Use of small animal PET-CT imaging for in vivo assessment of tendon-to-bone healing: A pilot study.

BACKGROUND: The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (µPET) using 18F-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo µPET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model. METHODS: Unilateral autograft ACL reconstruction was performed in six rats. µPET/CT-scans using 18F-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with µCT and histological analysis. RESULTS: SUVs in both bone tunnels showed an increased 18F-Fluoride uptake at 7 days when compared to 14, 21, and 28 days. SUVs showed a gradient on the tibial side, with most bone turnover in the IAA and least in the EAA. At 7, 14, 21, and 28 days, there were significantly higher SUV values in the IAA compared to the EAA (p = .01, < .01, < .01, < .01). SUVs positively correlated with new bone volumetric density obtained with µCT (r = 0.449, p = .013). Volumetric density of newly formed bone detected on µCT correlated with osteoblast numbers observed along the tunnels in histological sections (r = 0.452, p < .016). CONCLUSIONS: Serial in-vivo µPET/CT-scanning has the potential to provide insight into bone turnover and therefore osteoblastic activity during the healing process. As a result, it allows us to directly measure the effect of interventional strategies in tendon-bone healing.

Cartilage Topography Assessment With Local-Area Cartilage Segmentation for Knee Magnetic Resonance Imaging.

OBJECTIVE: Local-area cartilage segmentation (LACS) software was developed to segment medial femur (MF) cartilage on magnetic resonance imaging (MRI). Our objectives were 1) to extend LACS to the lateral femur (LF), medial tibia (MT), and lateral tibia (LT), 2) to compare LACS to an established manual segmentation method, and 3) to visualize cartilage responsiveness over each cartilage plate. METHODS: Osteoarthritis Initiative participants with symptomatic knee osteoarthritis (OA) were selected, including knees selected at random (n = 40) and knees identified with loss of cartilage based on manual segmentation (Chondrometrics GmbH), an enriched sample of 126 knees. LACS was used to segment cartilage in the MF, LF, MT, and LT on sagittal 3D double-echo steady-state MRI scans at baseline and at 2-year follow-up. We compared LACS and Chondrometrics average thickness measures by estimating the correlation in each cartilage plate and estimating the standardized response mean (SRM) for 2-year cartilage change. We illustrated cartilage loss topographically with SRM heatmaps. RESULTS: The estimated correlation between LACS and Chondrometrics measures was r = 0.91 (95% confidence interval [95% CI] 0.86, 0.94) for LF, r = 0.93 (95% CI 0.89, 0.95) for MF, r = 0.97 (95% CI 0.96, 0.98) for LT, and r = 0.87 (95% CI 0.81, 0.91) for MT. Estimated SRMs for LACS and Chondrometrics measures were similar in the random sample, and SRM heatmaps identified subregions of LACS-measured cartilage loss. CONCLUSION: LACS cartilage thickness measurement in the MF and LF and tibia correlated well with established manual segmentation-based measurement, with similar responsiveness to change, among knees with symptomatic knee OA. LACS measurement of cartilage plate topography enables spatiotemporal analysis of cartilage loss in future knee OA studies.

Clinical and radiological assessment of the induced membrane technique using beta-tricalcium phosphate in reconstructive surgery for lower extremity long bone defects.

AIMS: To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (ß-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes. METHODS: A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using ß-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups. RESULTS: There were ten and 25 defects in the femur and tibia, respectively. Median LEFS improved significantly from 8 (IQR 1.5 to 19.3) preoperatively to 63.5 (IQR 57 to 73.3) at final follow-up (p < 0.001). Bone healing was achieved in all limbs, and median time from the second stage to bone healing was six months (IQR 5 to 10). Median time to bone healing, preoperative LEFS, or postoperative LEFS did not differ significantly between the defect size groups or among the treatment groups. CONCLUSION: IMT using ß-TCP provided satisfactory clinical and radiological outcomes for segmental bone defects in the lower limbs; surgical outcomes were not influenced by bone defect size or operated part. Cite this article: Bone Joint J 2021;103-B(3):456-461.

