This review summarizes and updates data presented at recent annual Southern Medical Association conferences on postmenopausal osteoporosis. As part of any osteoporosis treatment program, it is important to maintain adequate calcium and 25-hydroxyvitamin D levels either through diet or supplementation. Among the available pharmacologic therapies, the bisphosphonates alendronate and risedronate have demonstrated the most robust fracture risk reductions- approximately 40 to 50% reduction in vertebral fracture risk, 30 to 40% in nonvertebral fracture risk, and 40 to 60% in hip fracture risk. Ibandronate, a new bisphosphonate, has demonstrated efficacy in reducing vertebral fracture risk. Salmon calcitonin nasal spray and raloxifene demonstrated significant reductions in vertebral fracture risk in pivotal studies. Teriparatide significantly reduced vertebral and nonvertebral fracture risk. Drugs on the horizon include strontium ranelate, which has been shown to reduce vertebral and nonvertebral fracture risk, and zoledronic acid, an injectable bisphosphonate that increased bone density with once-yearly administration.

Osteoporosis is characterized by chronic bone loss and deterioration of microarchitecture that can leave patients more susceptible to costly and debilitating fractures. A variety of treatment options have been developed that target different cells and pathways to disrupt its progression. In addition to pharmaceutical options, regular exercise is recommended, as external, mechanical loading has long been recognized as a stimulus bone can use to regulate its size and shape to meet mechanical demands. While bone cell signaling is undoubtedly multifaceted, meaningful changes in bone mass ultimately result from the actions of bone-forming osteoblasts and bone-resorbing osteoclasts. To this end, therapies are most traditionally described through their impacts on these cells, and are broadly categorized as anabolic (activating osteoblasts and having bone-building effects, such as parathyroid hormone injections and sclerostin antibody treatment), or anti-resorptive (targeting osteoclasts and slowing resorption, such as bisphosphonates and denosumab). Bone formation and resorption are rooted in two overarching processes: coupled bone remodeling (resorption followed by formation in the same space) and uncoupled bone modeling (formation or resorption occurring independently). Hematopoietic-lineage cells have an inherent, established role in bone remodeling, as descendent osteoclasts perform the resorption to initiate remodeling, but have only more recently been implicated as potential orchestrators of anabolic bone modeling in their preosteoclastic states, suggesting the extent of their differentiation may be a mechanism steer the bone response between maintenance remodeling and adaptive modeling regimes. Understanding how pharmaceutical treatments and mechanical loading work through these regimes, augment intrinsic sensing mechanisms, or tilt local signals to favor one or the other may provide valuable insight into optimizing or combining current treatments, and potentially suggest new therapeutic avenues. We first establish a method for quantifying modeling and remodeling in vivo using image registration on weekly micro-computed tomography scans. This technique is implemented in a study to assess the independent and combined effects of daily mechanical loading and parathyroid hormone injections in mice. We found that both resulted in significant increases in bone formation through anabolic modeling and remodeling, and while the modeling effects were usually additive or independent, the remodeling response was synergistic. Additionally, while PTH tended to exert its influence indiscriminately, the loading response was more targeted and pronounced in ways that mirrored local mechanical strains. Interestingly, this held true for catabolic modeling