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New approach to bone strength measurement
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ABSTRACTS / Bone 42 (2008) S17–S110
depression, and their peripheral expression appears limited to adrenal, testis and pancreas. In the hypothalamus, dynorphin is expressed in leptin-responsive neurons and pre-prodynorphin is co-expressed with NPY. The dynorphin system may represent a pathway by which higher processes including stress, reward/ addiction and depression may influence skeletal metabolism. We examined the bone phenotype of Dynorphin knockout mice (Dyn−/−), which lack the pre-prodynorphin gene and thus all five dynorphin peptides. Body weight of Dyn−/− mice was not different to wild type, but adipose mass was reduced. Cancellous bone volume was elevated in Dyn−/− mice compared to wild type (wild type: 8.8± 0.6 vs Dyn−/−: 11.9% ± 1, p b 0.02). Bone resorption was greater in Dyn−/− mice, as indicated by osteoclast surface (7.9% ± 0.7 vs 11.9 ± 0.7, p b 0.01) and osteoclast number (3.3/mm ± 0.3 vs 4.4 ± 0.2, p b 0.05). However, these changes were overridden by an increased mineral apposition rate in Dyn −/− (1.6 mm/d ± 0.1 vs 2.4 ± 0.2, p b 0.02). In contrast, cortical bone was markedly reduced in Dyn−/− mice without change in bone length. By DXA, femoral BMD was reduced (72 mg/cm2 ± 4 vs 60 ± 2, p b 0.05) as was BMC (30 mg ± 2 vs 23 ± 1, p = 0.05). Consistently, pQCT analysis revealed reductions in cortical BMD and BMC across the femur. Importantly, Dyn−/− mice showed reduced central NPY expression, a change shown previously to increase cortical bone mass and no changes in leptin, despite adiposity changes. This study reveals for the first time a connection between the dynorphin system and bone. The loss of dynorphin signalling resulted in a major loss of cortical bone mass which is not explained by the NPY or leptin pathways. This study identifies a novel central mechanism for regulation of bone mass, with potential links to higher brain functions. doi:10.1016/j.bone.2007.12.070
61 New approach to bone strength measurement Antonio Bazarra-Fernández ObGyn, Juan Canalejo University Hospital Trust, La Coruña, Spain The bone is a multidimensional model and bone strength does not only consist of bone mineral density. It is a physical structure having an irregular shape at all scales of measurement between the greatest and the smallest scale and over all with trabecular bone anisotropy. Precise in vivo measurement of trabecular bone mechanical properties is very important. A method for assessing bone mass and anisotropy is essential. Cancellous bone properties constitute another system with microsystems, isotropy and anisotropy and variety of crosssection. Mechanical properties also depend on its morphological organization at the different lower scales The measurement of bone mineral density by dual energy X-ray absorptiometry (DXA) has served as a fit surrogate for the measurement of bone strength. By reason of the two-dimensional nature of DXA, assumptions must be made regarding the tridimensional nature of the bones, dealing with an inference problem from a set of measurements. It is needed to
make inference about certain parameters which help to make predictions of a certain fracture risk. The main limitation for a proper inference is that only 2d information is got from detectors, and therefore all 3d information is lost, as it is integrated out due to the nature of detector. It is necessary to be very careful when using models for data inference, because we obviously will never know the underlying truth contained in the data. Therefore, it is tried to regain some information about the third dimension by building a model of the bone, which assumes axial symmetry and asymmetry. By using a model, to be arranged the parameter of this model in such a way that they best fit the data, so it is only gained information about how good the model can explain the data, but it is not gotten any information of how good this model actually is, and maybe there is a much better model. It is very difficult to make good inference of the bone strength. But there are anisotropic problems too, and therefore we will make different inferences. Therefore it is deduced, that this method seems to be very sensitive to error, and it is necessary to know how to deal with these errors, especially with the systematic errors introduced by using a parameterized model. So, a mathematical, physical and physiological 5-dimensional model must be developed in order to gauge bone properties including geometry(2-dimensional DXA), space, time, motion and stress with a portable-computer-device. doi:10.1016/j.bone.2007.12.071
62 New paradigm: Hydroxyapatite versus calcium carbonate Antonio Bazarra-Fernandez ObGyn, Juan Canalejo University Hospital Trust, Culleredo, Spain Life is a struggle against hydrogen ions. Long-term acid loading in humans causes an increase in renal acid excretion. Proton-pump inhibitors (PPIs), suppress acid production through a different biological mechanism. People taking high doses of PPIs are more likely to break a hip. PPIs interfere with the continuous breakdown and rebuilding of bone. Acid dissolves old or damaged bone, and PPIs limit the acid production. Dietary protein has a magnitude-dependent anabolic effect on bone, because protein supplies the amino acid substrates for building bone matrix. Contemporary Western diets contain acid precursors in excess of base precursors. Consumption of animal protein, grain, and high amounts of milk increases the acidity of the body. Acidosis influences the homeostasis of calcium, partly due to the influence on renal mechanisms. Scant evidence supports nutrition guidelines focused specifically on increasing milk or other dairy product intake for promoting child and adolescent bone mineralization. In humans, essential amino acid supplementation increases circulating concentrations of insulinlike growth hormone. The catabolic effect on bone related to the magnitude of the diet’s net acid load can offset the anabolic effect of higher dietary protein intakes. Sodium chloride, elevates urinary calcium excretion. Higher long-term protein
