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There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.
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PMID:Pathogenesis of bone fragility in women and men. 1204 92

The flow properties of liquid calcium alginate injections were investigated for application in endovascular embolization. Alginate shear properties were assessed with a rheometer and a controlled injection system. The experimental results were used to model the flow properties and predict alginate's flow characteristics within various medical microcatheter delivery systems. The results suggest that alginates undergo shear-thinning effects with increasing shear. A flow comparison of 2.0 wt % alginate and a Newtonian fluid (82 cP) injected from the same microcatheter had similar flow rates at low injection pressure (100 kPa). However, at high injection pressure (2100 kPa), the alginate was injectable at a flow rate 100% higher than was the Newtonian fluid. Further analysis of injections through microcatheters resulted in a flow model for predicting viscosity changes, flow rates, and injection pressures of liquid alginate at medium-to-high shear rates. The predicted injection pressures and flow rates had an average variance of less than 15% from that of the experimental flow data. This study indicates that calcium alginate has the requisite flow properties for successful delivery to vascular lesions via endovascular injection. Possible uses of alginates include treating arteriovenous malformations (AVMs), aneurysms, blood flow to tumors, and vascular hemorrhages.
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PMID:Flow properties of liquid calcium alginate polymer injected through medical microcatheters for endovascular embolization. 1211 43

The chronic excessive hypersecretion of parathyroid hormone (PTH) in primary hyperparathyroidism (PHPT) has significant impact on bone remodeling. Bone turnover increases by about 50%, leading to increased resorption at the endosteal envelope, increased cortical porosity, and thinning of cortical bone. In cancellous bone a different response is seen. Despite stimulation of bone resorption and formation at the tissue level, osteoclastic resorption and osteoblastic bone formation at individual bone multicellular units (BMUs) are reduced. This causes reduced erosion depth, reduced bone formation rate, and decreased thickness of bone structural units (BSUs), and bone balance at individual BMUs is preserved and may even improve. Thus, PHPT causes cortical bone loss. At the same time, however, cancellous bone structure remains unchanged or even improved, which may offset cortical bone loss. This probably explains the preservation of bone mass demonstrated in long-term follow-up studies of patients with mild PHPT (S-Ca2+ < 2.80 mM). In severe cases of PHPT (S-Ca2+ > 3.00 mM), the negative effects on cortical bone may override the positive impact on cancellous bone, and lead to bone loss and increased risk of fracture.
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PMID:Primary hyperparathyroidism: lessons from bone histomorphometry. 1241 84

The influence of chelating agents (disodium ethylenediaminetetraacetate (EDTA) and sodium citrate) on the physicochemical properties of whey protein isolate (WPI)-stabilized oil-in-water emulsions containing calcium chloride was determined. The calcium-binding characteristics of EDTA and citrate at 30 degrees C were characterized in aqueous solutions (20 mM Tris buffer, pH 7.0) by isothermal titration calorimetry (ITC). EDTA and citrate both bound calcium ions in a 1:1 ratio, but EDTA had a much higher binding constant. Oil-in-water emulsions (pH 7.0) were prepared containing 6.94% (w/v) soybean oil, 0.35% (w/v) WPI, 0.02% (w/v) sodium azide, 20 mM Tris buffer, 10 mM CaCl(2), and 0-40 mM chelating agent. The particle size, apparent viscosity, creaming stability, free calcium concentration, and particle surface potential of the emulsions were measured. The chelating agents reduced or prevented droplet aggregation in the emulsions. When they were present above a certain concentration (>3.5 mM EDTA or >5 mM citrate), droplet aggregation was prevented. The reduction of aggregation was indicated by decreases in particle size, shear-thinning behavior, apparent viscosity, and creaming. Emulsions containing chelating agents had lower free calcium concentrations and more negatively charged droplets, indicating that the chelating agents improved emulsion stability by binding calcium ions. EDTA could be used at lower concentrations than citrate because of its higher calcium ion binding constant.
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PMID:Influence of EDTA and citrate on physicochemical properties of whey protein-stabilized oil-in-water emulsions containing CaCl2. 1242 74

