Peripheral artery disease (PAD) and osteoporosis have recently been shown to be associated; with the parallel occurrence suggesting that PAD related ischemia may cause or enhance the onset of osteoporosis. In order to determine the mechanism linking osteoporosis and PAD this paper will examine the effects of ischemia and mechanical stimulation on bone remodeling. An immunohistochemistry protocol for vessel marking in bone was also developed. Ischemia was induced in a mouse model to determine vascular and mechanical property changes in bone in response to hypoxia, and mechanical loading-induced remodeling was analyzed for vascular changes. Both ischemia and mechanical loading increased bone vessel density, with ischemic bone increases seen at day 7 and 14. Bone stiffness increased after induced ischemia at day 28. These results point to resultant hypoxia from ischemia drives bone mechanical property changes, likely through stimulation of bone remodeling. We also conclude that an increase in vessel density is seen after induced mechanical loading of bone. Establishing the vascular contribution to the remodeling process may reveal treatment opportunities for remodeling-dependent pathologies such as osteoporosis.

La osteoporosis es una de las enfermedades crónicas más prevalentes en la edad adulta, siendo responsable de una alta tasa de morbilidad y mortalidad. La aparición de la osteoporosis en mujeres posmenopáusicas debido principalmente a la disminución de los niveles séricos de estrógeno ha sido propuesta como un factor de riesgo de la enfermedad periodontal, sin embargo, la relación entre estas dos enfermedades no está del todo clara. El objetivo del presente estudio fue el de comparar el grado de periodontitis entre mujeres posmenopáusicas con osteoporosis y mujeres posmenopáusicas sin osteoporosis que acudieron al Servicio de Reumatología del Hospital Nacional Edgardo Rebagliati Martins durante diciembre del año 2003. La población estudiada incluyó 40 mujeres posmenopáusicas con osteoporosis y 40 mujeres posmenopáusicas sin osteoporosis, con edades entre los 50 y 55 años (edad promedio: grupo con osteoporosis: 52.40 ± 1.22 años, grupo sin osteoporosis: 52.25 ± 1.13 años). La condición de osteoporosis fue determinada por la medición de la Densidad Mineral Ósea (DMO) mediante Absorciometría de Energía Dual de Rayos X (DEXA) en la región de la columna lumbar. La severidad de la periodontitis fue representada por el Índice de Enfermedad Periodontal de Ramfjord (PDI) y la Pérdida de Adherencia Clínica (PAC). Otras mediciones periodontales incluyeron la cuantificación de placa y cálculo expresados a través del Índice de Higiene Oral Simplificado de Green y Vermillon (IHO-S). Los exámenes periodontales y de DEXA fueron realizados por examinadores calibrados. Se utilizó la prueba t-student para comprobar la relación entre el grado de periodontitis y la osteoporosis. El presente estudio encontró una diferencia estadísticamente significativa del índice de enfermedad periodontal entre mujeres posmenopáusicas con y sin osteoporosis (p<0.05). De otro lado, al caracterizar la asociación entre el índice de enfermedad periodontal y la pérdida de adherencia clínica con los niveles clínicos de higiene oral para ambos grupos de mujeres, se encontraron diferencias estadísticamente significativas en el grupo de mujeres posmenopáusicas con osteoporosis (p<0.05), a diferencia del grupo de mujeres posmenopáusicas sin osteoporosis (p>0.05). Estos hallazgos sugieren que existe una relación directa entre la osteoporosis y la gravedad de la periodontitis en mujeres posmenopáusicas, es decir que la condición de osteoporosis en este grupo de mujeres está asociada a un mayor grado de severidad de la periodontitis, luego de haber controlado factores como la edad, edad posmenopáusica, raza e higiene oral. Así mismo, en presencia de niveles clínicos deficientes de higiene oral, las mujeres posmenopáusicas con osteoporosis presentan significativamente un mayor grado de periodontitis en comparación con aquellas con mejores niveles clínicos de higiene oral. Palabras clave: Densidad mineral ósea, pérdida de adherencia clínica, índice de enfermedad periodontal, índice de higiene oral simplificado, osteoporosis, posmenopausia, periodontitis, enfermedad periodontal. / Osteoporosis is one of the more prevalent chronic disease in the adult age, being responsible for a high rate of morbility and mortality. The appearing of the osteoporosis in postmenopausal women owed mainly to the diminution of blood estrogen levels has been propose like a risk factor of the periodontal disease, however, the relation between these two diseases is not absolutely clear. The objective of the present study was to compare the degree of periodontitis between postmenopausal women with osteoporosis and postmenopausal women without osteoporosis who went to the Service of Rheumatology of the Edgardo Rebagliati Martins National Hospital during December 2003. The studied population included 40 postmenopausal women with osteoporosis and 40 postmenopausal women without osteoporosis, with ages between 50 and 55 years old (average age: group with osteoporosis: 52.40 ± 1,22 years old, group without osteoporosis: 52.25 ± 1,13 years old). The condition of osteoporosis was determined by the measurement of the Bone Mineral Density (DMO) by means of Dual Energy X Ray Absorciometry (DEXA) in the region of the lumbar column. The severity of the periodontitis was represented by the Ramfjord´s Periodontal Disease Index (PDI) and the Loss of Clinical Attachment (PAC). Other periodontal measurements included the quantification of plaque and tartar through the Green and Vermillion’s Oral Hygiene Simplified Index (IHO-S). Periodontal and DEXA examinations were made by calibrated examiners. The t-student test was used to verify the relation between the degree of periodontitis and the osteoporosis. The present study found a statistically significant difference of the Index of Periodontal Disease between postmenopausal women with and without osteoporosis (p<0.05). In addition, when the association between the Index of Periodontal Disease and the Loss of Clinical Attachment with Clinical Levels of Oral Hygiene for both groups of women was assessed, statistically significant differences were found in the group of postmenopausal women with osteoporosis (p<0.05), but no differences were found in the group of postmenopausal women without osteoporosis (p>0.05). These findings suggest that exists a direct relation between the osteoporosis and the severity of the periodontitis in postmenopausal women, it means that the condition of osteoporosis in this group of women is associated to a higher degree of periodontitis, after the control of factors like age, postmenopausal age, race and oral hygiene. Additionally, in presence of deficient clinical levels of oral hygiene, postmenopausal women with osteoporosis present a higher degree of periodontitis in comparison with those with better clinical levels of oral hygiene. Key words: Bone mineral density, loss of clinical attachment, index of periodontal disease, simplified index of oral hygiene, osteoporosis, postmenopausal, periodontitis, periodontal disease.

Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains viii, 88 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 81-88).

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also from UMI Company.

Long-term glucocorticoid use leads to glucocorticoid-induced osteoporosis (GIOP) and fractures which require proper management. Little is known about the "real-world," long-term costs and effectiveness of anti-osteoporotic treatments. A retrospective analysis of data from the 1996-2004 Medical Expenditure Panel Survey was conducted to evaluate the "real-world" outcomes. Markov modeling with Monte Carlo simulations was used to yield long-term estimates of these outcomes. A total of 5,461 subjects met the study criteria for long-term glucocorticoid users (LTGS, average prednisone-equivalent dose=11.0 mg/day, average length=237 days), which represents 2.3% of the non-institutional U.S. population. The study subjects tended to be middle-aged (49.7 years old), female (61.4%) and white (86.2%). Overall 22.4% of LTGS users reported use of any anti-osteoporotic agent. Hormone replacement therapy (HRT) was the most frequently used in women followed by bisphosphonates, while bisphosphonates and calcitonin were used by men. Analyses of variance indicated some significant differences in characteristics of LTGS users among treatment groups which suggest a selection bias. Female LTGS users had higher prevalence rates (6.8%) of osteoporosis than males (1.0%), but the prevalence rates of osteoporotic fractures were similar (3.0%). The logistic regression analyses indicated that the use of oral glucocorticoid tablets does not significantly change the odds of osteoporotic fractures in study subjects (relative risk (RR)=1.146, 95% confidence interval (CI) 0.901-1.458 for subjects in the WELL state; RR=0.55, 95% CI 0.188-1.621 for subjects in the GIOP state; RR=1.241, 95% CI 0.532-2.893 for subjects in the GIFX state). The estimated 10-year and lifetime incremental cost per osteoporotic fracture avoided are $27,253-$35,692 (10-year) and $84,942-$91,075 (lifetime) in hypothetical female glucocorticoid users. HRT is the most cost-effective option for hypothetical females except that calcitonin is preferred for 65-year-old females receiving lifetime treatments. When HRT is excluded, calcitonin is the next most cost-effective option except that raloxifene is preferred for 30- and 50-year-old females receiving 10-year treatments. Calcitonin is the most cost-effective option for male glucocorticoid users. Bisphosphonates are less cost-effective which may be due to selection bias. Anti-osteoporotic treatments are recommended for all long-term glucocorticoid users, but the preferred option depends on gender, age, length of treatments and budgets.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Reduced bone mass is a common complication of human inflammatory bowel disease, however, the mechanisms that contribute to osteopenia are not completely understood. Cytokines are up regulated in IBD patients and have been shown to have detrimental effects on osteoblasts. PHEX is expressed predominantly in osteoblasts; disruption of the PHEX gene results in defective bone mineralization and renal phosphate wasting. We hypothesize that PHEX gene expression as well as overall Pi homeostasis are altered in individuals with IBD and therefore, may contribute to alterations in bone mineral density observed in individuals with IBD. In vivo studies: 6-7 week old Balb/C mice were intrarectally instilled with TNBS or 50% ethanol. Animals were treated with or without neutralizing anti-TNFα antibody, dietary curcumin, or systemically with recombinant TNFα. RNA was prepared from bone and gene expression was analyzed by PCR. Kidney and small bowel were harvested from control and TNBS treated animals and embedded in paraffin for immunohistochemical analysis. In vitro studies: Cells were treated with IFNγ, IL1-β, IL-6, or TNFα and RNA was collected for real-time PCR analysis. UMR-106 cells were transfected with Phex promoter constructs. PHEX is down-regulated in mice with chemically induced colitis and in the mice injected with TNFα, this decrease was attenuated by curcumin and TNFα antibody. TNFα decreased endogenous levels of PHEX mRNA, protein, and inhibited spontateous mineralization in UMR-106 cells. This regulation occured at a transcriptional level and it appears that the proximal poly-A region of the PHEX promoter played a significant role in downregulation of Phex expression. Phosphatonin expression was not altered in TNFα-treated UMR-106 osteoblasts. Cytokines were unable to alter phosphatonin mRNA expression in UMR-106 cells and no changes in phosphatonin expression were observed in vivo. Intestinal NaPi-IIb mRNA expression decreased in TNBS-treated animals although immunohistochemical analysis did not reveal any changes in cellular localization of NaPi-IIb protein. Renal NaPi-IIa mRNA did not change in TNBS-treated animals however, immunohistochemical analysis revealed internalization of NaPi-IIa from the apical membrane. In conclusion, decreased phosphate absorption in the kidney along with altered Phex gene expression may contribute to decreased bone mineral density observed in IBD patients.

No description available.

No description available.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 163-184) Also available in print.