the adverse effects of irradiation on the monotonic-compression mechanical properties of human cortical bone tissue. Preserving the mechanical properties of a cortical allograft, when irradiated in a deep-freezing temperature, may have resulted from attenuation of the deleterious, indirect effects of gamma radiation on its collagen architecture in a frozen state. Immobilization of water molecules in this state prevents radiolysis and the subsequent generation of free radicals. This hypothesis was supported by an apparent loss of the protective effect when a range of higher freezing temperatures was used during irradiation. CLINICAL RELEVANCE: Deep-freezing temperatures below -40°C during gamma irradiation may be a promising approach to better retain the native mechanical properties of cortical bone allografts. A further study of the effect of deep-freezing during gamma radiation sterilization on sterility and other important biomechanical properties of cortical bone (such as, tensile strength, fracture toughness, and fatigue) is needed to confirm these findings.

Aumento da hiperdensidade da cortical óssea línguo-basal após radioterapia em região de cabeça e pescoço: relato de caso / Hyperdensity of the lingual-basal bone cortex incresead after radiotherapy in the head and neck region: case report

Objetivo: relatar um caso de aumento da hiperdensidade da cortical óssea línguo-basal pós-radioterapia em região de cabeça e pescoço por meio de avaliação imaginológica. Relato de caso: paciente do sexo feminino, 80 anos, procurou tratamento odontológico com a finalidade de reabilitação oral com implantes dentários. Na anamnese, relatou histórico de carcinoma espinocelular em regiões distintas da cavidade oral. No exame clínico, notou-se que a paciente era edêntula total e foi solicitado um exame de tomografia computadorizada de feixe cônico. Foi observado, na região anterior inferior, aumento da hiperdensidade da cortical óssea línguo-basal, com osso compacto mais espesso, achado incomum na literatura após radioterapia. Considerações finais: os efeitos da radioterapia em mandíbula estão relatados na literatura. No caso clínico em questão, detectou-se uma alteração pouco notada em pacientes submetidos à radioterapia, fazendo surgir novos questionamentos, sendo eles sobre o diagnóstico dessa modificação na estrutura óssea e suas repercussões. (AU)

Objective: to report a case of increased hyperdensity of the lingual-basal bone cortex after radiotherapy in the head and neck region by means of imaging evaluation. Case report: female patient, 80 years old, sought dental treatment for the purpose of oral rehabilitation with dental implants. In the anamnesis, she reported a history of squamous cell carcinoma in different regions of the oral cavity. Upon clinical examination, it was noted that the patient was total edentulous and a cone beam computed tomography examination was requested. An increase in the hyperdensity of the lingual-basal bone cortex was observed in the lower anterior region, with thicker compact bone, an unusual finding in the literature after radiotherapy. Final considerations: the effects of radiotherapy on the mandible are reported in the literature. In the clinical case in question, a little-noticed change was detected in patients undergoing radiotherapy, leading to new questions, concerning the diagnosis of this change in bone structure and its repercussions.(AU)

Method for Accurately Preparing Cavities on Cortical Bones Using Picosecond Laser.

Objective: This study was conducted to (1) evaluate a new method for accurately and automatically preparing dental implant cavities; (2) investigate the quantitative relationships between the number of focal-plane additive pulse layers (n) in two-dimensional ablation, the Z-axis feed rate, and the ablation depth (d) during cortical-bone ablation using a numerically controlled three-axis picosecond laser; and (3) establish appropriate methods for precise ablation control. Materials and methods: Two-dimensional ablation was performed on swine-rib blocks in the focal plane on a preset circular path using a picosecond laser device and an in-house-developed three-axis numerically controlled micro-laser galvanometer scanner. The maximum two-dimensional d and the quantitative relationship between n and d within the maximum d were consequently obtained. The measured and theoretical values of the ablated cavities were then compared to obtain n and d values corresponding to the minimum difference, and to evaluate the error in d, resulting in a higher-accuracy d value (i.e., single-step ablation depth) being obtained. Results: The diameter and deep errors between the measured and design data for 24 cavities were 2.76 ± 1.51 and 10.23 ± 4.82 µm, respectively. Thus, high-quality cortical-bone cavities preparation was achieved using a picosecond laser with the parameters employed in this study. Conclusions: Precise control of cortical-bone ablation using a picosecond laser can be attained by optimizing the single-step ablation parameters.

