MS, Kent State University, 2016, College of Education, Health and Human Services / School of Health Sciences

PATEL, KRISHNA D., M.S., December 2016 Nutrition KNOWLEDGE, PERCEPTION, AND RISK REDUCING BEHAVIORS OF FEMALE COLLEGE STUDENTS WITH FAMILY HISTORY OF OSTEOPOROSIS (197 pp) Director of Thesis: Eun-Jeong (Angie) Ha, Ph.D. Family history of osteoporosis (FHO) has been recognized as one of the most important risk factors for osteoporosis development (Iqbal, 2000). The amount of bony tissue present at the end of skeletal maturation, known as peak bone mass, has been identified as a crucial component for osteoporosis prevention (Rizzoli, & Bonjour, 1999; Valimaki et al., 1994). The primary objective of this study was to assess knowledge and perception about osteoporosis and risk reducing behaviors of female college students with family history of osteoporosis in comparison with those without FHO. The secondary purpose of this study was to compare modifiable risk factors between the two groups. Inclusion criteria was limited to female college students enrolled at Kent State University in spring 2016 semester ages 18 and older. Family history was determined by self-reported data from participants indicating a FHO or fragility fractures in first- or second-degree relatives. Analysis of the data revealed that 95 students had FHO, making up 16.4% of the sample. Results showed there were significant differences in general knowledge and modifiable risk factors of osteoporosis, and risk perception between female college students with FHO and female college students without FHO (P=0.05). However, no significant differences in perception in risk reducing behaviors and modifiable risk factors were noted between the two groups (P=0.05). Future studies with a more consistent method of recording calcium intake and including calcium/vitamin supplementation questions are needed to reconfirm the findings of this study.

Committee: Eun-Jeong (Angie) Ha (Advisor); Natalie Caine-Bish (Committee Member); Karen Gordon (Committee Member) Subjects: Health Sciences; Nutrition

Master of Science, The Ohio State University, 2008, Graduate School

Committee: Not Provided (Other) Subjects:

Doctor of Philosophy in Engineering, Cleveland State University, 2022, Washkewicz College of Engineering

In healthy osteonal bone, embedded osteocytes form an intercellular communication network through overlapping cell membrane extensions, possibly defining an overlooked and clinically relevant lipid-mediated transport pathway for non-polar molecules. Previous techniques evaluating solute transport in cortical bone limit tissue analysis to microscale areas (less than 1 mm2) using tracers and assumptions that diminish clinical relevance, presenting the need for an improved method to evaluate solute diffusion in macroscale areas (greater than 1 mm2) of osteonal bone. A new diffusion system - constructed of glass and polytetrafluoroethylene - was designed and validated for this purpose, exhibiting minimal adsorption of solutes and resistance to leaking. A detailed protocol was also developed and validated for delipidizing experimental bone specimens. We measured the partition coefficient and effective diffusivity of 3H-estradiol and 14C-sucrose (polar control) through macroscale osteonal bone areas in native and delipidized tissue states, at physiological estradiol concentrations (sub-nanomolar). Delipidization resulted in a 30% reduction in the estradiol partition coefficient (n=6, p=0.028) and a 280% increase in the sucrose partition coefficient (n=6, p=0.0003). Likewise, delipidization resulted in a 69% decrease of the effective diffusivity of estradiol (1.02 x 10-8 cm2/s versus 3.18 x 10-9 cm2/s, n=18, p=0.007), while increasing the effective diffusivity of sucrose by 346% (n=19, p=0.047). The data reveal an unrecognized lipophilic transport medium in osteonal bone.

Committee: Joanne Belovich (Advisor); Ronald Midura (Advisor); Lutful Khan (Committee Member); Antonie van den Bogert (Committee Member); Xue-Long Sun (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Chemical Engineering; Chemistry; Engineering

MS, University of Cincinnati, 2021, Medicine: Biostatistics (Environmental Health)

