Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-02Bitstream added on 2014-06-13T20:57:16Z : No. of bitstreams: 1 tera_tm_me_sjc.pdf: 2944672 bytes, checksum: 538ffaa6e20676a8e7a52d38fd5e1b66 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O estudo avaliou a expressão imunoistoquímica dos marcadores de formação óssea Osteocalcina (OCC), Osteonectina (ONC) e Sialoproteína Óssea (BSP), e do marcador de reabsorção óssea Ligante do Receptor Ativador do Fator Nuclear Kappa-β (RANKL) no processo de reparo do enxerto ósseo autógeno em bloco, recoberto ou não por membrana de Politetrafluoretileno expandido (PTFE-e), em ratas com deficiência estrogênica induzida. Para tanto, foram avaliadas espécimes de Enxerto Ósseo Autógeno (EOA) recobertos ou não por membrana de PTFE-e, provenientes de 80 ratas, divididas aleatoriamente em 2 grupos (OVZ e SHAM). As 40 ratas pertencentes ao grupo OVZ foram submetidas à cirurgia de ovariectomia e as 40 do grupo SHAM à cirurgia de ovariectomia simulada. Os dois grupos foram subdivididos em E, onde foi realizada cirurgia para colocação de EOA, e grupo ME, onde o EOA foi recoberto por membrana de PTFE-e. Os períodos avaliados foram dia 0, 7, 21, 45 e 60 dias. Os espécimes foram incluídos em parafina, para realização de cortes seriados com 3 μm de espessura, que foram estendidos em lâminas previamente tratadas pelo 3-aminopropiltrietoxisilano e então foram submetidos à técnica imunoistoquímica para os marcadores OCC, BSP, ONC e RANKL. Os resultados mostraram marcação mais intensa da BSP nos dias 7 e 21. No sétimo dia, observou-se marcação intensa da ONC e RANKL, enquanto a OCC mostrou maior positividade nos dois últimos períodos. No último período avaliado, as características de marcação quanto à intensidade e às estruturas marcadas se assemelharam com os períodos iniciais para todos os marcadores. Os resultados permitiram concluir que o metabolismo ósseo foi mais intenso entre os dias 7 e 21, enquanto a maior taxa de remodelação foi observada aos 7 dias. A partir do 45º dia, o osso neoformado já exibia características de osso maduro. A expressão... / The study evaluated the immunohistochemical expression of bone formation markers Osteocalcin (OCC), Osteonectin (ONC) and Bone Sialoprotein (BSP) and the marker of bone resorption Receptor Activator of Nuclear Factor Kappa-β Ligand (RANKL) in the repair process autogenous bone grafts in blocks covered or not by polytetrafluoroethylene membrane (PTFE-e), in rats with estrogen deficiency induced. For this, 80 famale rats were divided randomly into two groups (SHAM and OVZ). The 40 rats in the group OVZ underwent surgical ovariectomy and 40 of the SHAM group underwent to surgical sham ovariectomy. The two groups were subdivided into E, where surgery was performed for placement of ABG, and ME group, where the ABG was covered with PTFE-e membrane. The evaluation periods were days 0, 7, 21, 45 and 60 days. The specimens were embedded in paraffin, to perform serial sections with 3 mm thick, which were extended on slides previously treated by 3-aminopropiltrietoxisilano and then were subjected to immunohistochemical technique for th markers for the OCC, BSP, ONC and RANKL. The results showed more intense labeling of the BSP on days 7 and 21. On the seventh day, there was intense labeling of the ONC and RANKL, while the OCC showed higher positivity in the last two periods. In the last period evaluated, the characteristics of marking on the intensity and the structures resembled marked with initial periods for all markers. The results showed that the bone metabolism was most intense between days 7 and 21, while the highest rate of remodeling was observed at 7 days. From the 45th day, the newly formed bone already displayed characteristics of mature bone. The expression of immunohistochemical markers was not altered by estrogen deficiency, but rather by the presence of PTFE-e membrane

