Separate modeling of cortical and trabecular bone offers little improvement in FE predictions of local structural stiffness at the proximal tibia

Abstract

Quantitative computed tomography-based finite element (QCT-FE) modeling has potential to clarify the role of altered subchondral bone stiffness in osteoarthritis. The objective of this research was to evaluate different QCT-FE modeling and thresholding approaches to identify the method which best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. Our results showed that separate modeling of proximal tibial cortical and trabecular bone offered little improvement in QCT-FE-predicted stiffness (0% to +3% improvement in explained variance) when compared to modeling the proximal tibia as a single structure. Based on the results of this study, we do not recommend separate modeling of cortical bone and trabecular bone when developing QCT-FE models of the proximal tibia for predicting subchondral bone stiffness.     

Development of a surrogate model based on patient weight,bone mass and geometry to predict femoral neck strains and fracture loads

Osteoporosis and related bone fractures are an increasing global burden in our ageing society. Areal bone mineral density assessed through dual energy X-ray absorptiometry (DEXA), the clinically accepted and most used method, is not sufficient to assess fracture risk individually. Finite element (FE) modelling has shown improvements in prediction of fracture risk, better than aBMD from DEXA, but is not practical for widespread clinical use. The aim of this study was to develop an adaptive neural network (ANN)-based surrogate model to predict femoral neck strains and fracture loads obtained from a previously developed population-based FE model. The surrogate model performance was assessed in simulating two loading conditions: the stance phase of gait and a fall.The surrogate model successfully predicted strains estimated by FE (r² = 0.90–0.98 for level gait load case, r² = 0.92–0.96 for the fall load case). Moreover, an ANN model based on three measurements obtainable in clinics (femoral neck length (level gait) or maximum femoral neck diameter (fall), femoral neck bone mass, body weight) was able to give reasonable predictions (r² = 0.84–0.94) for all of the strain metrics and the estimated femoral neck fracture load. Overall, the surrogate model has potential for clinical applications as they are based on simple measures of geometry and bone mass which can be derived from DEXA images, accurately predicting FE model outcomes, with advantages over FE models as they are quicker and easier to perform.     

Experimental validation of finite element predicted bone strain in the human metatarsal

Metatarsal stress fracture is a common injury observed in athletes and military personnel. Mechanical fatigue is believed to play an important role in the etiology of stress fracture, which is highly dependent on the resulting bone strain from the applied load. The purpose of this study was to validate a subject-specific finite element (FE) modeling routine for bone strain prediction in the human metatarsal. Strain gauge measurements were performed on 33 metatarsals from seven human cadaveric feet subject to cantilever bending, and subject-specific FE models were generated from computed tomography images. Material properties for the FE models were assigned using a published density-modulus relationship as well as density-modulus relationships developed from optimization techniques. The optimized relationships were developed with a ‘training set’ of metatarsals (n = 17) and cross-validated with a ‘test set’ (n = 16). The published and optimized density elasticity equations provided FE-predicted strains that were highly correlated with experimental measurements for both the training (r² ≥ 0.95) and test (r² ≥ 0.94) sets; however, the optimized equations reduced the maximum error by 10% to 20% relative to the published equation, and resulted in an X = Y type of relationship between experimental measurements and FE predictions. Using a separate optimized density-modulus equation for trabecular and cortical bone did not improve strain predictions when compared to a single equation that spanned the entire bone density range. We believe that the FE models with optimized material property assignment have a level of accuracy necessary to investigate potential interventions to minimize metatarsal strain in an effort to prevent the occurrence of stress fracture.     

Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone – An experimental and finite element study

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n = 11, male, age 18–78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (E_eq) increased with increasing crystallinity (r = 0.730, p = .011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r = 0.718, p = .019). In addition, the normalized shear modulus g₁ (r = −0.780, p = .005) decreased with increasing collagen ratio (amide III/CH₂) at the tissue-level, but increased (r = 0.696, p = .025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only E_eq, g₂ and relaxation time τ₁ from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p < .01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone.     

A nonlinear finite element model validation study based on a novel experimental technique for inducing anterior wedge-shape fractures in human vertebral bodies in vitro

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R² improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae.     