Unloading-Induced Cortical Bone Loss is Exacerbated by Low-Dose Irradiation During a Simulated Deep Space Exploration Mission.

Spaceflight-induced bone losses have been reliably reproduced in Hind-Limb-Unloading (HLU) rodent models. However, a considerable knowledge gap exists regarding the effects of low-dose radiation and microgravity together. Ten-week-old male C57BL/6J mice, randomly allocated to Control (CONT), Hind-Limb Unloading (HLU), and Hind-Limb Unloading plus Irradiation (HLUIR), were acclimatized at 28 °C, close to thermoneutral temperature, for 28 days prior to the 14-day HLU protocol. HLUIR mice received a 25 mGy dose of X-ray irradiation, simulating 14 days of exposure to the deep space radiation environment, on day 7 of the HLU protocol. Trabecular bone mass was similarly reduced in HLU and HLUIR mice when compared to CONT, with losses driven by osteoclastic bone resorption rather than changes to osteoblastic bone formation. Femoral cortical thickness was reduced only in the HLUIR mice (102 µm, 97.5-107) as compared to CONT (108.5 µm, 102.5-120.5). Bone surface area was also reduced only in the HLUIR group, with no difference between HLU and CONT. Cortical losses were driven by osteoclastic resorption on the posterior endosteal surface of the distal femoral diaphysis, with no increase in the numbers of dead osteocytes. In conclusion, we show that low-dose radiation exposure negatively influences bone physiology beyond that induced by microgravity alone.

Cortical Thinning and Structural Bone Changes in Non-Human Primates after Single-Fraction Whole-Chest Irradiation.

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

Longitudinal Effects of Single Hindlimb Radiation Therapy on Bone Strength and Morphology at Local and Contralateral Sites.

Radiation therapy (RTx) is associated with increased risk for late-onset fragility fractures in bone tissue underlying the radiation field. Bone tissue outside the RTx field is often selected as a "normal" comparator tissue in clinical assessment of fragility fracture risk, but the robustness of this comparison is limited by an incomplete understanding of the systemic effects of local radiotherapy. In this study, a mouse model of limited field irradiation was used to quantify longitudinal changes in local (irradiated) and systemic (non-irradiated) femurs with respect to bone density, morphology, and strength. BALB/cJ mice aged 12 weeks underwent unilateral hindlimb irradiation (4 × 5 Gy) or a sham procedure. Femurs were collected at endpoints of 4 days before treatment and at 0, 1, 2, 4, 8, 12, and 26 weeks post-treatment. Irradiated (RTx), Contralateral (non-RTx), and Sham (non-RTx) femurs were imaged by micro-computed tomography and mechanically tested in three-point bending. In both the RTx and Contralateral non-RTx groups, the longer-term (12- to 26-week) outcomes included trabecular resorption, loss of diaphyseal cortical bone, and decreased bending strength. Contralateral femurs generally followed an intermediate response compared with RTx femurs. Change also varied by anatomic compartment; post-RTx loss of trabecular bone was more profound in the metaphyseal than the epiphyseal compartment, and cortical bone thickness decreased at the mid-diaphysis but increased at the metaphysis. These data demonstrate that changes in bone quantity, density, and architecture occur both locally and systemically after limited field irradiation and vary by anatomic compartment. Furthermore, the severity and persistence of systemic bone damage after limited field irradiation suggest selection of control tissues for assessment of fracture risk or changes in bone density after radiotherapy may be challenging. © 2017 American Society for Bone and Mineral Research.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice.