Resumo: O estudo avaliou a expressão imunoistoquímica dos marcadores de formação óssea Osteocalcina (OCC), Osteonectina (ONC) e Sialoproteína Óssea (BSP), e do marcador de reabsorção óssea Ligante do Receptor Ativador do Fator Nuclear Kappa-β (RANKL) no processo de reparo do enxerto ósseo autógeno em bloco, recoberto ou não por membrana de Politetrafluoretileno expandido (PTFE-e), em ratas com deficiência estrogênica induzida. Para tanto, foram avaliadas espécimes de Enxerto Ósseo Autógeno (EOA) recobertos ou não por membrana de PTFE-e, provenientes de 80 ratas, divididas aleatoriamente em 2 grupos (OVZ e SHAM). As 40 ratas pertencentes ao grupo OVZ foram submetidas à cirurgia de ovariectomia e as 40 do grupo SHAM à cirurgia de ovariectomia simulada. Os dois grupos foram subdivididos em E, onde foi realizada cirurgia para colocação de EOA, e grupo ME, onde o EOA foi recoberto por membrana de PTFE-e. Os períodos avaliados foram dia 0, 7, 21, 45 e 60 dias. Os espécimes foram incluídos em parafina, para realização de cortes seriados com 3 μm de espessura, que foram estendidos em lâminas previamente tratadas pelo 3-aminopropiltrietoxisilano e então foram submetidos à técnica imunoistoquímica para os marcadores OCC, BSP, ONC e RANKL. Os resultados mostraram marcação mais intensa da BSP nos dias 7 e 21. No sétimo dia, observou-se marcação intensa da ONC e RANKL, enquanto a OCC mostrou maior positividade nos dois últimos períodos. No último período avaliado, as características de marcação quanto à intensidade e às estruturas marcadas se assemelharam com os períodos iniciais para todos os marcadores. Os resultados permitiram concluir que o metabolismo ósseo foi mais intenso entre os dias 7 e 21, enquanto a maior taxa de remodelação foi observada aos 7 dias. A partir do 45º dia, o osso neoformado já exibia características de osso maduro. A expressão... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The study evaluated the immunohistochemical expression of bone formation markers Osteocalcin (OCC), Osteonectin (ONC) and Bone Sialoprotein (BSP) and the marker of bone resorption Receptor Activator of Nuclear Factor Kappa-β Ligand (RANKL) in the repair process autogenous bone grafts in blocks covered or not by polytetrafluoroethylene membrane (PTFE-e), in rats with estrogen deficiency induced. For this, 80 famale rats were divided randomly into two groups (SHAM and OVZ). The 40 rats in the group OVZ underwent surgical ovariectomy and 40 of the SHAM group underwent to surgical sham ovariectomy. The two groups were subdivided into E, where surgery was performed for placement of ABG, and ME group, where the ABG was covered with PTFE-e membrane. The evaluation periods were days 0, 7, 21, 45 and 60 days. The specimens were embedded in paraffin, to perform serial sections with 3 mm thick, which were extended on slides previously treated by 3-aminopropiltrietoxisilano and then were subjected to immunohistochemical technique for th markers for the OCC, BSP, ONC and RANKL. The results showed more intense labeling of the BSP on days 7 and 21. On the seventh day, there was intense labeling of the ONC and RANKL, while the OCC showed higher positivity in the last two periods. In the last period evaluated, the characteristics of marking on the intensity and the structures resembled marked with initial periods for all markers. The results showed that the bone metabolism was most intense between days 7 and 21, while the highest rate of remodeling was observed at 7 days. From the 45th day, the newly formed bone already displayed characteristics of mature bone. The expression of immunohistochemical markers was not altered by estrogen deficiency, but rather by the presence of PTFE-e membrane / Orientador: Maria Aparecida Neves Jardini / Coorientador: Renata Falchete do Prado / Banca: Andréa Carvalho de Marco / Banca: Yasmin Rodarte Carvalho / Mestre

