Introduction: The Rho family of small GTPases, including Rac1 and Rac2, are key regulators of osteoclast differentiation and function; however, little is known about their roles in bone quality and aging. Methods: Male four and nine month old mice (n=10) with Rac1, Rac2 or both (DKO) isoforms deleted in osteoclast precursors were assessed using dual energy x-ray absorptiometry (DXA), scanning electron microscopy (SEM), micro computed tomography (microCT), compression, torsion and three-point bending testing, back scattered electron microscopy (BSE), Goldner’s trichrome and TRAP staining. Results: All Rac null mice demonstrated decreased cortical structural properties and improved trabecular architecture. With age, Rac null mice demonstrated the ability to attenuate age-related bone loss. Conclusions: Using an in vivo model with Rac1, Rac2 or both Rac isoforms deleted in osteoclasts, our findings demonstrate the deletion of Rac1 and Rac2 compromised cortical bone while improving trabecular bone properties and attenuated age-related bone loss.

Introduction: The Rho family of small GTPases, including Rac1 and Rac2, are key regulators of osteoclast differentiation and function; however, little is known about their roles in bone quality and aging. Methods: Male four and nine month old mice (n=10) with Rac1, Rac2 or both (DKO) isoforms deleted in osteoclast precursors were assessed using dual energy x-ray absorptiometry (DXA), scanning electron microscopy (SEM), micro computed tomography (microCT), compression, torsion and three-point bending testing, back scattered electron microscopy (BSE), Goldner’s trichrome and TRAP staining. Results: All Rac null mice demonstrated decreased cortical structural properties and improved trabecular architecture. With age, Rac null mice demonstrated the ability to attenuate age-related bone loss. Conclusions: Using an in vivo model with Rac1, Rac2 or both Rac isoforms deleted in osteoclasts, our findings demonstrate the deletion of Rac1 and Rac2 compromised cortical bone while improving trabecular bone properties and attenuated age-related bone loss.

Forty ovine femurs were harvested and allocated into four testing groups; Fast-Normal, Fast- Decalcified, Slow-Normal, Slow-Decalcified. Contralateral pairings were used within these groups for closer comparison. Dynamic testing apparatus was designed and built allowing rates of strain similar to road traffic accidents to be investigated. These strain rates were achieved by using a pneumatic actuator to apply the load. Slow rate loading was achieved by testing with a commercially available mechanical testing machine at a rate of strain similar to that created by walking. Bone quality was altered by ultrasonically assisted decalcification in EDTA. Levels of mineral dissolution equivalent to the loss of bone mineral density (BMD) of a 75 year old woman were targeted. Whole bone was used for these experiments to facilitate comparison with real fracture radiographs obtained from NHS database. Fracture patterns and degree of comminution were similar between experimental and patient data. Bone is often analysed as a simple beam (engineers bending theory). This method of stress analysis was compared with a method that recognised the change in cross section over the length of the bone. Accounting for this had a highly significant effect on the calculated flexural modulus (p<0.0005).The length to depth ratio of whole bone indicates that shear forces cannot be ignored. The effect of the contribution from shear force on the deflection was investigated. After accounting for deflections due to shear, calculated normal strains agreed with literature values. Deflection due to shear was found to make a significant contribution to the deflection The effect of storage (freezing) on the mechanical properties at high strain rate was evaluated: no significant differences were found for force and deflection at failure. The main body of testing gave the following results: Normal quality bone, rate compared showed significant differences for Ultimate Stress, Ultimate Strain, Yield Strain, Flexural Modulus and Toughness. Demineralising bone resulted in no statistically significant differences between the loading rates for the Stress at failure. Yield Strain, Ultimate Strain, Flexural Modulus and Toughness did show significant differences. The fast loading tests showed significant differences when comparing quality for Stress at failure but not at Yield. Significant differences were found when comparing toughness. Slow loading tests showed significant differences between bone qualities for Stress at failure in contralateral pairs. No significant differences were found for strain or toughness. These results indicate that bone of normal quality can withstand higher than normal stresses for short durations. This ability is lost in demineralised bone. The high loading rate tests revealed closely matched strains at failure for both bone qualities, lending support to the strain based failure theory for bone at traumatic strain rates.