as well, where we observed a previously unreported phenomenon of load-induced increases in catabolic modeling in areas of low strain on the endosteal surface of cortical bone. We then began targeted interventions into the hematopoietic lineage cells, starting at their most terminally differentiated state in bone, the osteoclast. Using an injectable osteoclast maturation inhibitor, osteoprotegerin (OPG), we observed how arresting this process influenced modeling and remodeling in response to loading in normal mice, and in mice genetically modified to reduce sclerostin expression. We observed the expected reductions in catabolic modeling regardless of genotype. We also found that in sclerostin-depleted mice treated with OPG, anabolic modeling was elevated, and there was no added benefit of mechanical loading to the response in trabecular and endosteal compartments, suggesting the controlled manipulation of these factors can fully recapitulate the intrinsic mechanosensing capabilities. Since the loading response is largely modeling-based, these findings support the hypothetical determinant of the modeling/remodeling response being the preosteoclast/osteoclast ratio in these areas. In contrast, however, on the periosteal surface a pronounced load-induced anabolic modeling response persisted in all treatment conditions, suggesting the unique cell populations in the periosteum may have more robust, more finely tuned, or differentially regulated mechanosensing mechanisms. Finally, to probe the hematopoietic lineage further upstream and address the other side of the preosteoclast/osteoclast hypothesis, we utilized a novel genetically modified mouse model that allows for inducible macrophage (preosteoclast) ablation. Modeling and remodeling dynamics in response to loading were quantified in mice with normal or depleted macrophage quantities with concurrent normal or genetically-reduced sclerostin expression. In agreement with our hypothesis linking these cells to the anabolic modeling response, macrophage ablation resulted in significantly less anabolic modeling on trabecular and endosteal surfaces, which was not recovered by mechanical loading in either wild type or sclerostin deficient mice. Again, however, the periosteal surface was unique. Macrophage ablation did not reduce anabolic modeling on the periosteal surface, and loading still significantly increased it, regardless of sclerostin expression. Thus, similar to our findings with osteoprotegerin, a unique contrast existed between macrophage/preosteoclast ablation drastically reducing anabolic modeling and nullifying any mechanoresponse on trabecular and endosteal surfaces, but not the periosteal surface. Taken together, these studies outline and implement a novel method to quantify modeling and remodeling in response to loading and clinically relevant treatments, with an emphasis on perturbations of the hematopoietic lineage. Concurrent stimuli are used to observe and quantify overlaps and augmentations in treatment efficacies, with a focus on mechanisms related to mechanoadaptation. Future work will focus on targeted approaches to identify unique mechanosensing factors driving the periosteal response, more sophisticated data analysis tools to observe to what extent localized bone metabolism can be predicted by strain and morphology, and the protein and cellular-level dynamics that underlie our findings. As an addendum, a novel bone morphological parameter is described. A trabecular-cortical interface surface area metric (iSAM) is quantified on a set of cadaver bone segments from clinical high-resolution peripheral quantitative computed-tomography scans (a clinical analog to micro-computed tomography). iSAM is shown to correlate with stiffness and ultimate force derived from mechanical testing of the same samples, and improve correlations gleaned from traditional morphometric parameters alone.