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

The effect of ribose pre-treatment of cortical bone on γ-irradiation sterilization effectiveness.

Reconstruction of large skeletal defects is a significant and challenging issue. Tissue banks often use γ-irradiation (15-35 kGy) to sterilize bone allografts, which, however, drastically impairs the post-yield mechanical properties. In previous studies, we reported the development of a method that protects human bone collagen connectivity through ribose crosslinking while still undergoing γ-irradiation. Given these promising results, the next step was to determine if the presence of ribose within the bone tissue would interfere with the effectiveness of the γ-irradiation sterilization against bacteria. This study had two stages. The aim of the first stage was to assess the protective effect of ribose in solution using a Bacillus pumilus spore strip model. The aim of the second stage was to assess the protective effect of ribose (R) on spores within a human cortical bone model in comparison to conventionally irradiated bone (I). Treatment of B. pumilus spore strips with ribose in solution led to temperature-dependent effects on spore viability versus spore strips treated with PBS alone. Ribose solution at 60 °C led to a notable two logs decrease in spore count relative to PBS at 60 °C. In the human bone model, the number of spores in the I and R groups were greatly decreased in comparison to the non-irradiated N group. No spore colonies were detected in the R group (n = 4) whereas two of the four plates of group I formed colonies. This study provides evidence that the method of pre-treating bone with ribose crosslinking prior to irradiation sterilization, while improving irradiation sterilized bone allograft quality, also may improve the effectiveness of the sterilization process.

Investigation of piezoelectric anisotropy of bovine cortical bone at an ultrasound frequency by coupling an experiment and a simulation.

An investigation of the piezoelectric anisotropy of bovine cortical bone at 1 MHz was attempted by coupling data obtained from an experiment and a simulation. In the experiment, a piezoelectric cell (PE-cell) was used as an ultrasound receiver. In the PE-cell, the cortical bone disk, which was cut in the direction perpendicular to the bone axis, was electrically shielded. The directivity of the PE-cell was measured at 0°-22.5° and was compared to four simulated results using the piezoelectric finite-difference time-domain method. It was shown that the piezoelectric signal in the bone could be generated by a transverse ultrasound wave.

Exposure to Low-Dose X-Ray Radiation Alters Bone Progenitor Cells and Bone Microarchitecture.

Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P < 0.05). We evaluated the differentiation capacity of bone marrow stromal cells harvested at days 3 and 21 postirradiation into osteoblast and adipocyte cells. Osteoblast and adipocyte differentiation was decreased when cells were harvested at day 3 postirradiation but enhanced in cells isolated at day 21 postirradiation, suggesting a compensatory recovery process. Osteoclast differentiation was increased in 1 Gy irradiated BMSCs harvested at day 3 postirradiation, but not in those harvested at day 21 postirradiation, compared to controls. This study provides evidence of an early, radiation-induced decrease in osteoblast activity and numbers, as well as a later recovery effect after exposure to 1 Gy of X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.

Raman spectral markers of collagen denaturation and hydration in human cortical bone tissue are affected by radiation sterilization and high cycle fatigue damage.

