Osteo-cise: Strong Bones for Life: protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures

Background : Osteoporosis affects over 220 million people worldwide, and currently there is no \u27cure\u27 for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition. Methods : The \u27Osteo-cise: Strong Bones for Life\u27 study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function, and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged 60 years or above will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month \u27research to practise\u27 translational phase. Participants will be randomly assigned to either the \u27Osteo-cise\u27 intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed. Discussion : The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture.<br /

Mechanical properties of femoral trabecular bone in dogs

BACKGROUND: Studying mechanical properties of canine trabecular bone is important for a better understanding of fracture mechanics or bone disorders and is also needed for numerical simulation of canine femora. No detailed data about elastic moduli and degrees of anisotropy of canine femoral trabecular bone has been published so far, hence the purpose of this study was to measure the elastic modulus of trabecular bone in canine femoral heads by ultrasound testing and to assess whether assuming isotropy of the cancellous bone in femoral heads in dogs is a valid simplification. METHODS: From 8 euthanized dogs, both femora were obtained and cubic specimens were cut from the centre of the femoral head which were oriented along the main pressure and tension trajectories. The specimens were tested using a 100 MHz ultrasound transducer in all three orthogonal directions. The directional elastic moduli of trabecular bone tissue and degrees of anisotropy were calculated. RESULTS: The elastic modulus along principal bone trajectories was found to be 11.2 GPa ± 0.4, 10.5 ± 2.1 GPa and 10.5 ± 1.8 GPa, respectively. The mean density of the specimens was 1.40 ± 0.09 g/cm(3). The degrees of anisotropy revealed a significant inverse relationship with specimen densities. No significant differences were found between the elastic moduli in x, y and z directions, suggesting an effective isotropy of trabecular bone tissue in canine femoral heads. DISCUSSION: This study presents detailed data about elastic moduli of trabecular bone tissue obtained from canine femoral heads. Limitations of the study are the relatively small number of animals investigated and the measurement of whole specimen densities instead of trabecular bone densities which might lead to an underestimation of Young's moduli. Publications on elastic moduli of trabecular bone tissue present results that are similar to our data. CONCLUSION: This study provides data about directional elastic moduli and degrees of anisotropy of canine femoral head trabecular bone and might be useful for biomechanical modeling of proximal canine femora

A new anisotropy index on trabecular bone radiographic images using the fast Fourier transform

BACKGROUND: The degree of anisotropy (DA) on radiographs is related to bone structure, we present a new index to assess DA. METHODS: In a region of interest from calcaneus radiographs, we applied a Fast Fourier Transform (FFT). All the FFT spectra involve the horizontal and vertical components corresponding respectively to longitudinal and transversal trabeculae. By visual inspection, we measured the spreading angles: Dispersion Longitudinal Index (DLI) and Dispersion Transverse Index (DTI) and calculated DA = 180/(DLI+DTI). To test the reliability of DA assessment, we synthesized images simulating radiological projections of periodic structures with elements more or less disoriented. RESULTS: Firstly, we tested synthetic images which comprised a large variety of structures from highly anisotropic structure to the almost isotropic, DA was ranging from 1.3 to 3.8 respectively. The analysis of the FFT spectra was performed by two observers, the Coefficients of Variation were 1.5% and 3.1 % for intra-and inter-observer reproducibility, respectively. In 22 post-menopausal women with osteoporotic fracture cases and 44 age-matched controls, DA values were respectively 1.87 ± 0.15 versus 1.72 ± 0.18 (p = 0.001). From the ROC analysis, the Area Under Curve (AUC) were respectively 0.65, 0.62, 0.64, 0.77 for lumbar spine, femoral neck, total femoral BMD and DA. CONCLUSION: The highest DA values in fracture cases suggest that the structure is more anisotropic in osteoporosis due to preferential deletion of trabeculae in some directions

Processing and analysis of in-vivo high-resolution MR images of trabecular bone for longitudinal studies: reproducibility of structural measures and micro-finite element analysis derived mechanical properties