Indiana University-Purdue University Indianapolis (IUPUI) / This investigation examined the relationships among light cured glass ionomer liner, light cured glass ionomer base, and composite resin material in the reattachment of fractured anterior tooth fragments. Seventy-five bovine incisor teeth were fractured and luted back together with three different materials (Universal Bonding Agent/TPH Composite Resin; VariGlass VLC Liner; VariGlass VLC Base, LD Caulk Div Dentsply Int Inc, Milford, DE) of equal number. The reattached fragments were subjected to thermocycling with a 40° C differential and then were loaded until the force required to detach the fragment was reached. The mean dislodgment strengths were 36.8 (± 25.6)kg for the composite resin, 36.4 (± 26.7)kg for the glass ionomer base, and 31.4 (± 29.S)kg for the glass ionomer liner. Analysis of variance demonstrated no significant difference between the three groups at p≤0.05. Also examined was the type of fracture after reattachment. Of the sixty-five teeth that were studied microscopically, 84.6 percent of the fractures were cohesive in nature, thus a breakdown occurred within the material itself.

No description available.

Igneous and metamorphic rock units have long been considered marginal aquifers yet they are a significant source for potable drinking water in many areas worldwide. Additionally, use of these systems is on the rise due to many factors including, contamination and overuse of surficial systems, as well as expanding population and drought. The Nashoba Terrane is a fault-bounded block of high-grade, steeply dipping metavolcanic and metasedimentary rock located in eastern Massachusetts, U.S.A. The Nashoba is northeast trending, extending from Oxford, MA to the Gulf of Maine south of Newburyport, MA. Seventeen previously drilled wells throughout the Nashoba were selected for use in this study. The goal of this study was to characterize the hydrogeologic system of the Nashoba Terrane. Wells studied were in three bedrock types: granite, schist and amphibolite. Three fracture types were identified: FPF, subhorizontal unloading joints and tectonic joints. Several major fracture orientation sets were also identified including northeast trending FPF, east-west trending and north-south trending tectonic joints as well as northwest trending tectonic joints. Dominant sets varied in the three rock types and the frequency of fractures was found to decrease with depth. Only four percent of all fractures measured in this study were flowing. Approximately 32% of the flowing fractures were northeast trending, 17% of subhorizontal fractures were flowing and the remaining 51% were of variable orientation and dip. In general, the orientation of fractures was not found to determine whether a fracture flows, nor was rock type a significant determinant of flow. There was no flow identified below 170 meters and the majority of flow in the Nashoba Terrane is constrained to the upper 100 meters. This is most likely due to decreased fracture frequency and permeability with depth. This study is significant to the search for a sustainable groundwater source in bedrock because results show that the few fractures are actually contributing to flow and that flow is primarily occurring near the surface.

Objectives The Radiographic Union Score for Tibia (RUST) scoring system has been validated in multiple studies assessing the healing of tibial fractures. Our objective was to assess the inter and intraobserver reliability for the RUST in diaphyseal femoral fractures treated with intramedullary (IM) nailing. Patients and Methods A total of 60 sets of anteroposterior (AP) and lateral radiographs of diaphyseal femoral fractures treated by reamed IM nailing were randomly selected from a prospectively collected database. The 60 sets of radiographs were then scored by three reviewers using the RUST system. Interobserver reliability was measured at initial scoring. The 60 sets of radiographs were scored again by the three reviewers to calculate the intraobserver reliability. Results The RUST scores ranged from 4 to 12 with a mean score of 11.3 ± 1.3. The interobserver intraclass correlation coefficient (ICC) was 0.87 (95% CI, 0.81-0.92) and the intraobserver ICC was 0.91 (95% CI, 0.88-0.94), which indicated excellent agreement. Conclusion This study demonstrated that the RUST system can be used reliably in the assessment of healing in diaphyseal femur fractures treated by reamed intramedullary nailing, with excellent interobserver and intraobserver reliability.

This thesis presents an application of a numerical formulation incorporating the effects of joints, cracks, and fractures to a soil subsidence predictions problem, and the extension of that formulation to combined discrete slip planes and jointed media continua formulations. The results obtained are compared to each other and to a physical centrifuge simulation performed previously on the same problem.

Introduction Chronic liver disease (CLD) causes more than 1 million deaths every year and remains a pandemic in the last decade affecting more than 600,000 patients in the United States. Previous studies found patients with CLD had increased risk of osteoporosis, so fractures were inferred to be complications of this condition. The aim of this meta-analysis is to summarize the best evidence that correlates CLD patients and the risk to develop osteoporotic fractures versus control patients without CLD. Methods A review of the literature using MEDLINE and EMBASE database was performed during December 2017. We included cross-sectional and cohort studies that reported relative risks (RR), odds ratios (OR) and hazard ratios (HR) comparing the risk of developing osteoporotic fractures among patients with CLD versus patients without CLD. Pooled OR and 95% confidence interval (CI) were calculated using generic inverse- variance method. The Newcastle-Ottawa scale was used to determine the quality of the studies. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results After the review of the literature, seven studies fulfilled the eligibility criteria established during the analysis. Significant association was found between CLD and osteoporotic fractures with a pooled OR of 2.13 (95% CI, 1.79 - 2.52). High heterogeneity among the studies was found (I2=88.5). No publication bias was found using Egger regression test (p=0.44). Conclusion We found a significant association between CLD and the risk of developing osteoporotic fractures. The calculated risk was 2.13 times higher for patients with CLD when compared with controls. The results showed high heterogeneity but no publication bias. More prospective studies are needed to fully understand the mechanisms involved in loss of bone density and osteoporotic fractures in order to improve the morbidity associated with this disease.

