Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Two trials compared the effects of canola meal (CM) and juncea meal (JM) with and without dietary enzyme supplementation, on production performance, egg quality, bone quality and liver health characteristics of white- (WSLH) and brown-shell egg laying hens (BSLH). A total of 360 Lohmann LSL-Lite White (Trial 1, WSLH) and 300 Lohmann Brown-Lite (Trial 2, BSLH) laying hens were fed one of 10 isoenergetic and isonitrogenous diets (Soybean meal, 10 % CM, 20 % CM, 10 % JM or 20 % JM with or without a dietary enzyme cocktail of Superzyme OM and Bio-PhytaseTM) for 48 weeks. Based on the results of production performance, incidence of mortality, egg quality, bone quality, and liver health data, up to 20 % CM or JM can be included in diets of WSLH and BSLH without detrimental effects. Enzyme should be included in diets for both WSLH and BSLH.

There is a pressing need for better assessment of bone strength as current clinical tools do not directly measure bone mechanical properties, but offer only surrogate measures of bone strength. We conducted an ex-vivo study of emu bones to examine how two investigative devices, hr-pQCT and MRTA, compare to current clinical tools (DXA and QUS) in predicting true bone mechanical properties. We found that hr-pQCT parameters were able to assess bone strength as well as DXA and better than QUS, while MRTA was able to predict bone strength well in low-density but not high-density bones. Our results suggest that both hr-pQCT, which has the unique ability to specifically assess the various determinants of bone strength, and MRTA, which measures a bone mechanical property (stiffness), have great potential for use as clinical tools that can assess various components of bone strength not measured by current devices.

Bone’s ability to resist fracture is often ignored until a low-energy fracture occurs. Patients with Chronic Kidney Disease (CKD) or osteoporosis are at an increased risk of low-energy fracture. Generally, fracture risk is evaluated by using a bone mineral density (BMD) test. BMD values; however, do not fully predict bone’s ability to resist fracture. This suggests that other parameters may be involved. Bone quality is the term used to describe these parameters, which are categorized into three groups: structural, material, and microdamage. The aim of this dissertation research was to examine whether bone quality was altered in patients who: 1) had abnormal bone turnover (high or low) due to CKD, 2) suffered a low-energy fracture despite normal BMD, or 3) had osteoporosis and were treated with bisphosphonates. These studies used iliac crest bone specimens from Caucasian females aged 21 to 87 years. Bone’s material parameters were measured by Fourier transform infrared spectroscopy. The key finding from the turnover study was that high and low turnover was associated with altered bone quality. Specifically, bone with high turnover had a lower mineral-to-matrix ratio compared to normal and low turnover (p<0.05), while low turnover had a lower cancellous bone volume and trabecular thickness compared to normal or high turnover (p<0.05). The key finding from the fracture study was that patients with normal BMD and low-energy fractures had altered bone quality (greater collagen crosslinking ratio) compared to patients who had low-BMD with low-energy fractures and healthy subjects (controls) (p<0.05). Lastly, the key findings from the bisphosphonate studies were that osteoporosis patients treated with these drugs had altered bone quality (specifically, greater (p<0.05) mineral-to-matrix ratio) compared to untreated turnover-matched osteoporotic patients, and that were several positive linear correlations with the nanoindentation derived Young’s modulus and hardness of cortical and trabecular bone and the duration of bisphosphonate treatment (p<0.05). The findings presented provide further evidence that bone quantity is not the sole factor in determining bone’s ability to resist fractures and that bone quality is an essential factor.

This study characterized the effects of two anti-diabetic drugs, a thiazolidinedione (TZD) and a Dipeptidyl Peptidase-4 (DPP-4) inhibitor on bone quality in a glucose intolerant mouse model. Bone quality in a DPP-4 -/- mouse model was also examined. Bone quality was evaluated through densitometry, mechanical testing and techniques to assess remodeling, structural and mineral properties. TZD treatment negatively affected trabecular mechanical properties in male, female and ovariectomized female (OVX) mice. Male mice exhibited the greatest effect due to TZD treatment with reduced vertebral vBMD, trabecular structure and bone formation. DPP-4 inhibitor treatment improved vertebral vBMD and trabecular architecture in female mice but improvements were lost in females following OVX. Male, female and OVX mice experienced increased trabecular mineralization due to DPP-4 inhibitor treatment. Genetic inactivation of DPP-4 did not produce a major bone phenotype in male and female mice but lead to reduced femoral geometry and mechanics in OVX mice.

