Search

Purpose To determine whether patient-specific finite element (FE) computer models are better at assessing fracture risk for femoral bone metastases compared to clinical assessments based on axial cortical involvement on conventional radiographs, as described in current clinical guidelines. Methods Forty-five patients with 50 femoral bone metastases, who were treated with palliative radiotherapy for pain, were included (64% single fraction (8 Gy), 36% multiple fractions (5 or 6 x 4 Gy)) and were followed for six months to determine whether they developed a pathological femoral fracture. All plain radiographs available within a two month period prior to radiotherapy were obtained. Patient-specific FE models were constructed based on the geometry and bone density obtained from the baseline quantitative CT scans used for radiotherapy planning. Femoral failure loads normalized for body weight (BW) were calculated. Patients with a failure load of 7.5 x BW or lower were identified as having high fracture risk, whereas patients with a failure load higher than 7.5 x BW were classified as low fracture risk. Experienced assessors measured axial cortical involvement on conventional radiographs. Following clinical guidelines, patients with lesions larger than 30 mm were identified as having a high fracture risk. FE predictions were compared to clinical assessments by means of diagnostic accuracy values (sensitivity, specificity and positive (PPV) and negative predictive values (NPV)). Results Seven femurs (14%) fractured during follow-up. Median time to fracture was 8 weeks. FE models were better at assessing fracture risk in comparison to axial cortical involvement (sensitivity 100% vs. 86%, specificity 74% vs. 42%, PPV 39% vs. 19%, and NPV 100% vs. 95%, for the FE computer model vs. axial cortical involvement, respectively). Conclusions Patient-specific FE computer models improve fracture risk assessments of femoral bone metastases in advanced cancer patients compared to clinical assessments based on axial cortical involvement, which is currently used in clinical guidelines.

Purpose: Genetic knockout or pharmacological inhibition of the beta-2 adrenergic receptor (B2AR) increased bone mass, whereas stimulation decreased bone mass in rodents. In humans, observational studies support sympathetic nervous system regulation of bone metabolism, but intervention studies are lacking. We aimed to determine the effects of a selective beta-2 adrenergic agonist and non-selective antagonist on human bone metabolism. Methods: 32 healthy postmenopausal women were included in a randomized controlled trial conducted in the Academic Medical Center Amsterdam. Participants were randomized to receive treatment with 17-β estradiol 2. mg/day; 17-β estradiol 2. mg/day and terbutaline 5. mg/day (selective B2AR agonist); propranolol 80. mg/day (non-selective B-AR antagonist); or no treatment during 12. weeks. Main outcome measure was the change in serum concentrations of procollagen type I N propeptide (P1NP) and C-terminal crosslinking telopeptides of collagen type I (CTx) as markers of bone formation and resorption after 12. weeks compared between the treatment groups. Data were analyzed with mixed model analysis. Results: 17-β estradiol decreased bone turnover compared to control (P1NP p.

Contains fulltext : 69065.pdf (Publisher’s version ) (Closed access) The process of bone remodeling is carried out by 'basic multicellular units' of osteoclasts and osteoblasts. Osteoclasts excavate a resorption space that is subsequently filled with new bone by osteoblasts. In cortical bone osteoclasts dig tunnels through solid bone, in cancellous bone they dig trenches across the trabecular surface. Osteoblasts fill these tunnels and trenches, creating osteons and hemi-osteons, respectively. Both the osteons of cortical bone and the trabeculae of cancellous bone are aligned to the dominant loading direction, indicating that BMU's are mechanically regulated. How mechanical forces guide these cells is still uncertain. We hypothesize that strain-induced osteocyte signals inhibit osteoclast activity and stimulate osteoblast activity. This hypothesis was implemented in a finite element-based bone adaptation model, that was extended with a cell simulation model. This allowed us to examine tunneling and trenching by osteoclasts. We found that our simulations capture key features of BMU-based remodeling: (1) cortical BMU's create load-aligned osteons; (2) cancellous BMU's move across the surface of trabeculae instead of piercing them; (3) resorption-formation coupling occurs in response to strains around resorption sites; and (4) resorbing osteoclasts target nearby regions of osteocyte death, thus providing a mechanism for bone repair.

Item does not contain fulltext In this study, we investigate how morphological parameters and mechanical properties derived from microcomputed tomography (microCT) are affected by small errors in threshold value when variable bone structures and different bone volume fractions are involved. For this purpose, biopsies of vertebrae of 6-, 23-, and 230-week-old female pigs were scanned using microCT. For each specimen, five threshold values were determined within the range of thresholds that an observer could select realistically, in steps of 0.5%. The scans were converted to microfinite-element (microFE) models, used to determine the elastic moduli. A variation of 0.5% in threshold resulted in a 5% difference in bone volume fraction and 9% difference in maximal stiffness for bone cubes with a volume fraction of 0.2, these differences were only 2% and 3%, respectively. For all bone cubes, the differences for trabecular thickness and bone surface density were

Item does not contain fulltext In mature trabecular bone, both density and trabecular orientation are adapted to external mechanical loads. Few quantitative data are available on the development of architecture and mechanical adaptation in juvenile trabecular bone. We studied the hypothesis that a time lag occurs between the adaptation of trabecular density and the adaptation of trabecular architecture during development. To investigate this hypothesis we used ten female pigs at 6, 23, 56, 104, and 230 weeks of age. Three-dimensional morphological and mechanical parameters of trabecular bone samples from the vertebra and proximal tibia were studied using microcomputed tomography and micro-finite element analysis. Both bone volume fraction and stiffness increased rapidly in the initial growth phase (from 6 weeks on), whereas the morphological anisotropy started increasing only after 23 weeks of age. In addition, the anisotropy reached its highest value much later in the development than did bone volume fraction. Hence, the alignment of trabeculae was still progressing at the time of peak bone mass. Therefore, our hypothesis was supported by the time lag between the increase in trabecular density and the adaptation of the trabecular architecture. The rapid increase of bone volume fraction in the initial growth phase can be explained by the enormous weight increase of the pigs. The trabeculae aligned at later stages when the increase in weight, and thus the loading, was slowed considerably compared with the early growth stage. Hence, the trabecular architecture was more efficient in later years. We conclude that density is adapted to external load from the early phase of growth, whereas the trabecular architecture is adapted later in the development.