My purpose in this article is to restore the histologic appraisal of renal bone disease to the mainstream of bone and mineral metabolism from which it has been separated for many years. Historically, both the two major components were found in varying degrees in most patients, although one or other of them often predominated. For more than 15 years bone biopsy has been used almost exclusively to classify individual patients into hyperparathyroid, osteomalacic, mixed and adynamic categories according to rigid non-overlapping criteria, and remarkably few histologic data have been reported. All metabolic bone diseases result from disordered bone remodeling, the physiologic mechanism for replacing bone that has become too old to carry out its mechanical or metabolic functions. Bone remodeling is not directly concerned with the regulation of plasma calcium, which reflects the level of equilibration at quiescent bone surfaces between systemic and bone extracellular fluid set by parathyroid hormone. The separation of remodeling from homeostasis explains the concurrence of increased turnover and decreased plasma calcium in chronic renal failure; it is the homeostatic system, rather than the remodeling system, which is resistant to parathyroid hormone. The effect of mild hyperparathyroidism is a nonspecific increase in bone turnover, of which the best index is the bone formation rate measured by double tetracycline labeling expressed per unit of bone surface. Increased turnover is always accompanied by increased reversible mineral deficit. In prolonged hyperparathyroidism there is also accelerated irreversible bone loss manifested mainly as thinning of cortical bone, detectable in chronic renal failure before any symptoms, due to increased resorption depth on the endocortical surface. In severe hyperparathyroidism resorbed bone is replaced, not by a lesser quantity of normal bone, but by a mixture of vascular fibrous tissue and woven bone, referred to as osteitis fibrosa. In osteomalacia there is increased accumulation of osteoid, due not to increased turnover, but to prolongation of mineralization lag time, which in conjunction with increased thickness, surface and volume of osteoid is diagnostic. Converting histomorphometric data into category assignment discards most of the useful information, which can be retained by two-dimensional representation of severity. For the hyperparathyroid dimension, bone formation rate measured by double tetracycline labeling expressed per unit of bone surface is the most useful although not ideal. For the osteomalacic dimension a mineralization index was constructed that is unaffected by age or race. In patients with osteitis fibrosa, bone formation rate per unit of bone surface and mineralization index were inversely correlated. For the third dimension a structure/formation index was constructed which increases with age in healthy women and shows weak inverse correlation with bone formation rate. The structure/formation index is lower than normal in patients with osteitis fibrosa, and should be useful in the study of osteopenia in chronic renal failure. Bone formation rate is low in osteomalacia, but some patients have subnormal rates through quite a different mechanism. The frequency of this finding has been overestimated for several reasons: failure to exclude atypical osteomalacia (increased surface and volume but not thickness of osteoid), use of inappropriate reference values, and failure to measure the bone formation rate on endocortical and intracortical surfaces. In healthy women bone formation rate can be zero on the cancellous surface alone. Low bone formation rate is sometimes due to diabetes but most often is the expected response to subnormal parathyroid hormone secretion accompanying an excess of calcium, a situation recognized only recently because of improvement in parathyroid hormone assay methodology. Low cancellous bone formation rate should not increase fracture risk because turnover is much lower in the peripheral than in the central skeleton, and all reports of increased fracture risk are flawed or open to different interpretation. Low bone formation rate is associated with reduced skeletal buffering of calcium and increased soft tissue calcification. This is not a new disease needing its own treatment, however, but represents the final stage of skeletal adaptation to a surfeit of calcium. The concept of adynamic bone disease has been harmful by directing attention away from the most important consequence of over-treatment of hyperparathyroidism.
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PMID:Renal bone disease: a new conceptual framework for the interpretation of bone histomorphometry. 1281 35

Patients with fragility fractures may have abnormalities in bone structural and material properties such as larger or smaller bone size, fewer and thinner trabeculae, thinned and porous cortices, and tissue mineral content that is either too high or too low. Bone models and remodels throughout life; however, with advancing age, less bone is replaced than was resorbed within each remodeling site. Estrogen deficiency at menopause increases remodeling intensity: a greater proportion of bone is remodeled on its endosteal (inner) surface, and within each of the many sites even more bone is lost as more bone is resorbed while less is replaced, accelerating architectural decay. In men, there is no midlife increase in remodeling. Bone loss within each remodeling site proceeds by reduced bone formation, producing trabecular and cortical thinning. Hypogonadism in 20-30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism increase remodeling: more bone is removed from an ever-diminishing bone mass. As bone is removed from the endosteal envelope, concurrent bone formation on the periosteal (outer) bone surface during aging partly offsets bone loss and increases bone's cross-sectional area. Periosteal apposition is less in women than in men; therefore, women have more net bone loss because they gain less on the periosteal surface, not because they resorb more on the endosteal surface. More women than men experience fractures because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition.
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PMID:Invited Review: Pathogenesis of osteoporosis. 1455 75

A new "all aqueous" procedure for the preparation of stable polysaccharide microparticles was developed. The method consists of dispersing a water solution of an amphiphilic alginate derivative (in the current work, alginate substituted with low amounts of dodecyl chains) first fluidified under mechanical stress, into an NaCl solution. The procedure exploits the ability of amphiphilic associative derivatives to form strong hydrogels in the presence of nonchaotropic salts and their shear-thinning/thixotropic properties. Depending on the experimental conditions, the size of the microparticles can be varied from 10 microm to several hundred micrometers. Their mechanical properties can eventually be reinforced by addition of low concentrations of calcium chloride. The resulting microparticles exhibit a better stability than that of plain Ca(2+)-alginate particles, as they are not disrupted when nongelling cations or calcium-sequestering agents are added to the solution. In addition, the particles can be easily redispersed after being centrifuged or freeze-dried.
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PMID:Production of microspheres based on hydrophobically associating alginate derivatives by dispersion/gelation in aqueous sodium chloride solutions. 1470 75