Dose-Dependent Growth Delay of Breast Cancer Xenografts in the Bone Marrow of Mice Treated with 223Ra: The Role of Bystander Effects and Their Potential for Therapy.

The role of radiation-induced bystander effects in radiation therapy remains unclear. With renewed interest in therapy with α-particle emitters, and their potential for sterilizing disseminated tumor cells (DTCs), it is critical to determine the contribution of bystander effects to the overall response so they can be leveraged for maximum clinical benefit. Methods: Female Foxn1nu athymic nude mice were administered 0, 50, or 600 kBq/kg 223RaCl2 to create bystander conditions. At 24 hours after administration, MDA-MB-231 or MCF-7 human breast cancer cells expressing luciferase were injected into the tibial marrow compartment. Tumor burden was tracked weekly via bioluminescence. Results: The MDA-MB-231 xenografts were observed to have a 10-day growth delay in the 600 kBq/kg treatment group only. In contrast, MCF-7 cells had 7- and 65-day growth delays in the 50 and 600 kBq/kg groups, respectively. Histologic imaging of the tibial marrow compartment, α-camera imaging, and Monte Carlo dosimetry modeling revealed DTCs both within and beyond the range of the α-particles emitted from 223Ra in bone for both MCF-7 and MDA-MB-231 cells. Conclusion: Taken together, these results support the participation of 223Ra-induced antiproliferative/cytotoxic bystander effects in delayed growth of DTC xenografts. They indicate that the delay depends on the injected activity and therefore is dose-dependent. They suggest using 223RaCl2 as an adjuvant treatment for select patients at early stages of breast cancer.

Assessment of lower limb rotational profile and its correlation with the tibial tuberosity-trochlea groove distance: A radiological study.

OBJECTIVE: The purpose of our study was to determine whether there is a correlation between the lower limb rotational profile and tibial tuberosity-trochlea groove (TT-TG) distance. DESIGN AND PATIENTS: The computed tomography cross-sectional imaging on 50 patients' lower limbs (100 limbs) was investigated at our institution. The TT-TG distance was measured along with rotational measurements including femoral version (FV), tibial torsion and knee joint rotation angle (KJRA). Patients were divided into two groups. Group 1 had a TT-TG ≥ 20 mm which was considered pathological and group 2 with a non-pathological TT-TG (≤19 mm). Rotational angles were compared between groups. Statistical analysis was performed using the t-test and Mann-Whitney U analysis. RESULTS AND CONCLUSIONS: Our results demonstrated a statistically significant difference in the mean KJRA (p = 0.026) between the pathological (mean = 10.6, standard deviation (SD) = 7.79°) and the non-pathological TT-TG groups (mean = 6.99, SD = 5.06°). A higher mean value for FV and tibial torsion was also demonstrated in patients with a pathological TT-TG (18.2 vs. 13.7, 32.8 vs. 30.9, p > 0.05, respectively). In conclusion, there was a statistically significant higher mean value for the KJRA in patients with a pathological TT-TG. Hence, a lateralized tibial tubercle as demonstrated by an increase in the TT-TG distance may be associated with a coexisting lower limb rotational malalignment.

Welfare assessment of conventional and organic broilers in Denmark, with emphasis on leg health.

The aim of this study was to survey and report the walking ability in broilers housed in both conventional and organic production systems in Denmark. To this end, the authors assessed the walking ability, by using the Bristol scale, in 31 conventional broiler flocks and in 29 organic broiler flocks distributed across Denmark. In addition, assessment of contact dermatitis, leg abnormalities, scratches and plumage cleanliness, as well as postmortem analysis of tibial dyschondroplasia, was performed in conventional broilers. The survey found a prevalence of 77.4 per cent of impaired walking ability (gait score (GS) >0) in conventional broilers and 38.1 per cent in organic broilers. The prevalence of severe lameness (GS >2) was 5.5 per cent and 2.5 per cent for conventional and organic broilers, respectively. The prevalence of tibial dyschondroplasia in conventional broilers was 4.7 per cent. The results on other welfare indicators are also presented for conventional broilers. The results from the present and previous surveys indicate that the prevalence of impaired walking ability in broiler chickens in the Danish conventional production system is high, but the severity has been steadily decreasing over the last 19 years. Furthermore, the results from the survey of organic broilers suggest that lameness is less prevalent and severe in this system relative to conventional production.