BACKGROUND: Thermal denaturation and monotonic mechanical damage alter the organic and water-related compartments of cortical bone. These changes can be detected using Raman spectroscopy. However, less is known regarding Raman sensitivity to detect the effects of cyclic fatigue damage and allograft sterilization doses of gamma radiation. OBJECTIVE: To determine if Raman spectroscopic biomarkers of collagen denaturation and hydration are sensitive to the effects of (a) high cycle fatigue damage and (b) 25kGy irradiation. METHODS: Unirradiated and gamma-radiation sterilized human cortical bone specimens previously tested in vitro under high-cycle (> 100,000 cycles) fatigue conditions at 15MPa, 25MPa, 35MPa, 45MPa, and 55MPa cyclic stress levels were studied. Cortical bone Raman spectral profiles from wavenumber ranges of 800-1750cm-1 and 2700-3800cm-1 were obtained and compared from: a) non-fatigue vs fatigue fracture sites and b) radiated vs. unirradiated states. Raman biomarker ratios 1670/1640 and 3220/2949, which reflect collagen denaturation and organic matrix (mainly collagen)-bound water, respectively, were assessed. One- and two-way ANOVA analyses were utilized to identify differences between groups along with interaction effects between cyclic fatigue and radiation-induced damage. RESULTS: Cyclic fatigue damage resulted in increases in collagen denaturation (1670/1640: 1.517 ± 0.043 vs 1.579 ± 0.021, p < 0.001) and organic matrix-bound water (3220/2949: 0.109 ± 0.012 vs 0.131 ± 0.008, p < 0.001). Organic matrix-bound water increased secondary to 25kGy irradiation (3220/2949: 0.105 ± 0.010 vs 0.1161 ± 0.009, p = 0.003). Organic matrix-bound water was correlated positively with collagen denaturation (r = 0.514, p < 0.001). CONCLUSIONS: Raman spectroscopy can detect the effects of cyclic fatigue damage and 25kGy irradiation via increases in organic matrix (mainly collagen)-bound water. A Raman measure of collagen denaturation was sensitive to cyclic fatigue damage but not 25kGy irradiation. Collagen denaturation was correlated with organic matrix-bound water, suggesting that denaturation of collagen to gelatinous form may expose more binding sites to water by unwinding the triple alpha chains. This research may eventually be useful to help identify allograft quality and more appropriately match donors to recipients.

[Normal tissue tolerance to external beam radiation therapy: Bone marrow and cortical bone structures]. / Doses dans les organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : os et moelle osseuse.

In patients undergoing external radiation therapy, bone marrow and cortical bone structures are all often neglected as organs at risk. Still, from increased febrile neutropenia risk in patients undergoing chemoradiation for a pelvic tumour to increased risk of vertebral fracture when undergoing hypofractioned stereotactic radiotherapy of a spinal metastasis, adverse effects are frequent and sometimes serious. This literature review first defines the rules for contouring these structures, then the dose constraints currently recommended. This article focuses first on conventional irradiation or intensity modulation radiotherapy considering classical fractionation. Secondly, it focuses on stereotactic radiotherapy. The considered organs will be haematopoietic structures, and bone cortical structures. Current recommendations are summarised in a table.

Simulated space radiation sensitizes bone but not muscle to the catabolic effects of mechanical unloading.

Deep space travel exposes astronauts to extended periods of space radiation and mechanical unloading, both of which may induce significant muscle and bone loss. Astronauts are exposed to space radiation from solar particle events (SPE) and background radiation referred to as galactic cosmic radiation (GCR). To explore interactions between skeletal muscle and bone under these conditions, we hypothesized that decreased mechanical load, as in the microgravity of space, would lead to increased susceptibility to space radiation-induced bone and muscle loss. We evaluated changes in bone and muscle of mice exposed to hind limb suspension (HLS) unloading alone or in addition to proton and high (H) atomic number (Z) and energy (E) (HZE) (16O) radiation. Adult male C57Bl/6J mice were randomly assigned to six groups: No radiation ± HLS, 50 cGy proton radiation ± HLS, and 50 cGy proton radiation + 10 cGy 16O radiation ± HLS. Radiation alone did not induce bone or muscle loss, whereas HLS alone resulted in both bone and muscle loss. Absolute trabecular and cortical bone volume fraction (BV/TV) was decreased 24% and 6% in HLS-no radiation vs the normally loaded no-radiation group. Trabecular thickness and mineral density also decreased with HLS. For some outcomes, such as BV/TV, trabecular number and tissue mineral density, additional bone loss was observed in the HLS+proton+HZE radiation group compared to HLS alone. In contrast, whereas HLS alone decreased muscle mass (19% gastrocnemius, 35% quadriceps), protein synthesis, and increased proteasome activity, radiation did not exacerbate these catabolic outcomes. Our results suggest that combining simulated space radiation with HLS results in additional bone loss that may not be experienced by muscle.