Background. There are roughly 300,000 rib fractures treated for in the United States each year. These represent 10-26% of thoracic trauma injuries and have about a 10% mortality rate. There is a common belief that mortality in rib fracture patients can be contributed to the diagnosis of pneumonia, but this study does not support that claim. Purpose. To determine the predictors of morbidity and mortality in rib fracture patients. Methods. Using a level 1 trauma center patient registry, we retrospectively analyzed all patients that were admitted with at least one rib fracture (n=1,344). All predictors were analyzed with linear regressions. Results. The average age of the patients was 55.48 ± 20.29 years old and ranged between 15 and 98. ISS (OR: 1.0508, p<0.001), bilateral fractures (OR: 1.9495, p = 0.009) and pulmonary contusion (OR: 1.7481, p = 0.022) were all significant predictors of pneumonia. The age of the patient (OR: 1.0467, p < 0.001), ISS (OR: 1.0585, p <0.001), having 6 or more fractured ribs (OR: 3.1450, p < 0.001), the presence of hemothorax (OR: 2.5063, p = 0.048), and the use of mechanical ventilation (OR: 13.2125, p < 0.001) were all significant predictors of mortality. Flail segments (OR: 1.9871, p = 0.067), ISS (OR: 1.1267, p < 0.001), pulmonary contusions (OR: 1.5329, p = 0.047), pneumothorax (OR: 1.4372, p =0.073) and pneumonia (OR: 21.4516, p < 0.001) are all predictors of requiring mechanical ventilation. Conclusion. There are many studies that indicate rib fracture patients who are diagnosed with pneumonia have a higher risk or mortality. With this in mind, the logical course of treatment would be to counteract the complications pneumonia brings as to reduce the risk or mortality. To do this, it is recommend the patient be put on mechanical ventilation. While this has been seen to help with pneumonia patients, this study provides evidence that health care professionals should look for ways to reduce the need for mechanical ventilation instead of using it to combat the pneumonia.