Simulation enabled search for explanatory mechanisms of the fracture healing process.

A significant portion of bone fractures fail to heal properly, increasing healthcare costs. Advances in fracture management have slowed because translation barriers have limited generation of mechanism-based explanations for the healing process. When uncertainties are numerous, analogical modeling can be an effective strategy for developing plausible explanations of complex phenomena. We demonstrate the feasibility of engineering analogical models in software to facilitate discovery of biomimetic explanations for how fracture healing may progress. Concrete analogical models-Callus Analogs-were created using the MASON simulation toolkit. We designated a Target Region initial state within a characteristic tissue section of mouse tibia fracture at day-7 and posited a corresponding day-10 Target Region final state. The goal was to discover a coarse-grain analog mechanism that would enable the discretized initial state to transform itself into the corresponding Target Region final state, thereby providing an alternative way to study the healing process. One of nine quasi-autonomous Tissue Unit types is assigned to each grid space, which maps to an 80×80 µm region of the tissue section. All Tissue Units have an opportunity each time step to act based on individualized logic, probabilities, and information about adjacent neighbors. Action causes transition from one Tissue Unit type to another, and simulation through several thousand time steps generates a coarse-grain analog-a theory-of the healing process. We prespecified a minimum measure of success: simulated and actual Target Region states achieve ≥ 70% Similarity. We used an iterative refinement protocol to explore many combinations of Tissue Unit logic and action constraints. Workflows progressed through four stages of analog mechanisms. Similarities of 73-90% were achieved for Mechanisms 2-4. The range of Upper-Level similarities increased to 83-94% when we allowed for uncertainty about two Tissue Unit designations. We have demonstrated how Callus Analog experiments provide domain experts with a fresh medium and tools for thinking about and understanding the fracture healing process.

Assessment of porosity index of the femoral neck and tibia by 3D ultra-short echo-time MRI.

PURPOSE: To measure the porosity index (PI) by ultrashort echo-time magnetic resonance imaging (UTE MRI) of the femoral neck and tibia; assess its correlations with age, gender, and body mass index (BMI); and analyze the PI correlations between both sites to assess whether tibial PI can reflect changes of femoral neck PI. MATERIALS AND METHODS: In all, 68 healthy men and women (mean age, 45.7 ± 15.9 years) underwent 3D UTE MRI (3.0T) of the hip and mid-shaft tibia. PI of the inferior femoral neck cortex and the whole cortex of the tibia were analyzed. Associations between parameters and differences of PIs between men and women, pre- and postmenopausal women were tested. RESULTS: Femoral neck PI was negatively correlated with age (r = -0.385, P = 0.043) and curvilinearly correlated with BMI (R2 = 0.225, P = 0.041) in men. Tibial PI was correlated with BMI (r = -0.477, P = 0.002) in women and age (r = 0.469, P = 0.043) in postmenopausal women, although P = 0.097 (r = 0.403) after adjustment for BMI. Femoral PI was significantly higher in men than in women (P < 0.001). No significant difference in femoral and tibial PI was observed between pre- and postmenopausal women. The femoral neck and tibial PIs were not significantly correlated in any group. CONCLUSION: PIs had some correlations with age, gender, and BMI. Since femoral neck PI was not correlated with tibial PI, the tibia cannot substitute the femoral neck for estimating bone quality. Direct assessment of the femoral neck cortex is needed. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2018;47:820-828.

Tracking the Progression of Osteolytic and Osteosclerotic Lesions in Mice Using Serial In Vivo µCT: Applications to the Assessment of Bisphosphonate Treatment Efficacy.