Early dose-dependent cortical thinning of the femoral neck in anal cancer patients treated with pelvic radiation therapy.

BACKGROUND AND PURPOSE: Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤4months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed. RESULTS: Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p<0.05). FN volume receiving ≥40Gy (V40Gy) was a significant predictor of focal cortical thinning ≥30% (p=0.03). A significant decrease in FN trBMD was observed (-6.4% [range -34.4 to 3.3%]; p=0.01). CONCLUSION: Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.

Elastic-plastic fracture toughness and rising JR-curve behavior of cortical bone is partially protected from irradiation-sterilization-induced degradation by ribose protectant.

OBJECTIVE: This study tested the hypothesis that pre-treating cortical bone with ribose would protect the rising fracture resistance curve behavior and crack initiation fracture toughness of both bovine and human cortical bone from the degrading effects of γ-irradiation sterilization. MATERIALS AND METHODS: A ribose pre-treatment (1.8 M for bovine, and 1.2 M for human, in PBS at 60 °C for 24 h) was applied to single-edge notched bending fracture specimens prior to sterilization with a 33 kGy dose of γ-irradiation. Fracture resistance curves were generated with a single specimen method using an optical crack length measurement technique. The effect of the treatment on overall fracture resistance behavior, crack initiation fracture toughness, and tearing modulus was compared with non-irradiated and conventionally irradiation sterilized controls. Hydrothermal isometric tension testing was used to examine collagen network connectivity and thermal stability to explore relationships between collagen network quality and fracture resistance. RESULTS: The ribose pre-treatment successfully protected the crack growth initiation fracture toughness of bovine and human bone by 32% and 63%, respectively. The rising JR-curve behavior was also partially protected. Furthermore, collagen connectivity and thermal stability followed similar patterns to those displayed by fracture toughness. CONCLUSIONS: This paper demonstrates that the fracture toughness of irradiation-sterilized bone tissue can be partially protected with a ribose pre-treatment. This new approach shows potential for the production and clinical application of sterilized allografts with improved mechanical performance and durability.

Effects of high-dose gamma irradiation on tensile properties of human cortical bone: Comparison of different radioprotective treatment methods.

There are growing interests in the radioprotective methods that can reduce the damaging effects of ionizing radiation on sterilized bone allografts. The aim of this study was to investigate the effects of 50kGy (single dose, and fractionated) gamma irradiation, in presence and absence of l-Cysteine (LC) free radical scavenger, on tensile properties of human femoral cortical bone. A total of 48 standard tensile test specimens was prepared from diaphysis of femurs of three male cadavers (age: 52, 52, and 54 years). The specimens were assigned to six groups (n=8) according to different irradiation schemes, i.e.; Control (Non-irradiated), LC-treated control, a single dose of 50kGy (sole irradiation), a single dose of 50kGy in presence of LC, 10 fractions of 5kGy (sole irradiation), and 10 fractions of 5kGy in presence of LC. Uniaxial tensile tests were carried out to evaluate the variations in tensile properties of the specimens. Fractographic analysis was performed to examine the microstructural features of the fracture surfaces. The results of multivariate analysis showed that fractionation of the radiation dose, as well as the LC treatment of the 50kGy irradiated specimens, significantly reduced the radiation-induced impairment of the tensile properties of the specimens (P<0.05). The fractographic observations were consistent with the mechanical test results. In summary, this study showed that the detrimental effects of gamma sterilization on tensile properties of human cortical bone can be substantially reduced by free radical scavenger treatment, dose fractionation, and the combined treatment of these two methods.