Clinicians have described the success rates of dental implants. The use of implants is projected to increase in the future. With a 5-10% failure rate, it is unclear the exact factors that are associated with implant failures. To improve upon these success rates, it is critical to understand parameters associated with implant failure including: periodontitis, peri-implantitis, systemic diseases, site preparation, dental history of the implant site, bone quality, materials, occlusion, and treatment timelines. While bone quality is associated with failure, objective measures to assess bone quality and characteristics are scarce. Therefore, the aim of this study is to determine whether possible comorbidities, associated dental parameters, and measurable bone quality are possible predictors of implant failure. In this study, we utilized the electronic health record system axiUm® to retrospectively investigate non-failed (NF) and failed (F) dental implants from a patient cohort with 149 implants placed between 2012-2015 at Virginia Commonwealth University School of Dentistry. A chart review was conducted extracting information on age, gender, systemic diseases, smoking, occlusal trauma, parafunction, bone grafting history, treatment timelines, implant site/type/placement protocol, infection, torque at placement, bone quality and microarchitecture assessed by the novel, innovative technology: trabecular bone score (TBS). A total of 149 implants, 46 failures and 105 non-failed controls, were selected based on similar implant sites. Preliminary data obtained from analysis suggests that average time from implant placement to failure was 6.6 months (0.55 years). Parafunction habit (p=0.0202) and increased number of implants (p=0.0478) were found to be associated with increased implant failure.

For the modern dairy cow, advances in genetics and breeding for productivity has resulted in an increasing incidence of health disorders and reduced longevity. One of the most important health problems is lameness, which has led to significant economic, production and welfare consequences. A reduction in lameness will improve the economic future of the dairy industry through increased profitability and decreased welfare-related problems. Although positive attempts have been made by researchers and the industry towards improving lameness, it has remained a persistent ailment for dairy farmers. Further analysis of the genetic and environmental factors influencing lameness is warranted so that selection indices and management practices can be modified leading to improved health and welfare of the dairy cow. Several factors that cause dairy cow lameness have been implicated. I reviewed previous studies on these causative factors as well as the association between lameness, longevity and fertility. It has also been suggested that lameness affects milk production of dairy cows, but reports on the association between lameness and daily milk yield of cows have varied among researchers. Using locomotion score data on 248 cows from the Langhill herd, I investigated the relationship between locomotion score which has a high genetic correlation with lameness and various explanatory variables and also the association between daily milk yield and lameness. The study revealed that the most significant factors affecting locomotion are management regime (high concentrate feed and all year indoor housing; low concentrate feed and outdoors in summer) and time of year when cows are locomotion scored. It also showed that lameness adversely affects the milk yield of later lactation cows, and that high yielding cows are more susceptible to lameness. Housing environment plays a significant role in the health and welfare of dairy cows. With national type evaluation records, I estimated the association between housing systems and lameness-related type traits as well as genetic parameters for the locomotion traits. The analysis indicated that cows kept at pasture had favourable linear and composite type trait scores compared with cows in cubicles, straw yards and slatted floors or loafing yards. Locomotion score had strong genetic and phenotypic correlations with the leg and feet composite. Bone quality, which is a new trait in the UK type classification scheme, was moderately heritable (0.23) and had a moderate and positive genetic association with locomotion and leg and feet composite. This suggests that breeding for flatter, more refined bones could reduce locomotion disorders and help improve the longevity of the dairy cow. Analysis of national data again showed reduced incidence of digital dermatitis (DD) for cows at pasture and those with flatter, more refined bones, higher locomotion score and better leg and feet composite. Estimates of genetic parameters indicated heritable variation of DD among cows and moderate genetic associations between DD and production traits and longevity. Incorporating DD in future selection indices will be useful for increased productive life. Using random regression, I analysed changes in type traits associated with lameness (locomotion, rear legs, side view, foot angle and leg and feet composite) in relation to time (months) that cows had spent in cubicles before being classified. The general trend supported the fact that cubicle housing is unfavourable to these traits. There was significant evidence of a genotype x environment interaction, suggesting variation between bulls in the sensitivity of their daughters to cubicle housing with time.