<p>An improved understanding of colloid transport in fractured media is required to assess the potential for microorganisms to contaminate groundwater, to develop groundwater management/protection plans, to design remedial action strategies based on the application of microorganisms, and to quantify colloid-facilitated transport of many organic and inorganic contaminants. Although colloid transport has been investigated to an extent in porous media environments, this field is still in its infancy in fractured media environments.</p> <p>Colloid transport in fractured media involves a host of complex and interacting processes, including (among others): advection, hydrodynamic dispersion, attachment and detachment, straining, size/ charge exclusion, and gravitational settling. These processes are, in turn, influenced by the physicochemical properties of fractured media, the geochemical properties of groundwater, hydrodynamics, and the colloid properties. This research program focused on investigating the effects of aperture field variability, specific discharge, and ionic strength on colloid transport in saturated, variable-aperture, single fractures. An extensive literature review was first conducted, and a combination of physical model experiments and numerical simulations were then employed to achieve this goal.</p> <p> Three transparent fracture replicas were fabricated, and the light transmission method was employed to obtain a direct measurement of each of the three aperture fields. A systematic series of hydraulic and tracer tests was conducted on each of the three experimental fractures, and the cubic law, mass balance and frictional loss apertures were calculated. Additionally, the experimental breakthrough curves were fit to the one-dimensional advection-dispersion equation. The results clearly demonstrate that the mass balance aperture is the only appropriate 'equivalent aperture' for describing transport in a single variable-aperture fracture, and that the mass balance aperture is an excellent approximation ofthe arithmetic mean aperture.</p> <p>A 3^3 factorial experimental design was then implemented to numerically investigate the interactive effect of the arithmetic mean (μb), standard deviation (σb), and anisotropic ratio (AR=λ^b x/ λ^b,y where λ^b x and λ^b y is the correlation length of the aperture field along x- and y- direction respectively) of single fracture apertures on dispersion regimes (specifically Taylor dispersion and geometric dispersion) and dispersivity. The simulation results show that: (1) for a fixed hydraulic gradient: (a) the dominant dispersion regime is controlled by μb, and to a lesser degree, σb, and (b) geometric dispersion becomes more dominant as the coefficient of variation (CoV = σb/μb) increases; (2) for a fixed mean aperture, the dispersivity and the spread in dispersivity for varying ARs increase with the CoV; and (3) the AR has a significant effect on dispersivity only when the CoV is large (>0.2).</p> <p> Numerical simulations investigating colloid and solute transport in single parallel-plate fractures, conducted using the Random Walk Particle Tracking (RWPT) method, demonstrated that: 1) There exists a threshold value, δo , of the aspect ratio, δ (δ= 2rc/b, where rc and b represent the colloid radius and fracture aperture respectively), where the average transport velocities of colloids and solutes are similar. When δ> δo , the Taylor Aris assumption is satisfied, and tp (tp = tc/ts, where tc and ts represent colloid and solute retention times respectively) decreases as δ increases, as is well documented in the hydrodynamic chromatography literature. However, when δ < δo , the Taylor-Aris assumption is violated, and tp increases as δ increases. This has never been documented before, and it helps to explain some seemingly contradictory work in the literature. 2) The Taylor dispersion coefficient and its extension by James and Chrysikopoulos (2003) will overestimate the colloid dispersion coefficient significantly when the Taylor-Aris assumption is violated. Additionally, these simulations demonstrated that tp and DL,coll/DL,solute (where DL,coll and DL,solute represent the dispersion coefficients of colloids and solutes respectively) decrease with increasing CoV, and that the anisotropy ratio, AR, only plays a minor role on these two ratios compared to the CoV. These observations have never been documented before to the knowledge of these authors, and have important implications towards the interpretation of colloid transport in both porous and fractured media.</p> <p> A combination of physical experiments, numerical simulations and visualization techniques was employed to investigate the impact of aperture variability, specific discharge, and ionic strength on colloid transport processes. The mean colloid transport velocity and colloid dispersion coefficient were obtained by fitting the analytical solution of the one-dimensional advection-dispersion equation (ADE) to the measured breakthrough curves. Two significant observations were made from the colloid transport experiment images: (1) colloids migrate along preferential pathways, and bypass some aperture regions; and (2) the colloid plume is irregular in shape, and becomes more irregular with increasing specific discharge, indicating non-Fickian transport. It is therefore postulated that the dispersivity cannot be completely determined by the aperture field characteristics alone; it is also a function of specific discharge. The colloid recovery in all fractures was found to increase with increasing specific discharge. For each specific discharge, it was found that the colloid recoveries in F2 and F3 were similar, and were always larger than the recovery in F1. This is consistent with the fact that the arithmetic mean apertures of F2 and F3 were similar (μb,F2= 1.57 mm, /μb,F3= 1.75 mm), and larger than that of F1 (μb,F1 = 0.88 mm). This suggests that it is the transport step (the step in which the colloids are transported from the bulk fluid to the vicinity of the fracture wall), and not the attachment step, that plays the dominant role in the colloid sorption process. It was also found that the mean transport velocity and dispersion coefficient of colloids are larger than those of solutes in F3 (CoV = 0.29), but similar to those of solutes in F1 (CoV = 0.78) and F2 (CoV = 0.71). This confirms the numerical simulation results from this work indicating that tp and DL,coll/DL,solute decrease with increasing CoV. These findings have significant implications on the interpretation of colloid transport data.</p> / Thesis / Doctor of Philosophy (PhD)