This study characterized the effects of two anti-diabetic drugs, a thiazolidinedione (TZD) and a Dipeptidyl Peptidase-4 (DPP-4) inhibitor on bone quality in a glucose intolerant mouse model. Bone quality in a DPP-4 -/- mouse model was also examined. Bone quality was evaluated through densitometry, mechanical testing and techniques to assess remodeling, structural and mineral properties. TZD treatment negatively affected trabecular mechanical properties in male, female and ovariectomized female (OVX) mice. Male mice exhibited the greatest effect due to TZD treatment with reduced vertebral vBMD, trabecular structure and bone formation. DPP-4 inhibitor treatment improved vertebral vBMD and trabecular architecture in female mice but improvements were lost in females following OVX. Male, female and OVX mice experienced increased trabecular mineralization due to DPP-4 inhibitor treatment. Genetic inactivation of DPP-4 did not produce a major bone phenotype in male and female mice but lead to reduced femoral geometry and mechanics in OVX mice.

There is a pressing need for better assessment of bone strength as current clinical tools do not directly measure bone mechanical properties, but offer only surrogate measures of bone strength. We conducted an ex-vivo study of emu bones to examine how two investigative devices, hr-pQCT and MRTA, compare to current clinical tools (DXA and QUS) in predicting true bone mechanical properties. We found that hr-pQCT parameters were able to assess bone strength as well as DXA and better than QUS, while MRTA was able to predict bone strength well in low-density but not high-density bones. Our results suggest that both hr-pQCT, which has the unique ability to specifically assess the various determinants of bone strength, and MRTA, which measures a bone mechanical property (stiffness), have great potential for use as clinical tools that can assess various components of bone strength not measured by current devices.

Diss. (sammanfattning) Umeå : Umeå universitet, 2006. / Härtill 4 uppsatser.