The authors have developed a system for the characterization of trabecular bone structure from high-resolution MR images. It features largely automated coil inhomogeneity correction, trabecular bone region segmentation, serial image registration, bone/marrow binarization, and structural calculation steps. The system addresses problems of efficiency and inter- and intraoperator variability inherent in previous analyses. The system is evaluated on repetitive scans of 8 volunteers for both two-dimensional (2D) apparent structure calculations and three-dimensional (3D) mechanical calculations using micro-finite element analysis. Coil correction methods based on a priori knowledge of the coil sensitivity and on low-pas! s filtering of the high-resolution mages are compared and found to perform similarly. Image alignment is found to cause small but significant changes in some structural parameters. Overall the automated system provides on the order of a 3-fold decrease in trained operator time over previous manual methods. Reproducibility is found to be dependent on image quality for most parameters. For 7 subjects with good image quality, reproducibility of 2-4% is found for 2D structural parameters, while 3D mechanical parameters vary by 4-9%, with percent standardized coefficients of variation in the ranges of 15-34% and 20-38% respectively

High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after one year of idoxifene treatment

Objective. To investigate whether recently developed in vivo high-resolution magnetic resonance-imaging and micro-finite element techniques can monitor changes in bone mechanical properties during long-term clinical trials aiming at evaluating the efficacy of new drugs for the treatment of osteoporosis.Design. Comparison of baseline and follow-up mechanical parameters calculated using micro-finite element analysis of the calcaneus for subjects participating in a study investigating the effect of idoxifene.Background. Contemporary measurements for the evaluation of bone mechanical properties, based on dual-energy X-ray absorptiometry measurements, are not very accurate and require large! trial populations.Methods. A total of 56 postmenopausal subjects received either a placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the calcaneus were made at baseline and after one year. Mechanical parameters of a trabecular volume of interest in the calcaneus were calculated using micro-finite element analysis.Results. Although there were no significant differences between the mean changes in the treated groups and the placebo group, there were significant changes from baseline within groups after one year of treatment. Significant changes, however, were found only for mechanical parameters and only in the treated groups.Conclusions. The present study is the first demonstration that longitudinal changes in bone mechanical properties due to trabecular micro-architectural changes may be quantified in long-term clinical studies. Since significant changes in mechanical parameters were obtained for the treated groups whereas no ! significant change in bone mass was found we conclude that the application of these techniques may increase the clinical significance of these trials.Relevance A precise diagnosis of in vivo bone mechanical properties that accounts for (changes in) trabecular bone architecture is of particular importance for longitudinal clinical trials aiming at evaluating the efficacy of new drugs since it can lead to clinically relevant results from shorter follow-up intervals and may enable a reduction of the number of patients involved in the trial

P2-09-12: High Resolution Diffusion MRI Characterizes Tumor Stromal Boundaries.

Abstract Background: Studies of 3D cell cultures have shown that mammary epithelial cell growth and morphogenesis is regulated by extracellular matrix (ECM) stiffness, linking ECM stiffening to malignant transformation. Tumors are consistently stiffer than normal adjacent tissue, and matrix stiffening is caused by ECM cross-linking and increased deposition of collagen. Some evidence suggests that collagen orientation at tumor boundaries can promote tumor metastasis. Measuring the stiffness of the tumor boundaries and adjacent stromal tissue may give additional information 1) about tumor microenvironment and 2) to guide treatment. Diffusion-weighted imaging (DWI) MRI measures the mobility of water in tissue and may be sensitive to this phenomenon. Material and Methods: MRI data was collected on patients with locally advance breast cancer enrolled in an IRB-approved study at UCSF and signed informed consent. In addition to a standard dynamic contrast enhanced (DCE) MRI, a high-resolution diffusion-weighted image (HR DWI) was acquired with an echo planar imaging sequence and the following parameters: TR/TE=4000/64.8 ms, b=0,600, FOV=70×140mm, matrix=28×64, and voxel size=0.55×0.55×4.0mm. Apparent diffusion coefficient (ADC) maps were created. HR DWI images were segmented into tumor and non-enhancing, surrounding stromal tissue. A proximity mapping method was used to measure ADC values at the inner edge of tumor and at increasing distances from the tumor boundary on HR DWI. The mean was calculated for the voxels in 1 mm increments, starting at 5 mm into the tumor (−5 mm) and ending at 2.5 cm away from the tumor (25 mm). Results: The average of the changes per 1 mm shell was largest for the transition of the tumor boundary (Table 1). In Table 1, the −5 to 0 mm, 0 to 5 mm, and 5 to 25 mm columns represent inside the tumor, tumor boundary, and outside the tumor, respectively. In general, ADC values were consistently lower inside the tumor than outside. The greatest changes per 1 mm shell was seen in the transition from inside to outside tumor, although the values varied among tumor types. Each of the three cases analyzed had different patterns of ADC values. Discussion: These preliminary studies show that water mobility measurements change at the tumor boundary, with different patterns observed among individual patients. We are further investigating the influence of density and tumor margin morphology on these ADC measurements. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-12.</jats:p