Cardiovascular disease (CVD) is the leading cause of death worldwide. Pre-menopausal women have a lower incidence and severity of CVD compared to age-matched men. However, at the onset of menopause, CVD increases. A central feature in patients with CVD is excessive chronic sympathetic stimulation (CSS) of β-adrenergic receptors (β-AR’s). Clinical and animal studies show estrogen deficiency and age exacerbate cardiac β-AR signaling and contractile function. This led to the hypothesis that prolonged estrogen deficiency followed by CSS worsens left ventricular cardiac function and hypertrophy in the aged female heart. Female mice underwent bilateral ovariectomy or SHAM surgery at 2.5 months of age. At 12 months post-ovariectomy, mice were infused with Isoproterenol (400μg/kg/h) via mini-osmotic pumps for three days to induce CSS. This observation demonstrates prolonged estrogen deficiency worsens cardiac function and structure in aged female hearts. Thereby emphasizing the importance of clinical intervention and prevention for CVD in menopausal women.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The risks for women increase at the onset of menopause. A central feature in CVD patients is excessive sympathetic stimulation of beta-adrenergic receptors (β-ARs). Both clinical and animal studies show that estrogen loss and age exacerbate cardiac β-AR signaling and contractile function. We, therefore, examined the hypothesis that prolonged estrogen deficiency followed by chronic sympathetic injury worsens left ventricular cardiac function in the aged female heart. Bilateral ovariectomy (OVX) or SHAM surgery was performed in female mice at 2.5 months of age and infused with Isoproterenol (ISO; 400μg/kg/h) at 12 months (12M) post OVX for 3 days to induce chronic sympathetic stimulation. Transthoracic two-dimensional M-mode echocardiography was used to measure left ventricular (LV) wall thickness and left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD), percent fractional shortening (%FS), and ejection fraction (EF). Animal body weight was measured to calculate the heart-body ratio, followed by the removal of the heart, left lung, and uterus during euthanasia. Tissue samples were treated with wheat germ agglutinin staining to measure cardiac myocyte cross-sectional area (hypertrophy). Results show that prolonged ovariectomy increased mortality in mice treated with ISO post-ovariectomy (OVX +ISO) compared to the SHAM+ISO group. Echocardiography imaging demonstrated a smaller systolic diameter and increased contractility in the ISO and ISO+OVX groups. OVX, ISO, and ISO+OVX treatment had a significant decrease in LVESD versus SHAM and OVX groups. The LVEDD resulted in a significant decrease with ISO treatment compared to the SHAM group, and no significant difference was observed between the OVX and ISO+OVX groups compared to the SHAM. Percent FS presented a significant increase in cardiac function in OVX, ISO, and ISO+OVX groups compared to the SHAM. There was an increased %FS in the ISO+OVX compared to the OVX group, and no significant difference between the ISO+OVX and ISO treatment groups. Percent EF significantly increased in the OVX, ISO, and ISO+OVX treatment groups from the SHAM and OVX group, and no significant difference between the ISO+OVX and ISO treatment groups. OVX increased left ventricular mass compared to SHAM. While ISO treatment did not increase LV mass ISO+OVX treatment group significantly increased in LV mass when compared to the ISO treatment group. There was no significant difference in the left ventricular mass between the ISO+OVX vs. OVX group. There was no significant difference in cardiac myocyte cross-sectional area in the SHAM, OVX vs ISO groups. There was however a significant increase in myocyte cross-sectional area in the ISO+OVX group compared to OVX treatment and ISO groups. The results presented here show that estrogen loss impairs left ventricular cardiac function and increases remodeling in response to β-AR stimulation and that prolonged estrogen loss may blunt the sympathetic response in the heart. These results highlight the importance of the long-term effects of estrogen loss during menopause in the treatment and management of heart disease.