Bone damping is a non-invasive measure of bone fragility and is identified as a better predictor of osteoporosis (OP) related bone fracture/fragility than bone mineral density (BMD). Subject with higher damping value demonstrates a heightened resistance to fracture. The purpose of this study was to identify the predictors of bone shock absorption (BSA) capacity measured as a damping factor by using model selection and multivariate multiple regression (MMR) method as well as regression tree. The main dataset was from an existing Cincinnati Lead Study (CLS) cohort. It is a prospective and longitudinal study examined early and late effects of childhood lead exposure on growth and development. The results of this study indicated that cortical vBMD, cortical thickness, endosteal circumference, cortical section modulus, current weight, and the number of pregnancies carried until the 3rd trimester were significant predictors of bone damping factor based on the method of model selection and MMR. Among the predictors with top nine highest variable importance values in regression tree method, four are the same as significant predictors from MMR analysis. Those are current weight, cortical section modulus, cortical vBMD, and endosteal circumference. Cortical section modulus and cortical vBMD have positive relationship with damping factor; however weight and endosteal circumference have negative relationship with damping factor. All variables' relationships with damping factor are clinically significant. Lack of dataset from normal people to compare the differences and the missingness of the data are the limitation of the study. Current weight, cortical section modulus, cortical vBMD, and endosteal circumference are significant predictor of damping factor based on the study results. They are biologically relevant to damping and statistically significant in the damping model.

Committee: Amit Bhattacharya (Committee Member); Marepalli Rao Ph.D. (Committee Chair) Subjects: Biostatistics

Master of Science, Miami University, 2020, Mechanical and Manufacturing Engineering

Vibration based monitoring techniques are widely used to detect damage, monitor the growth of inherent defects, system identification, and material parameter estimation for various engineering applications. These techniques present a non-invasive and relatively inexpensive tool for various biomedical applications, for example, in characterizing the mechanical properties of the bone and muscles of humans as well as animals. In recent years, it has been shown that fundamental natural frequencies and corresponding damping ratios can be correlated to the bone health quality indicators as associated with osteoporosis, osteoarthritis etc. In this research, through the investigation of clinical data, an analysis procedure is developed to investigate the correlation between the damping properties associated with both lower and higher modes of vibration and bone health quality. Subsequently, a data-driven system identification tool for reconstructing the parameters (mass, stiffness, damping distributions) in a low-dimensional human model is developed which utilizes selected measurements from the clinical study. It is anticipated that the analysis process and parameter identification techniques presented here can be developed and tuned for any individual human model and can be can be used as osteological monitoring tool for predicting early diagnostics pre-cursors of the bone or muscle related conditions or diseases.

Committee: Kumar Singh (Advisor); James Chagdes (Committee Member); Mark Walsh (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Mechanical Engineering; Osteopathic Medicine

MS, University of Cincinnati, 2020, Medicine: Clinical and Translational Research

Background: Osteoporosis and vertebral fractures are common in patients with Duchenne Muscular Dystrophy (DMD) treated with glucocorticoids. Bisphosphonates (BP) have been used in pediatric patients for treatment of osteoporosis. However, the long-term effects of oral BP therapy on vertebral morphometry and fractures in patients with DMD and glucocorticoid-induced osteoporosis are not known. Methods: We retrospectively studied patients with DMD who had been treated with oral BP for glucocorticoid-induced osteoporosis at a tertiary-care pediatric center between 2010 and 2017. Demographic data, and glucocorticoid and oral BP treatment histories were obtained from electronic medical records. Treatment outcomes were changes in lumbar (L1-L4) vertebral morphometry and fractures, as assessed by the Genant semi-quantitative method. Patients were included if they had both baseline, within 6 months prior to start of oral BP treatment, and at least one follow-up spine radiograph available for review. The primary outcome was the prevalence of vertebral fractures and the secondary outcome was change in Genant grading during treatment. Results: Fifty-eight patients with DMD (median age 12.2 years, range 5.5-19.6 years) were treated with glucocorticoids for a median duration of 4.7 years (range 1.3-12.6 years) and 33% were non-ambulatory at BP start. Vertebral fractures, defined by Genant grading =1, were present in 6-19% of L1-L4 vertebrae at baseline. Among patients who had radiographs at baseline and 1 year-post BP start, the prevalence of L1-L4 vertebral fractures remained stable post treatment (n=43; 5-18% at baseline vs 8-18% at 1 year, p value 1.00). The prevalence of vertebral fractures at each year up to 5 years was also not statistically different from that of baseline (p-value 0.08-1.00). Among patients who had serial radiographs for comparison, longitudinal examination showed no change in Genant grading in the majority of vertebrae (64-80%) up (open full item for complete abstract)