ABSTRACTS / Bone 42 (2008) S17–S110
depression, and their peripheral expression appears limited to adrenal, testis and pancreas. In the hypothalamus, dynorphin is expressed in leptin-responsive neurons and pre-prodynorphin is co-expressed with NPY. The dynorphin system may represent a pathway by which higher processes including stress, reward/ addiction and depression may influence skeletal metabolism. We examined the bone phenotype of Dynorphin knockout mice (Dyn−/−), which lack the pre-prodynorphin gene and thus all five dynorphin peptides. Body weight of Dyn−/− mice was not different to wild type, but adipose mass was reduced. Cancellous bone volume was elevated in Dyn−/− mice compared to wild type (wild type: 8.8± 0.6 vs Dyn−/−: 11.9% ± 1, p b 0.02). Bone resorption was greater in Dyn−/− mice, as indicated by osteoclast surface (7.9% ± 0.7 vs 11.9 ± 0.7, p b 0.01) and osteoclast number (3.3/mm ± 0.3 vs 4.4 ± 0.2, p b 0.05). However, these changes were overridden by an increased mineral apposition rate in Dyn −/− (1.6 mm/d ± 0.1 vs 2.4 ± 0.2, p b 0.02). In contrast, cortical bone was markedly reduced in Dyn−/− mice without change in bone length. By DXA, femoral BMD was reduced (72 mg/cm2 ± 4 vs 60 ± 2, p b 0.05) as was BMC (30 mg ± 2 vs 23 ± 1, p = 0.05). Consistently, pQCT analysis revealed reductions in cortical BMD and BMC across the femur. Importantly, Dyn−/− mice showed reduced central NPY expression, a change shown previously to increase cortical bone mass and no changes in leptin, despite adiposity changes. This study reveals for the first time a connection between the dynorphin system and bone. The loss of dynorphin signalling resulted in a major loss of cortical bone mass which is not explained by the NPY or leptin pathways. This study identifies a novel central mechanism for regulation of bone mass, with potential links to higher brain functions. doi:10.1016/j.bone.2007.12.070
61 New approach to bone strength measurement Antonio Bazarra-Fernández ObGyn, Juan Canalejo University Hospital Trust, La Coruña, Spain The bone is a multidimensional model and bone strength does not only consist of bone mineral density. It is a physical structure having an irregular shape at all scales of measurement between the greatest and the smallest scale and over all with trabecular bone anisotropy. Precise in vivo measurement of trabecular bone mechanical properties is very important. A method for assessing bone mass and anisotropy is essential. Cancellous bone properties constitute another system with microsystems, isotropy and anisotropy and variety of crosssection. Mechanical properties also depend on its morphological organization at the different lower scales The measurement of bone mineral density by dual energy X-ray absorptiometry (DXA) has served as a fit surrogate for the measurement of bone strength. By reason of the two-dimensional nature of DXA, assumptions must be made regarding the tridimensional nature of the bones, dealing with an inference problem from a set of measurements. It is needed to
make inference about certain parameters which help to make predictions of a certain fracture risk. The main limitation for a proper inference is that only 2d information is got from detectors, and therefore all 3d information is lost, as it is integrated out due to the nature of detector. It is necessary to be very careful when using models for data inference, because we obviously will never know the underlying truth contained in the data. Therefore, it is tried to regain some information about the third dimension by building a model of the bone, which assumes axial symmetry and asymmetry. By using a model, to be arranged the parameter of this model in such a way that they best fit the data, so it is only gained information about how good the model can explain the data, but it is not gotten any information of how good this model actually is, and maybe there is a much better model. It is very difficult to make good inference of the bone strength. But there are anisotropic problems too, and therefore we will make different inferences. Therefore it is deduced, that this method seems to be very sensitive to error, and it is necessary to know how to deal with these errors, especially with the systematic errors introduced by using a parameterized model. So, a mathematical, physical and physiological 5-dimensional model must be developed in order to gauge bone properties including geometry(2-dimensional DXA), space, time, motion and stress with a portable-computer-device. doi:10.1016/j.bone.2007.12.071
62 New paradigm: Hydroxyapatite versus calcium carbonate Antonio Bazarra-Fernandez ObGyn, Juan Canalejo University Hospital Trust, Culleredo, Spain Life is a struggle against hydrogen ions. Long-term acid loading in humans causes an increase in renal acid excretion. Proton-pump inhibitors (PPIs), suppress acid production through a different biological mechanism. People taking high doses of PPIs are more likely to break a hip. PPIs interfere with the continuous breakdown and rebuilding of bone. Acid dissolves old or damaged bone, and PPIs limit the acid production. Dietary protein has a magnitude-dependent anabolic effect on bone, because protein supplies the amino acid substrates for building bone matrix. Contemporary Western diets contain acid precursors in excess of base precursors. Consumption of animal protein, grain, and high amounts of milk increases the acidity of the body. Acidosis influences the homeostasis of calcium, partly due to the influence on renal mechanisms. Scant evidence supports nutrition guidelines focused specifically on increasing milk or other dairy product intake for promoting child and adolescent bone mineralization. In humans, essential amino acid supplementation increases circulating concentrations of insulinlike growth hormone. The catabolic effect on bone related to the magnitude of the diet’s net acid load can offset the anabolic effect of higher dietary protein intakes. Sodium chloride, elevates urinary calcium excretion. Higher long-term protein