Spectral K-edge subtraction imaging of experimental non-radioactive barium uptake in bone

PurposeTo evaluate the feasibility of using non-radioactive barium as a bone tracer for detection with synchrotron spectral K-edge subtraction (SKES) technique.MethodsMale rats of 1-month old (i.e., developing skeleton) and 8-month old (i.e., skeletally mature) were orally dosed with low dose of barium chloride (33 mg/kg/day Ba²⁺) for 4 weeks. The fore and hind limbs were dissected for imaging in projection and computed tomography modes at 100 μm and 52 μm pixel sizes. The SKES method utilizes a single bent Laue monochromator to prepare a 550 eV energy spectrum to encompass the K-edge of barium (37.441 keV), for collecting both ‘above’ and ‘below’ the K-edge data sets in a single scan.ResultsThe SKES has a very good focal size, thus limits the ‘crossover’ and motion artifacts. In juvenile rats, barium was mostly incorporated in the areas of high bone turnover such as at the growth plate and the trabecular surfaces, but also in the cortical bone as the animals were growing at the time of tracer administration. However, the adults incorporated approximately half the concentration and mainly in the areas where bone remodeling was predominant and occasionally in the periosteal and endosteal layers of the diaphyseal cortical bone.ConclusionsThe presented methodology is simple to implement and provides both structural and functional information, after labeling with barium, on bone micro-architecture and thus has great potential for in vivo imaging of pre-clinical animal models of musculoskeletal diseases to better understand their mechanisms and to evaluate the efficacy of pharmaceuticals.     

A combined passive and active musculoskeletal model study to estimate L4-L5 load sharing

A number of geometrically-detailed passive finite element (FE) models of the lumbar spine have been developed and validated under in vitro loading conditions. These models are devoid of muscles and thus cannot be directly used to simulate in vivo loading conditions acting on the lumbar joint structures or spinal implants. Gravity loads and muscle forces estimated by a trunk musculoskeletal (MS) model under twelve static activities were applied to a passive FE model of the L4-L5 segment to estimate load sharing among the joint structures (disc, ligaments, and facets) under simulated in vivo loading conditions. An equivalent follower (FL), that generates IDP equal to that generated by muscle forces, was computed in each task. Results indicated that under in vivo loading conditions, the passive FE model predicted intradiscal pressures (IDPs) that closely matched those measured under the simulated tasks (R² = 0.98 and root-mean-squared-error, RMSE = 0.18 MPa). The calculated equivalent FL compared well with the resultant force of all muscle forces and gravity loads acting on the L4-L5 segment (R² = 0.99 and RMSE = 58 N). Therefore, as an alternative approach to represent in vivo loading conditions in passive FE model studies, this FL can be estimated by available in-house or commercial MS models. In clinical applications and design of implants, commonly considered in vitro loading conditions on the passive FE models do not adequately represent the in vivo loading conditions under muscle exertions. Therefore, more realistic in vivo loading conditions should instead be used.     

Subchondral bone microarchitecture and failure mechanism under compression: A finite element study

Subchondral bone (SCB) microdamage is commonly observed in traumatic joint injuries and has been strongly associated with post-traumatic osteoarthritis (PTOA). Knowledge of the three-dimensional stress and strain distribution within the SCB tissue helps to understand the mechanism of SCB failure, and may lead to an improved understanding of mechanisms of PTOA initiation, prevention and treatment. In this study, we used high-resolution micro-computed tomography (µCT)-based finite element (FE) modelling of cartilage-bone to evaluate the failure mechanism and the locations of SCB tissue at high-risk of initial failure under compression. The µCT images of five cartilage-bone specimens with an average SCB thickness of 1.23 ± 0.20 mm were used to develop five µCT-based FE models. The FE models were analysed under axial compressions of approximately 30 MPa applied to the cartilage surface while the bone edges were constrained. Strain and stress-based failure criteria were then applied to evaluate the failure mechanism of the SCB tissue under excessive compression through articular cartilage. µCT-based FE models predicted two locations in the SCB at high-risk of initial failure: (1) the interface of the calcified-uncalcified cartilage due to excessive tension, and (2) the trabecular bone beneath the subchondral plate due to excessive compression. µCT-based FE models of cartilage-bone enabled us to quantify the distribution of the applied compression which was transferred through the articular cartilage to its underlying SCB, and to investigate the mechanism and the mode of SCB tissue failure. Ultimately, the results will help to understand the mechanism of injury formation in relation to PTOA.     