Committee: Patrick Ryan Ph.D. (Committee Chair); Jane Khoury Ph.D. (Committee Member); Meilan Rutter (Committee Member) Subjects: Surgery

Master of Science (M.S.), University of Dayton, 2019, Electrical Engineering

The purpose of this thesis was to develop an artificial intelligence algorithm to classify patient specific bone density from DICOM images acquired from orthodontic radiographic scans and to develop an osteoporosis screening tool. Osteoporosis is a degenerative disease that results in weakened, brittle bones; unfortunately, this disease presents no outward symptoms until a bone is fractured. The goal of this research was to develop a method to assist in the early diagnosis of this disease using routine dental and orthodontic scans. Bone density in this thesis was approximated by pixel intensities from patient DICOM images. Individual cephalometric patient scans from an orthodontist were read into a custom MATLAB algorithm, which extracted points from the patient's alveolar bone and determined the pixel intensity as an indicator for bone density. The alveolar (anterior mandible) bone was analyzed due to a correlation between tooth loss and osteoporosis documented in the literature. The intensity values of these pixels were averaged together as one global value for each patient. By comparing these global values versus age for 32 patients, a correlation between patient age and bone density was evident: as patients increase in age past 35 years, their bone density decreases, with different trend characteristics for men versus women. The results of this thesis provide a basis for the creation of a commercialized graphical user interface to aid medical professionals in the early detection of decreasing bone density in their patients.

Committee: Amy Neidhard-Doll Ph.D. (Committee Chair); Guru Subramanyam Ph.D. (Committee Member); Bradley Ratliff Ph.D. (Committee Member); Raj Kulkarni D.M.D. (Committee Member) Subjects: Biomedical Engineering; Electrical Engineering; Engineering

PHD, Kent State University, 2019, College of Nursing

Despite what is known about risk factors, preventive treatment, and increased prevalence of fragility fractures in post-bariatric surgical patients, little is known about how patient views of osteoporosis inform their commitment to bone health. The purpose of this research was to examine the lived experience of osteoporosis risk in people who have had bariatric surgery. The specific aims were to understand: 1. What it means to live with the risk of osteoporosis after bariatric surgery 2. The perceptions of osteoporosis risks postoperatively. This study used interpretive phenomenology to explore osteoporosis from the perspective of bariatric surgery patients. Purposive and snowball sampling was used to recruit individuals at risk for osteoporosis and a history of bariatric surgery. Eligibility criteria required participants to be female, over the age of 18 and understand and speak English. The study consisted of in-depth semi-structured interviews with 14 participants. Using open-ended questions, the interviews were audio recorded and transcribed. Study aims were addressed using strategies outlined by Diekelmann, Allen, & Tanner (1989). Findings are described under the relational theme of Looking out for Self, and supported by three subthemes Understanding, Protecting, and Preventing. This research provided an understanding of the risk of osteoporosis from the constructed realities and experiences of those who had bariatric surgery. Osteoporosis risk after bariatric surgery was not well known by participants. Furthermore, participants did not understand that vitamin deficiency can lead to osteoporosis. Participants perceived little to no risk of osteoporosis. Patients need to be aware of the risks of bariatric surgery; without this understanding of awareness about osteoporosis and risk of fracture, uncertainty will remain as to how to enhance osteoporosis prevention efforts in this population.

Committee: Denice Sheehan Ph.D. (Committee Chair); Christine Graor Ph.D. (Committee Member); Amy Petrinec Ph.D (Committee Member); Stacy Clare Ph.D. (Committee Member) Subjects: Nursing

