Prediction of risk of fracture in the tibia due to altered bone mineral density distribution resulting from disuse : a finite element study

The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in postmenopausal women and the aged, with decreases in bone mineral density (BMD) leading to weakening of the bone and increased risk of fracture. The aim of the study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate the risk of fracture; comparing between two groups, an able bodied (AB) group and spinal cord injury (SCI) patients group suffering from varying degree of bone loss. The tibiae of eight male subjects with chronic SCI and those of four able-bodied (AB) age-matched controls were scanned using multi-slice peripheral Quantitative Computed Tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions – compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between SCI subjects and their controls. The differences in BMD distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including SCI, multiple sclerosis and the ageing population). The ultimate aim would be to reduce fracture occurrence in these vulnerable groups

骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.博士（医学）・甲第656号・平成28年11月24日© Copyright 2016 American Association of Neurological SurgeonsThe definitive version is available at " http://dx.doi.org/10.3171/2016.8.SPINE16250

Risk of fracture modelling in healthy and osteoporotic tibia

Background: Osteoporosis has detrimental effects on the structural integrity of the skeletal system. The degeneration of bone material can be seen in spinal cord injury (SCI) patients due to lack of mechanical stimulation following extensive muscle paralysis. Aim: The aim of the study was to simulate and compare the mechanical response of the tibia of both able bodied (AB) subjects and SCI patients under four different types of loading, compression, A-P bending, M-L bending and torsion, and map how the risk of fracture (RF) correlated with bone mineral density (BMD) and type of loading. The stress distribution was calculated using the finite element method. Material and methods: Eight male SCI subjects with varying degrees of bone loss and four age-matched AB male control subjects were recruited for the study. The bones were scanned in vivo at the Queen Elizabeth National Spinal Injuries Unit (Glasgow) using a multi-slice peripheral Quantitative Computed Tomography, and individualised three dimensional finite element models were created of each subject's tibia from the scans using Mimics (Materialise). The material assignment was based on the greyscale pixel values of the scan images from which BMD was calculated. An empirical power law was used to estimate the Young’s modulus and the ultimate tensile strength for each element from the BMD. Results: Analysis of the material distribution in the tibia showed large numbers of elements with low BMD for the SCI group whereas a larger proportion of high density bone was seen in the AB group. The average BMD was lower at the epiphyses for the SCI group, but overall little difference was seen around the diaphysis between the groups. The finite element modelling was carried out using Abaqus (v.6.11, Simulia). The analysis was performed using 4 node tetrahedral elements and the element density was on average 2.9 elements/mm^3. The von Mises stress values of each element were exported and the percentage of elements exceeding an estimated RF threshold calculated. The results showed an increase in percentage of elements exceeding the RF threshold for the SCI group in bending and torsion compared to compression which is in agreement with clinical experience. On average, the SCI group showed greater numbers of elements exceeding the RF threshold than the AB group for all four loading conditions. The majority of the fractured elements were located around the epiphyses for all subjects. Conclusions and clinical implications: Using the analysis methods described can provide clinicians with useful patient-specific information about the amount of loading that can be put safely on the osteoporotic bone. That is of importance in SCI patient rehabilitation where musculoskeletal rehabilitation techniques include stimulating the bone via mechanical methods such as vibration or electrical stimulation of the muscles. Using such subject-specific analysis it is possible to determine the location along the bone that is most likely to fail along with the risk associated