Cervical spine posteroanterior stiffness differs with neck position

PurposeSpinal stiffness is commonly considered when treating patients with neck pain, but there are few studies reporting the objective measurement of cervical spine stiffness or the possible kinesiological factors that may affect its quantification. The aim of this study was to determine if the position of the neck affects cervical spine stiffness.MethodsAn instrumented stiffness assessment device measured posteroanterior cervical spine stiffness at C4 of 25 prone-lying asymptomatic subjects in three neck positions in randomised order: maximal flexion, maximal extension, and neutral. The device applied five standardised mechanical oscillatory pressures while measuring the applied force and concurrent displacement, defining stiffness as the slope of the linear portion of the force–displacement curve. Repeated measures analysis of variance with Bonferroni-adjusted post hoc comparisons determined whether stiffness differed between neck positions.ResultsThere was a significant difference in cervical spine stiffness between different neck positions (F_(1.6,38.0) = 16.6, P < 0.001). Stiffness was least in extension with a mean of 3.09 N/mm (95% CI 2.59, 3.58) followed by neutral (3.94, 95% CI 3.49, 4.39), and then flexion (4.32, 95% CI 3.96, 4.69).ConclusionWhen assessing cervical spine stiffness, neck position should be standardised to ensure maximal reliability and utility of stiffness judgments.     

Noninvasive prediction of vertebral body compressive strength using nonlinear finite element method and an image based technique

Noninvasive prediction of vertebral body strength under compressive loading condition is a valuable tool for the assessment of clinical fractures. This paper presents an effective specimen-specific approach for noninvasive prediction of human vertebral strength using a nonlinear finite element (FE) model and an image based parameter based on the quantitative computed tomography (QCT). Nine thoracolumbar vertebrae excised from three cadavers with an average age of 42 years old were used as the samples. The samples were scanned using the QCT. Then, a segmentation technique was performed on each QCT sectional image. The segmented images were then converted into three-dimensional FE models for linear and nonlinear analyses. A new material model was implemented in our nonlinear model being more compatible with real mechanical behavior of trabecular bone. A new image based MOS (Mechanic of Solids) parameter named minimum sectional strength ((σ_uA)_min) was used for the ultimate compressive strength prediction. Subsequently, the samples were destructively tested under uniaxial compression and their experimental ultimate compressive strengths were obtained. Results indicated that our new implemented FE model can predict ultimate compressive strength of human vertebra with a correlation coefficient (R² = 0.94) better than usual linear and nonlinear FE models (R² = 0.83 and 0.85 respectively). The image based parameter introduced in this study ((σ_uA)_min) was also correlated well with the experimental results (R² = 0.86). Although nonlinear FE method with new implemented material model predicts compressive strength better than the (σ_uA)_min, this parameter is clinically more feasible due to its simplicity and lower computational costs. This can make future applications of the (σ_uA)_min more justified for human vertebral body compressive strength prediction.     

Distal skeletal tibia assessed by HR-pQCT is highly correlated with femoral and lumbar vertebra failure loads

Dual energy X-ray absorptiometry (DXA) is the standard for assessing fragility fracture risk using areal bone mineral density (aBMD), but only explains 60–70% of the variation in bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides 3D-measures of bone microarchitecture and volumetric bone mineral density (vBMD), but only at the wrist and ankle. Finite element (FE) models can estimate bone strength with 86–95% precision. The purpose of this study is to determine how well vBMD and FE bone strength at the wrist and ankle relate to fracture strength at the hip and spine, and to compare these relationships with DXA measured directly at those axial sites. Cadaveric samples (radius, tibia, femur and L4 vertebra) were compared within the same body. The radius and tibia specimens were assessed using HR-pQCT to determine vBMD and FE failure load. aBMD from DXA was measured at the femur and L4 vertebra. The femur and L4 vertebra specimens were biomechanically tested to determine failure load. aBMD measures of the axial skeletal sites strongly correlated with the biomechanical strength for the L4 vertebra (r = 0.77) and proximal femur (r = 0.89). The radius correlated significantly with biomechanical strength of the L4 vertebra for vBMD (r = 0.85) and FE-derived strength (r = 0.72), but not with femur strength. vBMD at the tibia correlated significantly with femoral biomechanical strength (r = 0.74) and FE-estimated strength (r = 0.83), and vertebral biomechanical strength for vBMD (r = 0.97) and FE-estimated strength (r = 0.91). The higher correlations at the tibia compared to radius are likely due to the tibia’s weight-bearing function.     

Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model

PurposeTo investigate the accuracy of predicted time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK) model.MethodsPBPK parameters were estimated using biokinetic data of 15 patients after injection of (152 ± 15) MBq of ¹¹¹In-DTPAOC (total peptide amount (5.78 ± 0.25) nmol). True mathematical phantoms of patients (MPPs) were the PBPK model with the estimated parameters. Dynamic PET measurements were simulated as being done after bolus injection of 150 MBq ⁶⁸Ga-DOTATATE using the true MPPs. Dynamic PET scans around 35 min p.i. (P₁), 4 h p.i. (P₂) and the combination of P₁ and P₂ (P₃) were simulated. Each measurement was simulated with four frames of 5 min each and 2 bed positions. PBPK parameters were fitted to the PET data to derive the PET-predicted MPPs. Therapy was simulated assuming an infusion of 5.1 GBq of ⁹⁰Y-DOTATATE over 30 min in both true and PET-predicted MPPs. TIACs of simulated therapy were calculated, true MPPs (true TIACs) and predicted MPPs (predicted TIACs) followed by the calculation of variabilities v.ResultsFor P₁ and P₂ the population variabilities of kidneys, liver and spleen were acceptable (v < 10%). For the tumours and the remainders, the values were large (up to 25%). For P₃, population variabilities for all organs including the remainder further improved, except that of the tumour (v > 10%).ConclusionTreatment planning of PRRT based on dynamic PET data seems possible for the kidneys, liver and spleen using a PBPK model and patient specific information.     

Préconditionnement laser en site osseux membraneux : mise au point d’un modèle d’étude

ObjectiveThe application of a supraphysiologic stress (preconditioning) prior to an injury induces cellular and tissular resistance on soft tissues. The aim of this study is to evaluate X-ray irradiated bone healing with and without laser preconditioning.Materials and methodsThe laser shot is defined to induce a controlled increase of the bone temperature. Then, bone healing is in vivo observed through the evolution of the vascularization process. Optical chambers implanted on the skull of 20 rabbits allow the weekly observation of bone vascular plexus during 12 weeks. An original image processing determines the vascular density (VD) on four groups: #1: control group (n = 5); #2: laser treatment (n = 5); #3: X-ray irradiation (n = 5); #4: laser preconditioning prior to X-ray irradiation (n = 5).ResultsPreconditioning is performed by a diode-laser (815 nm, 36 J/cm²). VD remains stable during the 12-week follow up for groups #1 and #2. X-ray radiation induces a significant decrease of the vascular network in groups #3 and #4 compared to the group #1 (p < 0.001). However, the decrease of the vascularization is limited in group #4 versus group #3 (p < 0.05).DiscussionThis in vivo original model reproducibly evaluates VD and the impact of different stresses on bone healing. Laser treatment is a controlled heating method, which preserves the vascular network of X-ray irradiated bone. This innovative approach promotes the bone healing in which the vascular supply has been damaged.     

Volume to density relation in adult human bone tissue

Uniformity of tissue mineralisation is a strongly debated issue, due to its relation with bone mechanical behaviour. Bone mineral density (BMD) is measured in the clinical practice and is applied in computational application to derive material proprieties of bone tissue. However, BMD cannot identify if the variation in bone density is related to a modification of tissue mineral density (TMD), a change in bone volume or a combination of the two. This study was aimed to investigate whether TMD can be assumed as a constant in adult human bone (trabecular and cortical).A total number of 115 cylindrical bone specimens were collected. An inter-site analysis (96 specimens, 2 donors) was performed on cortical and trabecular specimens extracted from different anatomical sites. An intra-site study (19 specimens, 19 donors) was performed on specimens extracted from femoral heads. Bone volume fraction (BV/TV) was computed by means of a micro-computed tomography. Furthermore, ash density (ρ_ash) was measured. TMD was computed as the ratio between ρ_ash and BV/TV.It was found that the TMD of trabecular (1.24±0.16 g/cm³) and cortical (1.19±0.06 g/cm³) bone were not statistically different (p=0.31). Furthermore, the linear regression between ρ_ash and BV/TV was statistically significant (r²=0.99, p<0.001). Intra- and inter-site analyses demonstrated that the mineral distribution was independent of the extraction site.The present study suggests that TMD can be assumed reasonably constant in non-pathological adult bone tissue. Consequently, it is suggested that TMD can be managed as a constant in computational models, varying only BV in relation to clinical densitometric analysis.     