Doctor of Philosophy (PhD), University of Toledo, 2019, Medicinal Chemistry

Osteoporosis is a chronic disease characterized by decreasing bone mineral density and integrity, leading to an increased risk of bone fracture. In the United States, more than half of the population over 50 years old is affected by low bone mass or osteoporosis. The progression of age-related osteoporosis has been shown to correlate with reduced bone marrow mesenchymal stem cell (MSC) differentiation to osteoblasts and increased MSC differentiation to adipocytes. Current pharmacological therapies act during the bone remodeling process by either enabling the osteoblast through an anabolic process or by an antiresorption action when inhibiting the osteoclast. Shown herein, synthesized PPARδ agonists exhibit the ability to control MSC differentiation in vitro by encouraging osteogenesis. This action offers a possible novel route for treating osteoporosis while simultaneously presenting a novel use for peroxisome proliferator-activated receptor δ (PPARδ) agonists, a receptor with currently no marketed selective drug and few selective agonists. The lack of known PPARδ agonists limited our ability to determine what potential PPARδ has for directing osteogenesis and possibly treating osteoporosis and other bone-related diseases. Therefore, we first synthesized additional PPARδ agonists as probes to explore the structure-activity relationships (SAR) of the receptor with regard to inducing osteogenesis in MSCs. The PPARδ agonists synthesized mimic the scaffold of the experimental PPARδ agonist, GW0742, developed by GlaxoSmithKline. The analogs were designed to conserve the pharmacologically important carboxylic acid along with the overall scaffold design containing a central heterocycle and terminal phenyl ring. Literature SAR indicated that the phenoxy acetic acid moiety used to display the carboxylic acid in GW0742, offered limited benefit over an E-cinnamic acid. Therefore, the latter was substituted in all analogs because it was more synthetically accessible and coul (open full item for complete abstract)

Committee: Paul Erhardt (Committee Chair); Peter Andreana (Committee Member); Jeffrey Sarver (Committee Member); Isaac Schiefer (Committee Member); L.M.V. Tillekeratne (Committee Member) Subjects: Biochemistry; Chemistry; Organic Chemistry

Doctor of Philosophy, The Ohio State University, 2019, Anthropology

Rather than resisting microscopic damage, human bone tissue is adapted to disperse energy through temporary plastic deformation, which it later repairs. Under low strains, bone cells continually turn over aging bone as a stochastic maintenance operation. Under high strains, stochastic remodeling is repressed, but microscopically damaged regions are resorbed and replaced through targeted remodeling. The triggering of bone remodeling by two opposing strain environments has long confounded attempts to link bone microstructure consistently to mechanical stimuli. Additionally, bone cells become uncoupled from mechanical control as they age, and begin eroding the cortex through more extensive and unrepaired bone resorption. Intracortical porosity is often treated as a consequence of aging, when it is accumulated enough to impact bone strength and fracture risk. Yet because cortical pores are produced by both stochastic and targeted remodeling activity, they are constantly forming in all strain environments and over the lifespan. This raises the question of whether pores in high-strain environments are morphologically “optimized” or resistant to the high risk of microcrack initiation and propagation in those regions. Moreover, does porosity increase fracture risk with age not only because it is increasing porosity, but because it is reshaping it morphologically? This study fundamentally asked whether the three-dimensional geometry of pore networks is morphologically optimized to resist local mechanical strain. The hypothesis of structure-strain pore morphotypes was tested in the human right-side femoral neck, a common site of osteoporotic fracture, and the human right-side midshaft fourth rib, a relatively unloaded control, for one male and one female per age decade from 20s to 80s. Extracted regions of each bone are visualized with high-resolution micro-CT imaging to reconstruct complete three-dimensional pore networks from 10 mm thick cross-sections of bone. These ima (open full item for complete abstract)

Committee: Samuel Stout (Advisor); Clark Larsen (Committee Member); Douglas Crews (Committee Member); Amanda Agnew (Committee Member) Subjects: Aging; Anatomy and Physiology; Biomechanics; Forensic Anthropology; Histology; Physical Anthropology

Bachelor of Science (BS), Ohio University, 2019, Biological Sciences

Bone is often regarded as a mostly inorganic tissue. Osteoporosis, a skeletal metabolic disorder characterized by increased bone fragility and fracture risk, is currently diagnosed by Dual X-Ray Absorptiometry (DXA) scan. However, DXA scanning is a poor predictor of fracture risk and bone quality, as it only assesses the mineral content of bone. Recent research increasingly suggests that other nonmineral parameters contribute to bone strength, such as size, geometry, and organic collagen. As a result, it is imperative to find a better diagnostic tool that more accurately encapsulates these other factors. One potential solution is Cortical Bone Mechanics Technology (CBMT), a novel technology being developed at Ohio University that uses noninvasive, radiation-free three point mechanical loading test to assess bone flexural rigidity (EI). Because CBMT is a mechanical test, it is believed to better detect changes in nonmineral factors. To assess this, compromising of the organic collagen matrix was induced using potassium hydroxide (KOH), which does not affect bone mineral. Paired cadaveric human forearms (n=16) were treated with either saline (n=8) or KOH (n=8). No statistically significant difference was present between the right and left T-scores of excised ulnas prior to chemical incubation (p= 0.40). No statistically significant difference between the KOH and saline cohorts prior to chemical incubation (p=0.27). Arms were assessed with DXA and CBMT both before and after treatment. Saline immersion did not reduce EIQMT (+0.9±1.2%, p= 0.76) or EICBMT (-0.6±2.3%, p=0.40). By contrast, KOH immersion reduced both EIQMT (-27.2±3.2%, p<0.0001) and EICBMT (-20.6±6.1%, p<0.01), with no difference between the magnitudes of these effects (p=0.21). Ulna BMD at the 1/3 region was not reduced by either saline (-1.4±0.9%, p = 0.09) or KOH (0.2±0.8%, p=0.76). Thus, CBMT detected collagen-mediated effects of KOH on the bending stiffness of whole cadaveric human ulna bones, and DXA (open full item for complete abstract)

