Final Report Summary - BONEQUAL (Assessment of bone quality in metabolic bone diseases)
Scientific problem:
About 30 % of all postmenopausal women in the European Union have osteoporosis, and the prevalence continues to increase with the progressively aging population. Effective diagnostics, prevention and treatment are essential.
Objectives:
The aims were to improve the understanding of bone quality in health and disease, with the long term goal to more effectively diagnose early osteoporosis and predict more accurately fracture risk. Specifically, we aim to assess the effects of aging and osteoporosis on structural, compositional and mechanical properties of trabecular bone. To reach our aims, human cadaver material was collected and supplemented with bone biopsies (iliac crest) from clinical patients with different metabolic bone diseases. Additionally, methodological studies to determine relationships between biophysical techniques were conducted with bone tissue from animals.
Findings:
- Assessment of the 3D shape of the proximal femur using a bone mineral density image: A method was developed to estimate the 3D geometrical shape of bone based on a 2D BMD image and a femur shape template (derived from CT images). The volumetric errors resulting from the shape estimation were low. With further development, this method could provide invaluable information on mechanical strength, and e.g. when coupled with dual energy X-ray absorptiometry (DXA) measurements, could ultimately lead to more sensitive diagnosis of osteoporosis.
- MicroCT image resolution affects structural parameters of normal and osteoporotic human trabecular bone differently: Based on bone biopsies of clinical patients and cadavers, we assessed how microCT image resolution affects structural parameters of bone. We hypothesised that image resolution affects bone structural parameters differently in healthy and osteoporotic bone. Bone samples were imaged with a high-resolution microCT. The effect of decreasing image resolution was compared between the normal and osteoporotic samples. The results suggest that structural differences between osteoporotic and normal trabecular bone may not be reliably detected with CT scanners providing voxel sizes above 100 micrometre.
- Infrared spectroscopy indicated altered bone turnover and remodelling activity in osteoporosis and renal osteodystrophy: This study characterised the composition of bone in these diseases by means of Fourier transform infrared spectroscopic imaging (FTIRI). The ROD samples showed lower carbonate content and a lower degree of mineralisation at the edges of the trabeculae. Correlations with histomorphomety suggested that FTIRI parameters of carbonate may be indicative of turnover and remodelling rate of bone. These findings are potentially interesting for future diagnostics applications.
- Cortical bone tissue increases its elastic stiffness but becomes less viscoelastic during early age: In these studies, nanoindentation was applied to determine hardness and reduced modulus, creep, and semi-dynamic testing to quantify changes in viscoelastic properties with age. Cortical bone samples from female rabbits of varying age were examined. The elastic stiffness increased significantly with age, whereas the viscoelastic parameters decreased with age.
Conclusions and socioeconomic impact:
- Developed method to assess 3D bone strength based on a 2D image could lead to more sensitive assessment of fracture risk in osteoporosis.
- Trabecular structural parameters in normal and osteoporotic bone can only be separated with image voxel sizes up to 100 micrometre. This has clinical importance for development and application of quantitative imaging tools.
- Spectroscopic identification of differences in bone composition in patients with renal osteodystrophy suggests this method as a future potential diagnostic tool for metabolic bone diseases.
- Methods to evaluate viscoelastic properties of bone were developed and it was shown that viscoelasticity decreases with age. This may explain increased bone fragility in elderly.
About 30 % of all postmenopausal women in the European Union have osteoporosis, and the prevalence continues to increase with the progressively aging population. Effective diagnostics, prevention and treatment are essential.
Objectives:
The aims were to improve the understanding of bone quality in health and disease, with the long term goal to more effectively diagnose early osteoporosis and predict more accurately fracture risk. Specifically, we aim to assess the effects of aging and osteoporosis on structural, compositional and mechanical properties of trabecular bone. To reach our aims, human cadaver material was collected and supplemented with bone biopsies (iliac crest) from clinical patients with different metabolic bone diseases. Additionally, methodological studies to determine relationships between biophysical techniques were conducted with bone tissue from animals.
Findings:
- Assessment of the 3D shape of the proximal femur using a bone mineral density image: A method was developed to estimate the 3D geometrical shape of bone based on a 2D BMD image and a femur shape template (derived from CT images). The volumetric errors resulting from the shape estimation were low. With further development, this method could provide invaluable information on mechanical strength, and e.g. when coupled with dual energy X-ray absorptiometry (DXA) measurements, could ultimately lead to more sensitive diagnosis of osteoporosis.
- MicroCT image resolution affects structural parameters of normal and osteoporotic human trabecular bone differently: Based on bone biopsies of clinical patients and cadavers, we assessed how microCT image resolution affects structural parameters of bone. We hypothesised that image resolution affects bone structural parameters differently in healthy and osteoporotic bone. Bone samples were imaged with a high-resolution microCT. The effect of decreasing image resolution was compared between the normal and osteoporotic samples. The results suggest that structural differences between osteoporotic and normal trabecular bone may not be reliably detected with CT scanners providing voxel sizes above 100 micrometre.
- Infrared spectroscopy indicated altered bone turnover and remodelling activity in osteoporosis and renal osteodystrophy: This study characterised the composition of bone in these diseases by means of Fourier transform infrared spectroscopic imaging (FTIRI). The ROD samples showed lower carbonate content and a lower degree of mineralisation at the edges of the trabeculae. Correlations with histomorphomety suggested that FTIRI parameters of carbonate may be indicative of turnover and remodelling rate of bone. These findings are potentially interesting for future diagnostics applications.
- Cortical bone tissue increases its elastic stiffness but becomes less viscoelastic during early age: In these studies, nanoindentation was applied to determine hardness and reduced modulus, creep, and semi-dynamic testing to quantify changes in viscoelastic properties with age. Cortical bone samples from female rabbits of varying age were examined. The elastic stiffness increased significantly with age, whereas the viscoelastic parameters decreased with age.
Conclusions and socioeconomic impact:
- Developed method to assess 3D bone strength based on a 2D image could lead to more sensitive assessment of fracture risk in osteoporosis.
- Trabecular structural parameters in normal and osteoporotic bone can only be separated with image voxel sizes up to 100 micrometre. This has clinical importance for development and application of quantitative imaging tools.
- Spectroscopic identification of differences in bone composition in patients with renal osteodystrophy suggests this method as a future potential diagnostic tool for metabolic bone diseases.
- Methods to evaluate viscoelastic properties of bone were developed and it was shown that viscoelasticity decreases with age. This may explain increased bone fragility in elderly.