Immunosuppressant FK506 decreases the intracellular magnesium in the human osteoblast cell by inhibiting the ERK1/2 pathway

AimsPrevious studies reported that FK506 influences bone mineralizing and hypomagnesemia, and also has immune modifying properties. This study examined whether or not the function of Mg²⁺ in bone metabolism plays a role in the loss of bone volume caused by immunosuppressants.Main methodsThe effects of the FK506 treatment on the intracellular magnesium and lactate dehydrogenase (LDH) activity were examined in cultured human osteoblasts (HOB) cells. The magnesium concentration was determined using microfluorescence techniques and atomic absorption spectrophotometry. Western blotting was used to measure the level of extracellular signal-regulated kinases 1/2 (ERK 1/2) activation.Key findingsFK506 (0.1 μM) did not affect cell death in HOB cells after a 24 hour treatment but decreased the level of ERK 1/2 activation. In HOB cells, the mean [Mg²⁺]i after exposure to a 1 mM extracellular Mg²⁺ ([Mg²⁺]o) buffer was 0.53 ± 0.01 mM (n = 25). Exposure to 100 nM FK506 produced a significant decrease in [Mg²⁺]i (0.41 ± 0.01 mM). The ERK inhibitor (PD98059) and FK506 produced similar effects but they were not cumulative.SignificanceThis study examined the role of ERK1/2 activation on the regulation of magnesium in HOB. These results suggest that the inhibition of ERK phosphorylation is an essential intermediate in the effects of FK506 on magnesium. Overall, FK506 causes bone disorders partly by decreasing [Mg²⁺]i accompanied by the inhibition of ERK 1/2.     

Eye lens dose correlations with personal dose equivalent and patient exposure in paediatric interventional cardiology performed with a fluoroscopic biplane system

PurposeTo analyse the correlations between the eye lens dose estimates performed with dosimeters placed next to the eyes of paediatric interventional cardiologists working with a biplane system, the personal dose equivalent measured on the thorax and the patient dose.MethodsThe eye lens dose was estimated in terms of H_p(0.07) on a monthly basis, placing optically stimulated luminescence dosimeters (OSLDs) on goggles. The H_p(0.07) personal dose equivalent was measured over aprons with whole-body OSLDs. Data on patient dose as recorded by the kerma-area product (P_KA) were collected using an automatic dose management system. The 2 paediatric cardiologists working in the facility were involved in the study, and 222 interventions in a 1-year period were evaluated. The ceiling-suspended screen was often disregarded during interventions.ResultsThe annual eye lens doses estimated on goggles were 4.13 ± 0.93 and 4.98 ± 1.28 mSv. Over the aprons, the doses obtained were 10.83 ± 0.99 and 11.97 ± 1.44 mSv. The correlation between the goggles and the apron dose was R² = 0.89, with a ratio of 0.38. The correlation with the patient dose was R² = 0.40, with a ratio of 1.79 μSv Gy⁻¹ cm⁻². The dose per procedure obtained over the aprons was 102 ± 16 μSv, and on goggles 40 ± 9 μSv. The eye lens dose normalized to P_KA was 2.21 ± 0.58 μSv Gy⁻¹ cm⁻².ConclusionsMeasurements of personal dose equivalent over the paediatric cardiologist’s apron are useful to estimate eye lens dose levels if no radiation protection devices are typically used.     

Comparison of 68GA-FAPI-04 PET/CT and 18F-FDG PET/CT in detection of metastatic bone disease in various cancers