Committee: Anne Loucks Ph.D (Advisor); Lyn Bowman Engr (Other) Subjects: Anatomy and Physiology; Biomechanics; Biomedical Research; Technology

Bachelor of Science (BS), Ohio University, 2019, Translational Health

Currently, there is no way to measure bone strength in living people. In the absence of such a measure, areal bone mineral density (aBMD) by dual energy x-ray absorptiometry (DXA) has become the standard used to assess bone health. DXA does not measure bone mechanics and aBMD does not predict fracture risk well. Cortical Bone Mechanics Technology (CBMT) is a device capable of measuring ulna bending stiffness in living people and has been shown to predict bone strength. Previously, Wynnyckyj and colleagues found 14 days of 1 M potassium hydroxide (KOH) treatment on the endocortical surface of emu tibias reduced elastic modulus values by 17% through bone collagen degradation. DXA measurements of aBMD did not change after KOH treatment. The purpose of this study was to determine the accuracy of CBMT in measuring excised human ulna flexural rigidity (EI) and estimating cortical bending strength with potassium hydroxide (KOH) induced collagen degradation by comparing measurements made by quasi-static mechanical testing (QMT). DXA measurements of the ulna were made to test DXA's ability to detect changes in the bone. An additional goal of this study was to compare periosteal (immersion) KOH treatment to the endosteal (endocortical) treatment used in the study performed by Wynnyckyj and colleagues. A randomized experimental design was used in which eight pairs of ulna bones excised from cadaveric human arms were immersed in 1 M potassium hydroxide (KOH) solution or a 0.9% calcium-buffered saline solution. For each pair of arms, the saline solution served as the control for the KOH solution. DXA measurement of ulna area (cm2), BMC (g) and aBMD (g/cm2) at the 1/3 region of the ulna and CBMT and QMT measurement of ulna EI (Nm2) were made before and after immersion. QMT measurements of bone bending strength are destructive and could only be made after immersion. The maximum moment (Mmax, Nm) was used to indicate bone strength. Effect of KOH on bone strength was detected by (open full item for complete abstract)

Committee: Anne B. Loucks PhD (Advisor) Subjects: Biomechanics; Health Sciences; Technology

Doctor of Philosophy, The Ohio State University, 2018, Biomedical Engineering

Osteoporosis is a common degenerative bone disease that results in bone loss and fracture in the elderly and to people of any age with disabilities. Current drug treatments only provide either increased bone formation or decreased bone resorption, and can cause adverse effects. As an alternative to drugs, low intensity vibration (LIV) may improve skeletal health without potential side effects from drugs. LIV has been shown to increase bone health short term in both animal and clinical studies. Long term benefits from LIV are currently unknown, so the objective of this research was to investigate the long-term effects of whole body vibration therapy on bone morphology, bone mineral density (BMD), mechanical properties, and histological bone formation. In this study, 10-week old female mice were given LIV for 8 weeks; while a control group received a SHAM treatment i.e. no vibration. Two sets of groups remained on study for an additional 8 or 16 weeks post treatment (N=17). Femoral dynamic loss stiffness (K”) significantly increased by 18% after 8-weeks of LIV compared to SHAM. Damping, tan delta, and loss stiffness, significantly increased by 18%, 16%, and 17% respectively at 8 weeks LIV compared to SHAM. Finite element models of applied LIV signal showed decreased stress in the mid- diaphyseal region at both 8-week LIV and 8-week post treatment compared to SHAM. Residual mechanical changes in bone during and post-LIV indicates that LIV could be used to increase mechanical integrity of bone. Epiphyseal trabecular mineralizing surface to bone surface ratio (MS/BS) and bone formation rate (BFR/BS) was significantly greater in the LIV group compared to the SHAM group at 8 weeks by 92% and 128% respectively. Mineral apposition rate (MAR) was significantly greater in the LIV group 16 weeks post treatment by 14%. In the metaphyseal trabecular region at 16 weeks post treatment, MS/BS and BFR/BS was significantly greater in the LIV group by 10 (open full item for complete abstract)