The metastasis of tumor cells to bone can lead to osteolytic and osteosclerotic lesions, which cause severe, highly-localized bone destruction and abnormal bone apposition, respectively. Accurate quantification of lesion progression is critical to understand underlying mechanisms and assess treatment efficacy; however, standard structural parameters may be insensitive to local changes. We developed methods to quantify osteolytic and osteosclerotic lesions using micro-computed tomography (µCT) within in vivo mouse datasets. Two Balb/c nude datasets were used: (i) bone-homing MDA-MB-231 (osteolytic) cells injected into the left ventricle, treatment with alendronate or vehicle, and weekly µCT (proximal tibia) for 4 weeks, and (ii) MCF7 (osteosclerotic) cells injected into the right tibia and weekly µCT over 12 weeks. After registering images to baseline, osteolytic lesion volume was determined by summing all baseline bone voxels at distances greater than a threshold (150 µm) from the nearest follow-up. Osteosclerotic lesions were determined by measuring the distance from each follow-up surface voxel to the nearest baseline surface and calculating the standard deviation of distance values (SDDT) of the surrounding voxels. Bone mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were determined for comparison. Osteolytic lesions were observed 1 week after tumor cell injection; however, no corresponding BV/TV losses or Sp increases were observed, indicating that standard parameters were unable to detect early metastatic changes. Lesion volume was smaller in the alendronate versus control group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at weeks 3 and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed following injection, providing a potential new measure of osteosclerotic bone apposition. These data show that quantification of local structural change with serial µCT may overcome the limitations of standard mineral and microstructural parameters, and successfully separates metastatic and normal bone turnover. © 2017 American Society for Bone and Mineral Research.

Assessment of fracture risk in proximal tibia with tumorous bone defects by a finite element method.

There has not been a satisfying method to predict the fracture risk in tumorous bone lesions. To tackle this challenge, we used a finite element method to assess the fracture risk in the proximal tibia (pT) when the size and location of the tumorous defects are varied in bone. Towards this end, the circular cortical defects, mimicking the tumorous lesions by forming cortical window defects, with a diameter (Ф) of 20, 30, 40, or 50 mm, are structured on the anteromedial, lateral, posterior wall of pT, which is located 5, 15, and 25 mm below articular margin, respectively. We found that under walking conditions, the Von Mises Stress of each defective tibia model was larger than that of the intact tibia model and also showed a positive linear correlation with the sizes of the defects. A notable fracture risk was not observed until the defect was Ф30 mm or larger. When the defect emerged, the anteromedial wall resisted fracture risk more than the rest of wall. Our results show that the size and location of the bone tumors are important factors affecting the fracture risk of pT. Our findings will be beneficial to clinicians when deciding what treatment to use for pT lesions.

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

OBJECTIVE: The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods. METHODS: OA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed. RESULTS: Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 µm and the medial osteophyte grew by 0.124±0.028 µm3. Excellent agreement was found when automated measurements were compared with manual assessments. CONCLUSION: Our automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies.

Isolated Syndesmosis Diastasis: Computed Tomography Scan Assessment With Arthroscopic Correlation.