Made available in DSpace on 2014-06-11T19:28:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2004Bitstream added on 2014-06-13T18:32:28Z : No. of bitstreams: 1 luize_ds_me_araca.pdf: 1486325 bytes, checksum: 476beff7c6d682441474e7e924d333a5 (MD5) / Universidade Estadual Paulista (UNESP) / O objetivo do presente estudo foi avaliar, por meio de análise histológica, a influência da ovariectomia (depleção de estrógeno) no processo de reparo de enxertos ósseos autógenos em bloco. Para isso, foram utilizadas 36 ratas fêmeas, com idade de 12 meses, divididas em grupo controle (GC) e grupo experimental (GE) de 18 animais cada. As ratas do GE foram submetidas à cirurgia de ovariectomia (Ov), enquanto as ratas do GC foram submetidas a simulação do mesmo procedimento cirúrgico, sem a remoção dos ovários (Si). Transcorridos 30 dias da Ov ou Si, todos os animais receberam enxerto ósseo autógeno em bloco na mandíbula, na região próxima ao ângulo, tendo como área doadora o osso parietal da calvária. Os animais de cada grupo foram divididos em subgrupos de 6 animais, os quais foram submetidos à eutanásia nos períodos de 7, 14 e 28 dias, após a realização do enxerto ósseo. Aos 7 dias, a interface enxerto-leito receptor no GC mostrou-se preenchida por um típico tecido de granulação, com discreta atividade de angiogênese na porção central, ao passo que no GE, havia ainda a presença de coágulo sanguíneo e um tecido de granulação em organização. Aos 14 dias, no GC, a interface apresentou-se parcialmente preenchida por matriz óssea neoformada, estabelecendo uma união do enxerto ao leito receptor, enquanto que no GE, a maior parte da interface encontrou-se preenchida por um típico tecido de granulação com nítida angiogênese e discreta atividade osteogênica, com neoformação de matriz óssea em algumas áreas. Aos 28 dias, o enxerto no GC apresentou-se histologicamente integrado ao leito receptor, com acentuada atividade osteogênica, ao passo que no GE a interface apresentou-se parcialmente preenchida por matriz óssea neoformada, encontrando-se também áreas de tecido conjuntivo entre o enxerto e o leito receptor... / The aim of this study was to investigate, by means of histological analysis, the influence of ovariectomy (estrogen depletion) on the repair process of autogenous block bone grafts. 36 female adult rats, age twelve months, were assigned to two groups (n=18): control group (CG) and experimental group (EG). The rats in the EG had an ovariectomy (Ovx) whereas those in the CG underwent the same surgical intervention but did not have their ovaries removed (Sham). Thirty days after Ovx or Sham all the animals received autogenous block bone grafts in the mandible, in the region near the mandibular angle. The donor area was the parietal bone. The animals of each group were euthanized at 7, 14 and 28 days postoperative. On the 7th postoperative day, the graft-recipient site interface in the CG appeared filled by a typical granulation tissue with discreet angiogenic activity in the central portion whereas the EG still exhibited a blood clot and an organizing granulation tissue. On the 14th postoperative day, the interface in the CG was partially filled with newly formed bone matrix establishing a union between the graft and the recipient site. The majority of the interface in the EG was filled by a typical granulation tissue with evident angiogenic activity, discreet osteogenic activity and newly formed bone matrix in some areas. On the 28th postoperative day, the graft in the CG appeared histologically integrated with the recipient site and exhibited pronounced osteogenic activity. On the other hand, the interface in the EG appeared partially filled by newly formed bone matrix with areas of connective tissue observed as well. Within the limitations of the study, it may be concluded that estrogen depletion caused by the ovariectomy hindered the healing process of autogenous block bone grafts placed in the mandible of female adult rats... (Complete abstract, click electronic address below)

Submitted by Aelson Maciera (aelsoncm@terra.com.br) on 2017-06-19T19:07:25Z No. of bitstreams: 1 TeseGFDP.pdf: 2245329 bytes, checksum: 53db7c3a23993db1750501f68d55101a (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-26T18:16:01Z (GMT) No. of bitstreams: 1 TeseGFDP.pdf: 2245329 bytes, checksum: 53db7c3a23993db1750501f68d55101a (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-26T18:16:31Z (GMT) No. of bitstreams: 1 TeseGFDP.pdf: 2245329 bytes, checksum: 53db7c3a23993db1750501f68d55101a (MD5) / Made available in DSpace on 2017-06-26T18:22:15Z (GMT). No. of bitstreams: 1 TeseGFDP.pdf: 2245329 bytes, checksum: 53db7c3a23993db1750501f68d55101a (MD5) Previous issue date: 2016-12-09 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Absence of estrogen on menopause leads to detrimental consequences, including osteoporosis, which is characterized by unbalanced bone extracellular matrix (ECM) remodeling. Bone resistance to fracture is related to bone mass, structure and architecture including bone ECM changes. Resistance training (RT) has shown beneficial effects on prevention and treatment of osteoporosis, however, there are few studies regarding RT role in bone remodeling in different scales, such as bone composition and structure until matrix metalloproteinases (MMPs) in ovariectomy (OVX) model. Aims: To evaluate RT effects on bone properties, morphology and bone ECM remodeling markers in an OVX rat model. Methods: Thirty six female Sprague Dawley rats were divided into four groups: sham sedentary, OVX sedentary, sham RT and OVX RT. Rats performed RT for 10 weeks in which they climbed a ladder with progressive loads attached to the tails. Tibias were stored for biometrical, biomechanical, biophysical and biochemical analysis. Femurs were stored to morphological, gene expression and gelatin zymography analysis. Results: OVX decreased bone mineral density, bone mineral content, stiffness, maximal load, calcium content, trabecular number and connectivity and MMP-13 gene expression. Furthermore, OVX increased RUNX-2 and OPG gene expression and MMP-2 activity. RT was efficient in prevent or reverse almost all of alterations. Conclusion: Estrogen absence osteoporosis affects bone mass and other factors involved in bone ECM remodeling and RT showed be efficient in prevent or reverse these harmful effects. / A queda nos níveis de estrogênio durante a menopausa pode acarretar em prejuízos, incluindo a osteoporose, caracterizada por um desbalanço no remodelamento da matriz extracelular (MEC) óssea. A resistência óssea à fratura está relacionada não somente com a massa, estrutura e arquitetura ósseas, mas tambem com alterações na MEC óssea. O treinamento resistido (TR) tem mostrado benefícios na prevenção e tratamento da osteoporose, entretanto poucos trabalhos são dedicados a relacionar o papel do TR no remodelamento ósseo em diversas escalas como composição material óssea, estrutura e o papel das metaloproteinases de matriz (MMPs) em modelo de ovariectomia (OVX). Objetivos: Avaliar os efeitos do TR na morfologia e propriedades ósseas e em marcadores de remodelamento da MEC óssea em modelo de ratas OVX. Métodos: Trinta e seis ratas da linhagem Sprague Dawley foram divididas em quarto grupos: sham sedentário, OVX sedentário, sham TR e OVX TR. As ratas foram submetidas a 10 semanas de TR com subida em escada com cargas progressivamente maiores atadas à cauda. As tíbias foram armazenadas para análises de biometria, biomecânica, biofísica e bioquímica. Os fêmures foram armazenados para análises de morfologia, expressão gênica e zimografia em gelatina. Resultados: A OVX promoveu um decréscimo dos seguintes parâmetros: densidade mineral óssea, conteúdo mineral ósseo, rigidez, carga máxima, conteúdo de cálcio, número e conectividade trabecular e expressão de MMP-13 e aumento da porcentagem de água, separação trabecular, expressão gênica de RUNX-2 e OPG e atividade de MMP-2. O TR se mostrou eficaz em prevenir ou reverter praticamente todas as alterações. Conclusão: A osteoporose advinda da queda dos hormônios ovarianos afeta não somente a massa óssea, mas também fatores envolvidos no remodelamento da MEC óssea e o TR se mostrou eficaz em prevenir ou reverter tais efeitos.

No description available.

Osteoporosis which is frequently referred to as a pediatric disease with geriatric consequences (Golden, 2000) can result from a lack of optimal bone accrual during the development (NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, 2001). Pubertal timing is a key factor that contributes to optimal bone accrual and strength (Bonjour et al., 1994; 21 Warren et al., 2002). Bone mass doubles during the onset of puberty and young adulthood (Katzman et al., 1991) with more than 90% of peak bone mass being accrued at the end of second decade of life (Schneider & Wade, 2000). The rate of periosteal expansion is elevated during the pubertal period (Specker et al., 1987; Bradney et al., 2000) and this expansion parallels longitudinal growth (Parfitt, 1994). Irrespective of other changes, periosteal expansion lowers fracture risk by improving the strength of long bones by increasing the moment of inertia (Orwoll, 2003). Therefore, a delay in puberty may actually increase the time available for periosteal development and positively affect bone strength. Previous animal studies have shown decreases in strength, endocortical bone formation and increases in periosteal bone formation with delayed puberty. Clinical studies report negative effects of delayed puberty on bone mass accrual suggesting that delayed puberty is a multifactorial problem affecting bone strength development. The purpose of this study was to determine the effect of delayed puberty on mechanical strength and endocortical bone marrow cells in two models: female rats treated with gonadatropin releasing hormone