Committee: Richard Hart PhD (Advisor); Alan Litsky ScD (Committee Member); Do-Gyoon Kim PhD (Committee Member); Clark Larsen PhD (Committee Member) Subjects: Biomedical Engineering

Bachelor of Science (BS), Ohio University, 2017, Biological Sciences

Osteoporosis is a disease characterized by diminished bone strength, resulting in an increased risk for fracture with minimal trauma. Though osteoporotic fractures present severe consequences for patients and health communities alike, there remains to be an accurate diagnosis for this disease. There are many characteristics that influence bone strength, ranging from mechanical, microstructural, to geometrical in nature. This project specifically aimed to assess cortical porosity, diameter, and bending stiffness as predictors of bending strength in the human radius. Data was collected from thirty cadaveric human radii from men and women between the ages of 17-99 years. Bending strength and bending stiffness were measured by the gold standard three-point bending method, quasi-static mechanical testing (QMT). Interosseous diameter was measured from both higher resolution µCT and lower resolution CT scans. Finally, cortical porosity was measured from µCT scans in the NIH image-processing software ImageJ. These measurements were guided by 3D Avizo models. Simple linear regression analyses revealed that bending stiffness predicted bending strength with the least amount of uncertainty (SEE=3.2 Nm). Cortical porosity demonstrated the weakest relationship with bending strength (SEE=12.0 Nm). Predictions of bending strength by µCT diameter were not different from those made by CT diameter (p=0.37). In comparisons of cortical porosity in the radius and ulna as imaged from the same arms, porosity at the 55%L of the ulna was the only unbiased predictor of radius porosity adjacent to the QMT fracture site (p=0.12). Thus, at the midshaft, cortical porosity of the ulna and radius appear to be indistinguishable.

Committee: Anne B Loucks PhD (Advisor) Subjects: Anatomy and Physiology; Biology; Cellular Biology; Endocrinology; Kinesiology; Medical Imaging; Molecular Biology; Morphology; Physiology

Bachelor of Sciences, Ohio University, 2017, Biological Sciences

Osteoporosis is a systemic, skeletal disease characterized by decreased bone strength that predisposes individuals to an increased risk of fracture. Unfortunately, there is no clinical device able to measure bone strength. Instead, osteoporosis is diagnosed on the basis of bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA). However, research has shown that BMD does not predict fractures well. Bone strength has been shown to be predicted accurately by bone stiffness (EI), but no clinical device measures bone stiffness either. Ohio University is developing Mechanical Response Tissue Analysis (MRTA) to measure EI of the human ulna in vivo. Accurate predictions of ulna bending strength are of limited clinical importance, however, unless the ulna is representative of other long bones. The radius is of further clinical importance because a fracture of the radius often precedes and could predict fractures at more serious sites such as the hip. This project used cadaveric radius specimens, of which the ipsilateral ulna was previously tested, to determine the accuracy with which radius bending strength was predicted by various predictors from both mechanical testing of the radius and ulna and DXA measurements of the radius. Mechanical testing methods included MRTA of the ulna in vivo and quasistatic mechanical testing (QMT) of the ulna and radius ex vivo. DXA measurements included scans of the standard UD and 1/3 sites of the radius. Linear regression analyses revealed that ulna EI measured by MRTA is a more accurate predictor of radius bending strength than BMD measurements, but is not the most accurate predictor. Radius EI and BMC at the 1/3 site were the most accurate predictors of radius bending strength, though not significantly different from each other. The most accurate predictor of radius EI was BMC at the 1/3 site.