PURPOSE: To investigate which method can predict tibiofibular diastasis more accurately among the tibiofibular interval at the ankle joint level or previous parameters taken 1 cm above the joint line. METHODS: An arthroscopic examination was performed in 78 consecutive patients with anterolateral ankle pain. Four different methods were performed to take measurements of the tibiofibular interval using an axial computed tomography (CT) scan under existing arthroscopic diagnosis. Three previously reported parameters were assessed at 1 cm above the joint level. In the first method, 2 measurements were obtained. The anterior measurement was the closest distance between the anterior border of the fibula and anterior tibial tubercle. The posterior measurement was the closest distance between the medial border of the fibula and posterior tibial tubercle. In the second method, an angle between the fibular axis and the line connecting the anterior and posterior tibial tubercle was measured. In the third method, the nearest distance between the line perpendicular to the line connecting the tubercles at the anterior tubercle of the distal tibia and the anterior-most margin of the fibula was measured. The fourth method, which was developed in this study, measured the narrowest tibiofibular distance at the joint level. Data were analyzed using Student's t-test and the receiver operating characteristic curve to make comparisons among 4 CT-based parameters. RESULTS: In the comparison between the patients with arthroscopic diastasis and without diastasis, the posterior parameter in the first method and the narrowest tibiofibular distance at the joint level in the fourth method showed a significant difference (P < .05) The areas under the receiver operating characteristic curve (AUCs) of the anterior and posterior parameter of the first method were 0.58 (95% confidence interval [CI], 0.43-0.73; P = .167) of anterior measurement and 0.6 (95% CI, 0.45-0.75; P = .029) of posterior measurement, respectively. The second and third methods presented AUCs of 0.59 (95% CI, 0.44-0.74; P = .458) and 0.48 (95% CI, 0.33-0.64; P = .987), respectively. The fourth method presented an AUC of 0.86 (95% CI, 0.75-0.94; P = .000). When the syndesmosis was measured at the joint level, 2 mm of syndesmosis interval as a cutoff value showed 76% of sensitivity and 81% of specificity. CONCLUSIONS: Syndesmosis assessment using an axial CT scan at the joint level best correlated with the arthroscopic examination. When there is more than 2 mm of widening in syndesmosis on the axial CT scan at the joint level, there is a high likelihood of diastasis of the distal tibiofibular syndesmosis in patients who are suspicious clinically to have acute or chronic syndesmosis lesion. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

In vivo assessment of a new multifunctional coating architecture for improved Mg alloy biocompatibility.

Magnesium alloys are regarded as potential biodegradable load-bearing biomaterials for orthopedic applications due to their physico-chemical and biomechanical properties. However, their clinical applicability is restricted by their high degradation rate, which limits the physiological reconstruction of the neighbouring tissues. In this work, a multifunctional coating architecture was developed on an AZ31 alloy by conjoining an anodization process with the deposition of a polymeric-based layer consisting of polyether imine reinforced with hydroxyapatite nanoparticles, aiming at improved control of the corrosion activity and biological performance of the Mg substrate. Anodization and coating protocols were evaluated either independently or combined for corrosion resistance and biological behaviour, i.e. the irritation potential and angiogenic capability within a chicken chorioallantoic membrane assay, and bone tissue response following tibia implantation within a rabbit model. Electrochemical impedance spectroscopy (EIS) analysis showed that coated Mg constructs, particularly anodized plus coated with AZ31, exhibited excellent stability compared to the anodized alloy and, particularly, to the bare AZ31. Microtomographic evaluation of the implanted samples correlated with these degradation results. Mg constructs displayed a non-irritating behaviour, and were associated with high levels of vascular ingrowth. Bone ingrowth neighbouring the implanted constructs was observed for all samples, with coated and anodized plus coated samples presenting the highest bone formation. Gene expression analysis suggested that the enhanced bone tissue formation was associated with the boost in osteogenic activity through Runx2 upregulation, following the activation of PGC-1α/ERRα signaling. Overall, the developed multifunctional coatings appear to be a promising strategy to obtain safe and bioactive biodegradable Mg-based implants with potential applications within bone tissue.

Infective complications in tumour endoprostheses implanted after pathological fracture of the limbs.