antagonists (GnRH-a) and energy restriction (30%). Thirty-two female Sprague Dawley rats (21 to 22 days-of-age) were received from (Charles Rivers Laboratories, Wilmington, MA, USA) and housed individually at the Temple University Central Animal Facility (Temple University Weiss Hall). Animals were randomly assigned to one of three groups; control (n=10), GnRH-a (n=10) and energy restriction (ER) (n=12). The GnRH-a group was injected with gonadotropin releasing antagonist injections (GnRH-a) (Antide, Bachem, Torrance, Ca. USA) at a dose of 2.5 mg/kg/BW. The ER group received a 30% energy restricted diet (0pen Source diet (D07100606)(Research Diets, New Brunswick, NJ). All animals were sacrificed on Day 51. One way analysis of variance testing (ANOVA) with a significance level of 0.05 was used to assess group differences. Following the two protocols the uterine weight in the GnRH-a group was 80.6% lower than control; no change in the ER group. Ovarian weight was significantly lower in the GnRH-a group (83.3%) and in the ER group (33.3%) as compared to controls. A 22.7% lower muscle weight was found in the ER group but was equal to control and GnRH-a when normalized by body weight (BW). The retro-peritoneal fat pad weight was significantly decreased by 64.95% in the ER group as compared to controls. Energy restriction did not result in any deficit in bone strength when normalized by body weight however the GnRH-a group had a 26.2% lower bone strength compared to control. Histomorphometric changes were not significantly different between groups, but the ratio for periosteal versus endocortical bone formation rates for the control group was 1.38, GnRH-a was significantly higher with a ratio of 5.54 and for ER was 3.02 indicating that periosteal BFR are almost twice endocortical BFR in the experimental groups. There was a significant decrease in the trabecular percent bone volume (BV/TV) of the lumbar vertebra in the GnRH-a group (20.2%) compared to control. However BV/TV was significantly higher in the ER (18.4%) compared to the control group. Proliferation was suppressed to 59.6% of control in the GnRH-a group but only 85.5% of control in the ER group. The alkaline phosphatase activity was 31.2% lower in the GnRH-a group and 63.9% lower in the ER group. The relative quantification (RQ) of RUNX2 gene expression was lowest in control followed by GnRH-a and highest in ER group although no statistical significance was observed between any groups. Thus our data infers that 30% energy restriction does not negatively impact bone health. Thirty percent food restriction with no deficits in micronutrients or hormone suppression may just suppress growth as indicated by the maintenance of bone strength per body weight and equivalent muscle mass per body weight in the ER group compared to control. The GnRH-a injections resulted in decreased bone strength and trabecular bone volume. Female Athlete Triad or Anorexia Nervosa are the two clinical conditions hypothesized to result from a combination of ER and estrogen deficient environment. Studies replacing estrogen in hypothalamic amenorrhea or IGF-1 in anorexia alone have failed to improve bone mineral density (BMD), but a combination of IGF-1 and estrogen has been successful in improving BMD. This suggests that estrogen dependant and independent mechanisms work in combination to protect bone. Our study investigated both mechanisms separately and indicates that ER at 30% may be protective for bone health. Since estrogen deficiency may be the extreme end of the spectrum affecting trabecular bone, treatment therapies may have to be based on age, magnitude and severity of energy restriction and presence or absence of menstrual status. / Kinesiology

Bone formation and bone healing were studied in the mandible, tibia and skull bones in adult, healthy and estrogen deficient rabbits implanted with different bone substitutes. In the first study an evaluation of the differences in bone regeneration in and around solid (Alveograf *) and porous hydroxyapatite (Interpore 200*) was undertaken. The implant material was placed into experimentally made bone defects and in half of the defects hydroxyapatite was mixed with a fibrin sealant (Tisseel *). The material alone or mixed with Tisseel was also placed subperiostally in the mandible. The observation time was six month. No difference in bone regeneration was found between solid or porous hydroxyapatite granulas and the addition of Tisseel* did not seem to disturb the bone healing process. The implant material placed subperiostally did not induce bone formation nor did it provoke any bone resorption. The addition of Tisseel made the implant material much easier to handle and retain in the tissue during surgery. Bone healing around hydroxyapatite implants was also evaluated in the second study. Experimental cavities in the mandible and tibia were filled with hydroxyapatite in granules or blocks (Interpore 