ObjectiveOur aim in this retrospective study was to compare the diagnostic accuracy of ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT in detecting bone metastases of various cancers and to evaluate the potential usefulness of ⁶⁸Ga-FAPI-04 PET/CT in detecting metastatic bone disease.Material and methodOur retrospective study included 44 patients diagnosed with bone metastases due to various cancers between January 2021 and February 2022. All patients underwent ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT imaging within 14 days. In the semi-quantitative analysis of the skeletal system, all regions with higher uptake than background activity were considered pathological. SUVmax and Metastasis-to-background ratio (TBR) values were calculated from metastatic sites.ResultsA total of 827 bone metastases were detected in our study. The diagnostic accuracies of FAPI PET/CT and ¹⁸F-FDG PET/CT were 91.8% and 81.5%, respectively (P < 0.001). When all bone metastases were compared, the SUVmax of ⁶⁸Ga-FAPI-04 PET/CT was statistically significantly higher than that of ¹⁸F-FDG PET/CT (median 6.15 vs. 5.2; P < 0.001). When FDG and FAPI SUVmax values were compared according to metastasis types, FAPI SUVmax and TBR values in osteolytic, medullary and mixed type bone metastases were found to be statistically significantly higher than FDG (P-values: < 0.001, < 0.001, < 0.001, respectively). There was no statistically significant difference between FDG and FAPI SUVmax values in osteoblastic bone metastases (P = 0.26).ConclusionIt has been shown that ⁶⁸Ga-FAPI-04 PET/CT is superior to ¹⁸F-FDG PET/CT in detecting metastatic bone disease and may have more clinical impact on disease management.     

Expression of the Androgen Receptor,pAkt, and pPTEN in Breast Cancer and Their Potential in Prognostication

BACKGROUNDImportance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.METHODSThis study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82).RESULTSExpression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P < .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR⁺ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR^? tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR⁺ /pAkt⁺ /pPTEN^? tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR^?/pAkt⁺/pPTEN^? tumors (Mean OS = 5.1 ± 0.738 years).CONCLUSIONAR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa.     

The impact of state of bladder fullness on tonic and phasic activation of the pelvic floor muscles in women

PurposeWe aimed to determine if state of bladder fullness affects pelvic floor muscle activation in healthy women without urogenital symptoms.Materials and methodsTwenty-three nulliparous, continent female participants were recruited to participate. Women were randomized to begin the protocol with either an empty (EF) or a full (FE) bladder. Tonic and maximal voluntary pelvic floor muscle electromyographic activity were measured in three states of bladder fullness (empty, full and uncomfortably full). Electromyographic signal amplitudes were compared among bladder states using separate two-way repeated-measures analyses of variance including bladder state and test order as main effects as well as the interaction between bladder state and test order.ResultsTonic activity of the pelvic floor muscles was significantly higher in the full and uncomfortably full bladder states compared to when the bladder was empty (p < 0.005). Maximum voluntary electromyographic activation was unaffected by state of bladder fullness (p = 0.713).ConclusionsConsistent with studies in which the bladder was filled through saline infusion, these results suggest that tonic activity of the PFMs is higher when the bladder is full compared to when it is empty. However once the bladder is moderately full, tonic PFM activity does not increase with increases in bladder volume.     

Intramedullary pressure and matrix strain induced by oscillatory skeletal muscle stimulation and its potential in adaptation

Intramedullary pressure (ImP) and low-level bone strain induced by oscillatory muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia, i.e., hindlimb suspension (HLS). To test this hypothesis, we evaluated (a) MS-induced ImP and bone strain as function of stimulation frequency and (b) the adaptive responses to functional disuse, and disuse plus 1 and 20 Hz stimulation in vivo. Femoral ImP and bone strain generated by MS were measured in the frequencies of 1–100 Hz in four rats. Forty retired breeder rats were used for the in vivo HLS study. The quadriceps muscle was stimulated at frequencies of 1 and 20 Hz, 10 min/d for four weeks. The metaphyseal trabecular bone quantity and microstructure at the distal femur were evaluated using μCT, while bone formation indices were analyzed using histomorphometric technique. Oscillatory MS generated a maximum ImP of 45±9 mmHg at 20 Hz and produced a maximum matrix strain of 128±19 με at 10 Hz. Our analyses from the in vivo study showed that MS at 20 Hz was able to attenuate trabecular bone loss and partially maintain the microstructure induced by HLS. Conversely, there was no evidence of an adaptive effect of stimulation at 1 Hz on disused skeleton. The results suggested that oscillatory MS regulates fluid dynamics and mechanical strain in bone, which serves as a critical mediator of adaptation. These results clearly demonstrated the ability of MS in attenuating bone loss from the disuse osteopenia, which may hold potential in mitigating skeletal degradation imposed by conditions of disuse, and may serve as a biomechanical intervention in clinic application.