INTRODUCTION: Pathological fractures represent an adverse prognostic factor in primary and metastatic bone tumours. The purpose of this study was to evaluate the results of tumour silver-coated prosthesis implanted after pathological fractures. MATERIALS AND METHODS: A retrospective analysis was conducted on 30 patients with pathological limb fracture after primary or metastatic bone tumours treated by the same surgeon with wide margin resection and tumour prosthesis implant between 2005 and 2015. Silver-coated prostheses were implanted in 17 patients and uncoated prostheses were implanted in 13 patients. The primary outcome of the study was to evaluate the infective risk, the secondary outcomes were survival and functional level (visual analogue scale [VAS], 36-Item Short Form Health Survey [SF 36], and Musculoskeletal Tumour Society [MSTS] score) obtained at the longest follow-up available. A multivariate analysis was performed considering age, sex, tumour histology, grading and location, resection size, concomitant radiotherapy/chemotherapy, use of mesh for soft tissue reconstruction and local complications (dislocation, relapse, implant breakage). Scanning electron microscopy (SEM) analysis of explanted prosthesis was performed to study the residual silver-coating. RESULTS: The average age of patients in the study was 56.2 years (range 12-78 years). Silver-coated prostheses were implanted in 56.7% of patients, and uncoated tumour prostheses were used in the remaining 43.3%. The mean follow-up was 40.7 months. A total of 26.7% of patients died at a median time of 28.6 months after surgery. The overall rate of complications was 30%, with 16.7% due to infection. A total of 11.8% of the patients treated with silver-coated implants developed infection compared with 23.1% of the patients treated with uncoated tumour prostheses. There were no cases of early infection in the silver-coated prosthesis group, whereas early infection occurred in 66.7% of patients in the uncoated prosthesis group. All the functional outcomes were significantly improved after surgery. None of the other parameters analysed can be considered a significant negative prognostic factor for infection. The SEM analyses showed severe silver-coating degradation 2 years after first implant. No case of silver toxicity was demonstrated. DISCUSSION: There are few papers in the literature about infective complications in tumour prosthesis after pathological fracture. Silver-coated implants showed a protective action against early infection. Late infection rate was similar between the groups, thereby indicating a reduction of antimicrobial activity for the silver-coating over time. CONCLUSIONS: Silver-coated prostheses are a protective factor against early infections in limb salvage surgery after pathological fractures, so may represent the first-choice of implants in this type of surgery.

Bone Mass Distribution of the Distal Tibia in Normal, Osteopenic, and Osteoporotic Conditions: An Ex Vivo Assessment Using HR-pQCT, DXA, and Computational Modelling.

Osteoporosis leads to bone loss and structural deterioration, which increase the risk of fractures. The aim of this study was to characterize the three-dimensional (3D) bone mass distributions of the distal tibia in normal, osteopenic, and osteoporotic conditions. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the 33 % of the distal tibia and local dual-energy X-ray absorptiometry were applied to 53 intact, fresh-frozen tibiae. The HR-pQCTs were graded to assign local T-scores and merged into three equally sized average normal, osteopenic, and osteoporotic surface models. Volumetric bone mineral density (vBMD) was determined using categorized T-scores, volumetric visualization, and virtual bore probes at the dia-, meta-, and epiphyseal sites (T-DIA, T-META, and T-EPI). We observed a distinct 3D bone mass distribution that was gradually uninfluenced by T-score categories. T-DIA was characterized by the lowest bone mass located in the medullary cavity and a wide homogenous cortex containing the maximum vBMD. The T-META showed decreased cortical thickness and maximal vBMD. At the T-EPI, the relatively low vBMD of the mostly trabecular bone was similar to the maximal cortical vBMD in this sub-region. Four trabecular regions of low bone mass were identified in the recesses. The bone content gradually decreased at all sites, whereas the pattern of bone mass distribution remained essentially unchanged, with the exception of disproportionate losses at T-DIA, T-META, and T-EPI that consistently showed increased endocortical, intracortical, and trabecular bone loss. Extra information can be obtained from the specific pattern of bone mass distribution, potential disproportionate bone losses, and method used.

[Establishment and assessment of tibial osteoradionecrosis in rats].

PURPOSE: To establish a rat tibial osteoradionecrosis model and assess the model by observing clinical manifestation and histopathological examinations. METHODS: The right tibia of 6 Sprague Dawley (SD) rats (weighing 200-250 g) was irradiated by a linear accelerator (single fraction 15 Gy, total dose 60 Gy) every second week for four times. Hair and cutaneous changes of the irradiated region were observed one, two, three and four weeks after irradiation, respectively. Histopathological examination was employed to compare the bone tissue between the irradiated region and irradiation-free region. X-ray film was taken to evaluate the bone destruction. SPSS13.0 software package was used for statistical analysis. RESULTS: One week after irradiation, no significant change was observed in the irradiated region. However, the palm of the irradiated limb turned red remarkably in contrast with the opposite one. Two and three weeks after irradiation, trichomadesis was observed in the irradiated region. Four weeks after irradiation, complete trichomadesis and skin ulceration occurred in the irradiated region. In histopathological examinations, hematoxylin-eosin staining showed that bone mass including bone plate thickness, bone marrow cell, bone trabecula decreased significantly in the irradiated region compared with the control side. Moreover, significant bone destruction was found in irradiated group. CONCLUSIONS: We have successfully established a rat tibial model of osteoradionecrosis with radiation at dosage of 60 Gy divided into 4 times.