Non-invasive estimates of bone quality are of great interest as they could potentially improve the diagnosis and treatments for bone disorders, such as osteoporosis, and could aid in preoperative planning of surgical interventions, improving patient outcomes in orthopaedic trauma. Quantitative computed tomography (QCT) is currently being investigated as a method of estimating structural bone mineral content (sBMC) and, thus, bone quality. However, the reported correlations between QCT and sBMC have been variable and the relationships reported between sBMC and the apparent elastic modulus (E*) of bone have been even more variable. A series of investigations are presented, relating QCT, sBMC, apparent density and the E* of bone. These studies were performed with the ultimate objective of determining the appropriateness of QCT as a predictor of the E* of bone and whether the E* of bone could be predicted from information regarding the sBMC and apparent density. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2008-01-31 22:00:08.77 / This work was funded by the Canadian Institutes of Health Research.

Two experiments were conducted to determine the effects of phosphorus (P) in growing pigs. In experiment 1, fifty-four pigs were randomly allotted to three diets with available phosphorus (aP) concentrations of 0.23%, 0.17% and 0.11%. In experiment 2, twenty-eight pigs were assigned to four treatments including T1 (diet with 0.23% aP for three wks), T2 (diet with 0.11% aP for wk1 replaced by diet with 0.23% aP for wk2 and wk3), T3 (diet with 0.11% aP for wk1 and wk2 replaced by diet with 0.23% aP for wk3) and T4 (diet with 0.11% aP for all three wks). The 0.11% aP diet proved to be very low with negative effects on performance and bone quality. Reduced dietary P resulted in reduced P intake and reduced P excretion. In conclusion, growing pigs are sensitive to P and environmental pollution because of dietary P can be reduced by dietary manipulation of P.

The osteoclasts, the bone cells responsible for bone degradation, have a crucial role in the age-related bone loss and post-menopause osteoporosis. Rac1 and Rac2, members of the Rho-family of small GTPases, are known for having a key role in osteoclast formation and activity, which could be translated to bone quality. In this study, we characterize the roles of Rac1 and Rac2 on bone quality using an aged and osteoporotic mouse model. Bones from wild type, Rac1KO and Rac2KO mice were harvested for mechanical tests, bone densitometry, micro-computed tomography and histomorphometric analyses to evaluate bone mineralization and architecture. We observed that the deletion of Rac1 or Rac2 in pre-osteoclasts minimized bone loss in both age-related and post-menopause osteoporosis. These results highlight the importance of the two small GTPases in bone remodeling and identify Rac1 and Rac2 as potential targets for the development of new therapies for the treatment of osteoporosis.

The osteoclasts, the bone cells responsible for bone degradation, have a crucial role in the age-related bone loss and post-menopause osteoporosis. Rac1 and Rac2, members of the Rho-family of small GTPases, are known for having a key role in osteoclast formation and activity, which could be translated to bone quality. In this study, we characterize the roles of Rac1 and Rac2 on bone quality using an aged and osteoporotic mouse model. Bones from wild type, Rac1KO and Rac2KO mice were harvested for mechanical tests, bone densitometry, micro-computed tomography and histomorphometric analyses to evaluate bone mineralization and architecture. We observed that the deletion of Rac1 or Rac2 in pre-osteoclasts minimized bone loss in both age-related and post-menopause osteoporosis. These results highlight the importance of the two small GTPases in bone remodeling and identify Rac1 and Rac2 as potential targets for the development of new therapies for the treatment of osteoporosis.

The tapping torque using in this thesis is used to test the quality of the jaw bone.Testing the quality of jaw bone is the first step of placing the implant. However,several existing methods for various reasons are not the best ways to measure thequality of bone quality. In this project, a solution explored in this pilot study wasbased on the fact that bone quality can be assessed from cutting resistance whentapping or threading in bone [Johansson P, Strid K-G. 1994], and the experimentwhich tapping into testing material has been done by Carlsson TL Medical AB.Authors’ duty is to analysis the data what we get from industrial supervisor tosummarize a formula to present the thickness of bone and createa scale connecting the tapping torque and material quality. Then compare thetapping torque of the known-quality material with the tapping torque of bone,quality of bone can be known. The study about measurement of bone thickness andscale connecting the cutting force with material quality describe the benefit thatdental implant surgery will more accurate than surgeon’s feeling and otherexpensive equipment according to the torque which is measured in pre-tappingprocess