Comparison of MRI tumor volumetric and diameter measurements for predicting recurrence free survival in breast cancer patients undergoing preoperative chemotherapy.

Abstract Abstract #6053 Background: Assessment of tumor response to chemotherapy has traditionally relied on the bidimensional tumor measurement guidelines proposed by the World Health Organization (WHO, 1979) and more recently on the unidimensional Response Evaluation Criteria in Solid Tumors (RECIST, Therasse et al., 2000). MRI is being used increasingly to monitor breast cancer response to preoperative chemotherapy and allows both linear and volumetric assessment of tumor size. The purpose of this study was to compare pre- and post-treatment RECIST, WHO, and volumetric measures of tumor size on MRI for predicting recurrence free survival (RFS) in patients undergoing preoperative chemotherapy.&amp;#x2028; Materials &amp; Methods: 56 patients with locally advanced breast cancer were imaged with MRI (1.5T GE scanner) before and after 4 cycles of preoperative chemotherapy. Tumor longest diameter (LD) at physical exam (ClinLD) was recorded before (N=56) and after (N=48) treatment. Fat suppressed, contrast enhanced, T1-weighted sagittal 3DFGRE images (TE/TR=8/4.2ms, flip=20°, 2mm thick, 18-20cm FOV, 256x192 matrix) were acquired for tumor size measurements.&amp;#x2028; All MRI LD measurements were made manually following RECIST and WHO guidelines. Tumor volume was measured with a semi-automated tumor segmentation algorithm based on a specific enhancement ratio calculation. Univariate Cox proportional hazards analysis was used to assess the value of clinical, pathology, RECIST, WHO, and volume measurements for predicting RFS. Variables with p&amp;lt;0.15 were combined in a stepwise multivariate model to determine the greatest predictive value.&amp;#x2028; Results: 23 patients have recurred since surgery (mean time 132 weeks). The mean RFS in the non-recurrent group is 330 weeks. Results for univariate and multivariate analysis are show in the Table. Final tumor volume was most predictive of recurrence free survival, and was the only variable found to be an independent significant predictor in the multivariate analysis. Age, tumor grade, and positive lymph node status were not significant predictors.&amp;#x2028; Discussion: Post-chemotherapy tumor volume calculated via a semi-automatic algorithm was found to be a significant predictor of RFS for patients undergoing preoperative chemotherapy, out-performing manual 1D RECIST, 2D WHO, and clinical measurements. The results support previous work demonstrating the value of MRI tumor volume for predicting patient outcome.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6053.</jats:p

Artificial intelligence and imaging biomarkers for prostate radiation therapy during and after treatment

Magnetic resonance imaging (MRI) is increasingly used in the management of prostate cancer (PCa). Quantitative MRI (qMRI) parameters, derived from multi-parametric MRI, provide indirect measures of tumour characteristics such as cellularity, angiogenesis and hypoxia. Using Artificial Intelligence (AI), relevant information and patterns can be efficiently identified in these complex data to develop quantitative imaging biomarkers (QIBs) of tumour function and biology. Such QIBs have already demonstrated potential in the diagnosis and staging of PCa. In this review, we explore the role of these QIBs in monitoring treatment response during and after PCa radiotherapy (RT). Recurrence of PCa after RT is not uncommon, and early detection prior to development of metastases provides an opportunity for salvage treatments with curative intent. However, the current method of monitoring treatment response using prostate-specific antigen levels lacks specificity. QIBs, derived from qMRI and developed using AI techniques, can be used to monitor biological changes post-RT providing the potential for accurate and early diagnosis of recurrent disease