200*) but now with or without autolyzed, antigen-extracted, allogeneic bone (AAA). Also in this study Tisseel* was used to facilitate the handling of the material. All cavities implanted with AAA-bone, regardless of the combination with hydroxyapatite or Tisseel, demonstrated excessive bone formation resembling exostosis formation. Thus, hydroxyapatite, both as granules and blocks, can be successfully combined with AAA bone utilizing the bone inductive capacity of AAA bone. The same model was used to study the healing in ovariectomized animals in the third study. Bone cavities were implanted with or without AAA bone and left to heal. The results indicate that the osteoinductive capacity of AAA bone is in operation also in animals deprived of a normal estrogen production. The effect of using AAA bone prior to implant insertion was studied in paper four. The bone-implant contact was significant higher when AAA bone had been used. The implant stability did not seem to be affected. In paper five defects were made in skull and tibial bone in estrogen deficient animals. The deficiency of estrogen was confirmed through blood analysis, the decrease in the weight of uterus and bone mineral density. The whole body scanning with DEXA showed that the ovariectomized animals developed osteopenia. Various degree of bone formation was seen in the defects due to the influence of the bone inductive substance AAA bone. The studies indicate that a conductive material like hydroxyapatite in granules or blocks could be useful in oral reconstructive surgery. The combination with AAA bone enhanced the bone formation in calvarial and tibial bone in healthy and estrogen deficient animals. Tisseel* could be used to facilitate handling and retention of the material in the intended position during the healing process without negative effects.

<p>Bone formation and bone healing were studied in the mandible, tibia and skull bones in adult, healthy and estrogen deficient rabbits implanted with different bone substitutes. </p><p>In the first study an evaluation of the differences in bone regeneration in and around solid (Alveograf *) and porous hydroxyapatite (Interpore 200*) was undertaken. The implant material was placed into experimentally made bone defects and in half of the defects hydroxyapatite was mixed with a fibrin sealant (Tisseel *). The material alone or mixed with Tisseel was also placed subperiostally in the mandible. The observation time was six month. No difference in bone regeneration was found between solid or porous hydroxyapatite granulas and the addition of Tisseel* did not seem to disturb the bone healing process. The implant material placed subperiostally did not induce bone formation nor did it provoke any bone resorption. The addition of Tisseel made the implant material much easier to handle and retain in the tissue during surgery.</p><p>Bone healing around hydroxyapatite implants was also evaluated in the second study. Experimental cavities in the mandible and tibia were filled with hydroxyapatite in granules or blocks (Interpore 200*) but now with or without autolyzed, antigen-extracted, allogeneic bone (AAA). Also in this study Tisseel* was used to facilitate the handling of the material. All cavities implanted with AAA-bone, regardless of the combination with hydroxyapatite or Tisseel, demonstrated excessive bone formation resembling exostosis formation. Thus, hydroxyapatite, both as granules and blocks, can be successfully combined with AAA bone utilizing the bone inductive capacity of AAA bone.</p><p>The same model was used to study the healing in ovariectomized animals in the third study. Bone cavities were implanted with or without AAA bone and left to heal. The results indicate that the osteoinductive capacity of AAA bone is in operation also in animals deprived of a normal estrogen production.</p><p>The effect of using AAA bone prior to implant insertion was studied in paper four. The bone-implant contact was significant higher when AAA bone had been used. The implant stability did not seem to be affected.</p><p>In paper five defects were made in skull and tibial bone in estrogen deficient animals. The deficiency of estrogen was confirmed through blood analysis, the decrease in the weight of uterus and bone mineral density. The whole body scanning with DEXA showed that the ovariectomized animals developed osteopenia. Various degree of bone formation was seen in the defects due to the influence of the bone inductive substance AAA bone. </p><p>The studies indicate that a conductive material like hydroxyapatite in granules or blocks could be useful in oral reconstructive surgery. The combination with AAA bone enhanced the bone formation in calvarial and tibial bone in healthy and estrogen deficient animals. Tisseel* could be used to facilitate handling and retention of the material in the intended position during the healing process without negative effects. </p>