Submitted by VINÍCIUS CARNEIRO DE SOUZA null (vinicius2042@hotmail.com) on 2016-04-26T15:43:21Z No. of bitstreams: 1 Dissertação Vinícius Carneiro.pdf: 1220037 bytes, checksum: 07a5b46e9340e72b825c419811e26eb9 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-04-28T16:21:12Z (GMT) No. of bitstreams: 1 souza_vc_me_jabo.pdf: 1220037 bytes, checksum: 07a5b46e9340e72b825c419811e26eb9 (MD5) / Made available in DSpace on 2016-04-28T16:21:12Z (GMT). No. of bitstreams: 1 souza_vc_me_jabo.pdf: 1220037 bytes, checksum: 07a5b46e9340e72b825c419811e26eb9 (MD5) Previous issue date: 2016-02-29 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Este estudo avaliou o efeito da suplementação fosfórica (SP) sobre o consumo de nutrientes, desempenho, parâmetros ósseos, qualidade de carne e a utilização do fósforo (P) por bovinos Nelores, durante o período de confinamento. Para tanto, utilizou-se 42 novilhos com peso médio inicial de 296±25 kg distribuídos em delineamento inteiramente casualizado com 3 tratamentos e 14 repetições. A dieta era formada por bagaço de cana (200g/kg na MS) e concentrado (800g/kg na MS). Os tratamentos dietéticos foram: sem a adição de P suplementar (T1), núcleo mineral comercial (T2) e fosfato bicálcico (T3). Os teores porcentuais de P na MS foram 0,24; 0,42 e 0,50, respectivamente. Foram avaliados os consumos de MS, PB, FDN, Ca, P e Mg, bem como a absorção aparente, retenção, excreção fecal e urinária de P, o desempenho animal e as características da carcaça. As avaliações da qualidade óssea consistiram na determinação da composição química óssea, densidade mineral óssea (DMO) e densidade em água (DA), além dos valores séricos de cálcio (Ca), P, magnésio (Mg), paratormônio (PTH), fosfatase alcalina (FA) e a concentração de P na saliva e no líquido ruminal. Os consumos de MS, PB e FDN foram similares entre os grupos que receberam ou não a SP (P>0,05). As ingestões de Ca e Mg foram superiores nos tratamentos em que se adicionou o núcleo comercial ou o fosfato bicálcico (P<0,05). O consumo, a retenção e a excreção de P foram influenciados pelo aumento do teor de P nas dietas experimentais (P<0,05). O desempenho e as características de carcaça não foram afetados pelo teor de P na dieta (P>0,05). A suplementação com P aumentou significativamente a excreção de P através das fezes e da urina e os custos da dieta. Os animais submetidos ou não à suplementação fosfórica, tiveram teores de Ca, relação Ca:P e DMO da 12ª costela semelhantes (P>0,05). No entanto, os animais dos tratamentos T1 e T3 tiveram redução dos teores de magnésio nas costelas ao longo do estudo (P<0,05). Os animais do tratamento sem fósforo suplementar tiveram menor espessura da cortical dos metacarpos (P<0,05), sem comprometer a sua resistência e rigidez (P>0,05). Durante todo o período experimental, nenhum animal foi positivo no teste da agulha realizado nos processos transversos das vértebras lombares. Não houve efeito da suplementação fosfórica sobre a concentração de Ca e P no soro dos animais (P>0,05). Porém, a inclusão de núcleo mineral no tratamento T2 resultou em maior concentração de Mg no soro (P>0,05). A suplementação fosfórica alterou de forma significativa os níveis de paratormônio (PTH) e fosfatase alcalina (FA) no soro (P<0,05) e os animais do tratamento T1 tiveram as menores concentrações circulantes destes hormônios. Nas condições brasileiras, bovinos confinados ingerindo elevadas quantidades de concentrados não necessitam de suplementação com P e o teor de P (0,24 % na MS), utilizado no tratamento sem P suplementar foi suficiente para atender as exigências dietéticas dos animais. Menores teores de P podem até serem adequados, mas não foram testados neste estudo. A suplementação com P aumentou consideravelmente a excreção de P através das fezes e urina e os custos com alimentação dos animais. / The present study was conducted to evaluate the effect of phosphorus supplementation (PS) on nutrient intake, performance and phosphorus (P) utilization by Nellore steers in a feedlot. Forty-two animals with an initial body weight of 296±25 kg were distributed in a completely randomized design consisting of 3 treatments and 14 replicates. The diet on a DM basis was comprised of sugarcane bagasse (200 g/kg) plus concentrate (800 g/kg). The treatments were without supplementary P (T1), commercial mineral supplement specific for feedlot cattle (T2) and dicalcium phosphate (T3) with 0.24, 0.42 or 0.50 % P, respectively. The DM, CP and NDF intakes were similar between the groups with or without the PS (P>0.05). The highest intakes of Ca and Mg were observed in the treatments with commercial mineral supplement or dicalcium phosphate. Intake, retention and excretion of P were influenced by the increase in P content in the experimental diets (P<0.05). Performance and carcass characteristics were not affected by P content in the diet (P>0.05). Supplementation with P significantly increased the excretion of P in the feces and urine and the feeding cost. Therefore, under Brazilian conditions, there is no justification for supplementing P in feedlot rations. The animals submitted or not to phosphorus supplementation had a similar content of Ca, Ca:P ratio and bone mineral density (BMD) at the 12th rib (P>0.05). However, animals of the T1 and T3 treatments had significant reductions in magnesium contents in the rib throughout the study (P<0.05). The animals from treatment without phosphorus supplement had lower cortical thickness of the metacarpal bone (P<0.05), without compromising its resistance and stiffness (P>0.05). Throughout the trial period, no animals were positive in the needle test in the transverse processes of the lumbar vertebrae. There was no effect of phosphorus supplementation on the concentration of Ca and P in the serum of animals (P>0.05). However, the inclusion of commercial mineral supplement in T2 treatment resulted in higher Mg concentration in serum of animals (P>0.05). The phosphorus supplementation significantly changed the levels of parathyroid hormone (PTH) and alkaline phosphatase (AP) levels (P<0.05) and the animals of the T1 treatment had smaller circulating concentrations of these hormones. Under Brazilian conditions, feedlot beef cattle do not appear to require P supplements and a value of P (2.4 g/kg DM), as used in the control diet, appears adequate. Lower values may also be appropriate but were not tested here. Phosphorus supplementation significantly increased the feeding costs, P excretion in the feces and urine and therefore resulted in economic losses. / FAPESP: 2014/08935-1