Committee: Anne Loucks Ph.D (Advisor); Lyn Bowman Engr (Other) Subjects: Anatomy and Physiology; Biomechanics; Medical Imaging

MS, Kent State University, 2016, College of Arts and Sciences / School of Biomedical Sciences

Trafficking Protein Particle Complex 9 (TRAPPC9) is a major subunit of TRAPP Complex. TRAPPC9 has been reported to bind IKappaB Kinase (IKK2) NF-KappaB-inducing kinase (NIK) where it plays a role in the canonical and non-canonical of NFkB signaling in Osteoclast (OC) differentiation and function. Respectively, the role of TRAPPC9 in protein trafficking in OC has not been studied. In this study, we first examined the co-localization of TRAPPC9 with cathapsin-K (Cathp.K), known to mediate OC resorption suggesting that TRAPPC9 mediates the trafficking and function of OCs. Second, to identify TRAPPC9 protein partners important for OC-mediated bone resorption, we conducted immunoprecipitation of TRAPPC9 isolated from terminally differentiated OCs followed by mass spectrometry analysis. Surprisingly, our data showed that TRAPPC9 binds various protein partners. One of those proteins is L-Plastin (LPL). LPL is localized at the podosomes and plays a crucial role in actin aggregation thereby actin ring formation and OC function. Recent studies reported that LPL null OCs demonstrated normal OC differentiation phenotype and peripheral podosomes aggregation. However, significant disruption in actin ring formation and the sealing zone region were observed. Although the role of LPL in OC-mediated bone resorption has not reported in details. Here, we investigated the potential regulatory role of TRAPPC9 and LPL-mediated OC differentiation and function. Thereby, we assessed the localization of TRAPPC9 and LPL in OC and found that TRAPPC9 is co-localized with LPL within the periphery of OC. Next, we determined the effect of TRAPPC9 overexpression using viral system on LPL recruitment to the actin ring. Interestingly, our data showed that TRAPPC9 overexpression promotes the recruitment of LPL to the actin ring when compared to controlled cultures. This recruitment is associated with increasing OC-mediated bone resorption. In conclusion, our hypothesis is that TRAPPC9 plays a regulator (open full item for complete abstract)

Committee: Fayez Safadi (Advisor) Subjects: Biomedical Research

Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2016, Biomedical Sciences (Orthopaedic Sciences)

Bone marrow adipose tissue (BMAT) is an endocrine organ and heterogenic adipose depot that is located throughout the body in the marrow of bones. BMAT has the potential to modulate bone microenvironment. Recent studies have found that it is region-specific and species specific under various metabolic pathophysiological conditions such as aging, caloric restriction, diabetes, and sex steroid deficiency. Previously, our lab concluded that BMAT has phenotypic characteristics of white adipose tissue (WAT), brown adipose tissue (BAT), and brown-like or beige adipose tissue. This project investigated whether sex steroids control the bone morphology and phenotype of bone marrow adipose tissue in male and female animals. Results indicate that there are significant differences in bone mass and fat deposition of the tibia of adult male and female mice. However, sexual dimorphism in the expression of those adipose tissue markers in the BMAT was not observed in the qRT-PCR analysis of the proximal tibia of OVX and ORX animals.

Committee: BEATA LECKA-CZERNIK (Advisor); MARTIN SKIE (Committee Chair); A CHAMPA JAYASURIYA (Committee Member); EDWIN SANCHEZ (Committee Member); JENNIFER HILL (Committee Member) Subjects: Biomedical Research; Endocrinology

MS, University of Cincinnati, 2016, Medicine: Clinical and Translational Research

Purpose: Fractures and poor bone health due to limited ambulation are significant concerns for patients with Spinal Muscular Atrophy (SMA). However, the prevalence of fractures, low areal bone mineral density (aBMD; Z-score ≤ -2.0) of the lateral distal femur (common fracture location in non-ambulatory children) and of osteoporosis by SMA subtype is not known. Methods: We reviewed data from SMA patients ages 12 months to 25 years, seen at a single institution between January 2005 and January 2015. Fracture history was reported at annual clinic visits. aBMD was obtained from dual energy x-ray absorptiometry scans of the lumbar spine, total body, and lateral distal femur. Results: Median age at initial SMA visit was 1.8 years, but differed by SMA subtype. DXA data were available on 69% of the sample: of these, 90% had a BMD Z-score ≤-2.0 SD at time of first DXA. aBMD Z-scores at all sites was lower with worsening SMA severity, decreasing over time at the lateral distal femur. Fractures occurred in 36% of patients with the femur being the most common location (25 of 53 total fractures). Median age at first fracture was significantly younger with worsening SMA severity. 13% of patients had multiple fractures. Only 8.5% of patients fulfilled criteria for osteoporosis. Conclusion: Low BMD is highly prevalent in SMA patients at the time of first DXA. Fracture frequency is also high with a predominance of femur fractures in all subtypes. However, few patients met ISCD diagnostic criteria for osteoporosis. Our data suggests poor bone health is a significant concern for SMA patients, but may be under-recognized using the 2013 International Society for Clinical Densitometry criteria for diagnosis of osteoporosis in children.