Formation of calcium phosphate on alkali- and heat-treated titanium surfaces was investigated using transmission electron microscopy (TEM). The samples were prepared by immersing the alkali- and heat-treated titanium in a revised simulated body fluid (R-SBF) with the same HCO(3)(-) concentration level as in human blood plasma. The deposition and precipitation on treated titanium surfaces were extracted for TEM examination without thinning process. Electron diffraction of the precipitates revealed that octacalcium phosphate (OCP), instead of hydroxyapatite (HA), directly nucleates from amorphous calcium phosphate. The OCP crystals continuously grew on the titanium surfaces rather than transforming into apatite. Calcium titanate was also identified by electron diffraction. Its role in the formation bioactive calcium phosphate, however, is not clear from this experiment.
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PMID:TEM study of calcium phosphate precipitation on bioactive titanium surfaces. 1473 41

Increased neuronal density, cortical thinning, and alterations of GABAergic interneurons in the prefrontal cortex have been associated with the pathophysiology of schizophrenia. This study used antibodies directed against the calcium-binding proteins, calretinin (CR), parvalbumin (PV), and calbindin (CB) to compare the relative density of subpopulations of GABAergic interneurons in BA9 of the prefrontal cortex from six subjects with schizophrenia and six control subjects matched for age, gender, and postmortem interval. The relative density of interneurons expressing CR, PV, or CB did not differ significantly between subjects with schizophrenia and control subjects. In addition, no change in somal size of immunoreactive (IR) neurons or cortical thickness was observed between the two groups. This study supports previous reports consistently demonstrating no change in the relative density of interneurons expressing CR in the dorsolateral prefrontal cortex in schizophrenia but does not support previous inconsistent findings that the relative density of interneurons expressing PV and CB might be altered in this disorder.
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PMID:Neurons expressing calcium-binding proteins in the prefrontal cortex in schizophrenia. 1475 22

We have investigated the combined effect of ionic calcium and ethanol on the visual creaming behavior and rheology of sodium caseinate-stabilized emulsions (4 wt% protein, 30 vol% oil, pH 6.8, mean droplet diameter 0.4 microm). A range of ionic calcium concentrations, expressed as a calcium/caseinate molar ratio R, was adjusted prior to homogenization and varying concentrations of ethanol were added shortly after homogenization. A stability map was produced on the basis of visual creaming behavior over a minimum period of 8 h for different calcium/caseinate/ethanol emulsion compositions. A single narrow stable (noncreaming) region was identified, indicating limited cooperation between calcium ions and ethanol. The shear-thinning behavior of the caseinate-stabilized emulsions is typical of systems undergoing depletion flocculation. Addition of calcium ions and/or ethanol was found to lead to a pronounced reduction in viscosity and the onset of Newtonian flow. The state of aggregation was correlated with emulsion microstructure from confocal laser scanning microscopy. Time-dependent rheology (18 h) with a density-matched oil phase (1-bromohexadecane) revealed that the visually stable emulsions were time-independent low-viscosity fluids. Surface coverage data showed that increasing amounts of caseinate were associated with the oil-water interface with increasing R and ethanol content. A decrease in free calcium ions in the aqueous phase with moderate increases in R and ethanol content was observed, which is consistent with greater calcium-caseinate binding (aggregation). Ostwald ripening occurred at the high-ethanol emulsion compositions that were stable to depletion flocculation. While the coarsening rate was low, this can account for the cream plug formation observed during gravity creaming experiments. The caseinate emulsion with no ionic calcium or ethanol exhibits depletion flocculation from excess nonadsorbed caseinate submicelles. Addition of calcium ions reduces the submicelle number density via specific calcium-binding in the aqueous phase (fewer, larger calcium-caseinate aggregates) and at the droplet surface (increased surface coverage). Nonspecific ethanol-induced (calcium-dependent) caseinate submicelle aggregation in the bulk phase and on the droplet surface (increased surface coverage) culminates in a reduction in the number density of caseinate submicelles. A narrow window of inhibition of depletion flocculation occurs in systems containing both calcium ions and ethanol, both species combining to aggregate the protein and so reduce the density of free submicelles.
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PMID:Stability and rheology of emulsions containing sodium caseinate: combined effects of ionic calcium and alcohol. 1514 44


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