Assessment of cortical and trabecular bone changes in two models of post-traumatic osteoarthritis.

Subchondral bone is thought to play a significant role in the initiation and progression of the post-traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed-joint traumatic compressive impact model. Twelve weeks post-injury bones were scanned via micro-computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint-wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans.

The longitudinal assessment of osteomyelitis development by molecular imaging in a rabbit model.

INTRODUCTION: Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. METHODS: An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using 18F-FDG as an infection tracer. RESULTS: The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. CONCLUSIONS: This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of 18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model.

A rapid, novel method of volumetric assessment of MRI-detected subchondral bone marrow lesions in knee osteoarthritis.

PURPOSE: To assess reliability and validity of a semi-automated quantitative method for osteoarthritis (OA)-related bone marrow lesion (BML) assessment in the femur and tibia. METHODS: In a cross-sectional study of subjects with knee OA, we examined concurrent criterion and clinical validation of a novel method of semi-automated quantitative BML measurement. The primary outcome was total segmented BML volume in femoral and tibial medial and lateral knee compartments. Criterion validation was examined through comparison of BML volumes with Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring. Clinical validation was examined via associations of tibial and femoral BML volume with the Western Ontario and McMaster University OA Index weight-bearing pain questions. RESULTS: Among the 115 subjects, mean age was 62 years, mean BMI 30.4 (kg/m(2)), 84% were white and 52% male. The intra-class correlation coefficients (ICC) for intra-reader reliability was 0.96 and 0.97 for inter-reader reliability. Significant Spearman's correlations were found between segmented BML volume and WORMS BML scoring for tibial medial (0.75) and lateral (0.73) compartments, and for femoral medial (0.72) and lateral (0.88) compartments. Significant positive associations were found between weight-bearing pain and total femoral BML volume (P < 0.003), but not total tibial BML (P < 0.101). CONCLUSION: We have documented a moderately strong correlation between a novel measurement method of femoral and tibial BML volume and semi-quantitative WORMS scores, providing evidence of criterion validity. The hypothesis that weight-bearing pain was associated with BML volume was confirmed for total femoral BML volume but not total tibial BML volume. The lack of association between tibial BML volume and pain requires further investigation.

Characterization of a novel mouse model of multiple myeloma and its use in preclinical therapeutic assessment.

To aid preclinical development of novel therapeutics for myeloma, an in vivo model which recapitulates the human condition is required. An important feature of such a model is the interaction of myeloma cells with the bone marrow microenvironment, as this interaction modulates tumour activity and protects against drug-induced apoptosis. Therefore NOD/SCIDγc(null) mice were injected intra-tibially with luciferase-tagged myeloma cells. Disease progression was monitored by weekly bioluminescent imaging (BLI) and measurement of paraprotein levels. Results were compared with magnetic resonance imaging (MRI) and histology. Assessment of model suitability for preclinical drug testing was investigated using bortezomib, melphalan and two novel agents. Cells engrafted at week 3, with a significant increase in BLI radiance occurring between weeks 5 and 7. This was accompanied by an increase in paraprotein secretion, MRI-derived tumour volume and CD138 positive cells within the bone marrow. Treatment with known anti-myeloma agents or novel agents significantly attenuated the increase in all disease markers. In addition, intra-tibial implantation of primary patient plasma cells resulted in development of myeloma within bone marrow. In conclusion, using both myeloma cell lines and primary patient cells, we have developed a model which recapitulates human myeloma by ensuring the key interaction of tumour cells with the microenvironment.