Committee: Erin Nicole Haynes Dr.P.H. (Committee Chair); Philippe F. Backeljauw M.D. (Committee Member); Heidi J. Kalkwarf Ph.D. (Committee Member); Jane Khoury M.S. Ph.D. (Committee Member) Subjects: Surgery

Master of Arts in Gerontology, Youngstown State University, 2015, Department of Sociology, Anthropology and Gerontology

Background: Hyperkyphosis is a spinal deformity causing an exaggerated anterior curvature of the thoracic spine. While the causes and consequences of hyperkyphosis are not well understood, hyperkyphosis may be associated with an increased risk for clinical consequences and other adverse health outcomes, such as functional limitations, musculoskeletal alterations, poor quality of life and mortality.Method: A retrospective study was conducted of 2500 patients at an Osteoporosis Clinic in northeast Georgia who sought initial treatment between January 2004 and March 2015 to evaluate the associations between spine curve measurements and functional motion associated with spine load, balance, strength, and flexibility during daily living tasks. Analyses conducted examined the associations between kyphosis and functional motion, as well as their associations with quality of life. These associations were assessed using the Pearson-product-moment correlational coefficient and Spearman's Rho.Results: The author of the article observed that degree of kyphosis was significantly associated with functional motion (r = -.274, p < .01) and kyphosis was also significantly associated with quality of life (r = -.071, p <. 01) Scores on functional movement were also associated with quality of life (r = .221, p< .01). Despite these findings, the strength of these correlations were small.Conclusions: While functional motion and kyphosis can impact quality of life, these associations may not be as strong as previously believed. This study calls for further exploration of the unique relationship of the multiple factors that can impact perceived quality of life, and a further analysis of confounding variables.

Committee: Dan Van Dussen PhD (Advisor); Amy Weaver PhD (Committee Member); Tiffany Hughes PhD (Committee Member) Subjects: Gerontology

Bachelor of Science (BS), Ohio University, 2015, Biological Sciences

Osteoporosis is a disease characterized by a decline in bone strength leading to an increased risk of fracture, but no clinical device measures bone strength. Bone strength is strongly associated with bone stiffness (EI), but no clinical device measures EI either. Mechanical Response Tissue Analysis (MRTA) is being developed to measure EI in human ulna bones in vivo. Bone EI depends strongly on bone interosseous diameter (ID), and cortical porosity (CP) has been proposed for assessing fracture risk. This project compared the accuracies with which ulna bending strength was predicted by CP, ID, and EI in 35 cadaveric arms from men and women ranging widely in age (17-99 yrs.) and BMI (13-40 kg/m2). ID was obtained by computed tomography (CT). Ulna EI was measured noninvasively by MRTA on intact arms, while EI and bending strength were measured on excised ulnas by the gold standard method, Quasistatic Mechanical Testing (QMT), which cannot be employed in vivo. ID and CP were obtained in fractured ulnas by micro-computed tomography (µCT) by ImageJ using Avizo® 3D models to locate the endosteum. Simple and forward stepwise multiple regressions revealed that CP was the least accurate predictor of bending strength (SEE≥235N). ID as more accurate (SEE≤163N, p=0.02). Accuracies of predictions by ID from CT and µCT images were indistinguishable (p=0.35). Accuracies of predictions by EI measured by QMT and MRTA (SEE≤91N) were more accurate than CP and ID alone or together (p≤0.02) and indistinguishable from one other (p=0.12). Age was the only predictor to explain any (1%) variance not explained by EI. No model with >2 predictors was significant.

Committee: Anne Loucks (Advisor); Lyn Bowman (Other) Subjects: Anatomy and Physiology; Biology; Biomechanics; Biomedical Engineering; Biomedical Research; Health; Scientific Imaging