The purpose of this study is to further quantify adult ovine ovariectomized bone for new remodeling characteristics to obtain a better understanding of how remodeling is occurring and the effectiveness of this animal model for the study of postmenopausal osteoporosis. Postmenopausal osteoporosis is a major health concern and animal models to test new treatment options are needed. The ovine model is a good option because the ewes undergo Haversian remodeling, are a large sized animal, and have a similar hormone profile to humans. Ewes, however, do not undergo a natural menopause, so an ovariectomy surgery was conducted in the sheep to simulate the decreased levels in estrogen. Columbia-Rambouillet sheep were used in this study: some that have been ovariectomized as a model for postmenopausal osteoporosis and some that underwent a sham surgery to serve as a control. The sheep were sacrificed 12 months post operatively in the month of August, so the seasonal effects of remodeling were accounted for. The left radius was then processed into microradiographs of 6 regional cortical beams, where the cranial (tensile side) and caudal (compressive side) anatomical sections were analyzed in this study to determine regional differences in remodeling. Previous students’ theses have analyzed the similar samples for basic bone remodeling histology measurements, resulting in some significant seasonal, anatomical, and treatment differences. However, most of the results showed no particular increase in the amount of remodeled area for the ovariectomized sheep compared to the sham sheep, even though an ovariectomy is believed to cause a burst of remodeling in bone due to the decreased levels in estrogen. In this study, a new repeatable method was developed that further examines secondary bone by quantifying the extent to which secondary osteons encroach on previously-existing secondary osteons. Encroached and unencroached secondary osteons were quantified using two different methods: a point count method that measured the percentage of the area the encroached and unencroached secondary osteons inhabited and an osteon count method that measured the number of encroached and unencroached secondary osteons per area. These raw measurements were calculated into 18 parameters and 2-way repeated measures ANOVAs were run to determine the effects of surgery and anatomical region on each of the bone remodeling parameters. The results found significant effects from estrogen deletion which were different depending on if the bone region was predominately in compression or tension. The ovariectomy surgery caused an increase in remodeling, which was mostly confined on the compressive side to areas that have been previously remodeled, but on the tensile side, bone remodeling expanded into areas that used to be primary bone. The new secondary osteons, as a result of the ovariectomy surgery, were larger than in the control animals. There however, was not an increase in porosity from the ovariectomy surgery, which is one of the main characteristics of osteoporosis. The model could be further studied to determine what sheep are doing that prevents them from losing bone and that knowledge could be greatly beneficial for human treatment plans of postmenopausal osteoporosis.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Objetivo: Examinar o efeito da hipofunção mastigatória e deficiência estrogênica no osso da mandíbula e comparar esta região com o osso da coluna e fêmur. Métodos: Vinte e quatro ratas Wistar foram ovariectomizadas (OVX) ou Sham-operadas (Sham) e analisadas após alimentação com dietanormal (Pellet) ou dieta-pó (Pó), divididas em 4 grupos: (GI) Sham-Pellet; (GII) OVX-Pelllet; (GIII) Sham-Pó; (GIV) OVX-Pó. A densidade mineral óssea (DMO) foi medida na coluna lombar e fêmur ao início e final do estudo, e a DMO (DMO inicial - DMO final) foi calculada. A DMO do osso mandibular e a histomorfometria foram analisadas ao final do experimento. Resultados: Os animais dos grupos Sham apresentaram DMO maior na coluna (GI:13.5% vs. GII:0.74%, p<0.01; GIII:10.67% vs. GIV:- 4.36%, p<0.001) e fêmur (GI:14.43% vs. GII:4.42%, p<0.01; GIII:10.58% vs. GIV:0.49%, p<0.001) que os dos grupos OVX, mas nenhuma diferença foi observada na DMO da mandíbula entre esses grupos (p>0,05). Por outro lado, os animais dos grupos de dieta-Pó mostraram diminuição da DMO da mandíbula quando comparados com os dos grupos de dieta-Pellet, (GIV vs. GII, p<0,01; GIII vs. GI, p<0,01). Semelhantemente, a análise histomorfométrica do côndilo mandibular mostrou que os grupos de dieta-Pó, apresentaram significante diminuição na espessura e volume trabecular quando comparado com os grupos de dieta-Pellet (GIV vs. GII, p<0,05; GIII vs. GI, p<0,01). Conclusão: Nossos resultados sugerem que a perda óssea mandibular foi resultado da diminuição da carga mecânica durante a mastigação, e a mandíbula não foi afetada pela supressão de estrogênio / Objectives: This study was designed to examine the effect of masticatory hypofunction and estrogen deficiency on mandible bone mass and compare this site with spine and femoral bone. Methods: Twenty-four rats were ovariectomized (OVX) or Sham-operated (Sham) and analyzed after feeding with hard-diet (Hard) or soft-diet (Soft). They were divided into 4 groups: (GI) Sham-Hard; (GII) OVX-Hard; (GIII) Sham-Soft and (GIV) OVX-Soft. Bone mineral density (BMD) was measured in the spine and femur in the baseline and at the end of the study, and BMD (final BMD baseline BMD) was calculated. In mandible bone, BMD and histomorphometry were analyzed at the end of the experiment. Results: Sham rats showed higher spine (GI: 13.5% vs. GII:0.74%, p<0.01; GIII:10.67% vs. GIV: - 4.36%, p<0.001) and femur BMD (GI:14.43% vs. GII:4.42%, p<0.01; GIII:10.58% vs. GIV:0.49%, p<0.001) than OVX but no difference was observed in mandible BMD among these groups (p>0.05). Soft-diet groups showed decreased mandible BMD compared with hard-diet groups (GIV vs. GII, p<0.01; GIII vs. GI, p<0.01). Similarly, mandibular condyle histomorphometry showed that soft-diet groups presented a significant decrease in trabecular thickness and volume (GIV vs. GII, p<0.05; GIII vs. GI, p<0.01) compared to hard-diet. Conclusions: Our results suggest that mandibular bone loss resulted from decreased mechanical loading during mastication, and was not affect by estrogen depletion

Objetivo: Examinar o efeito da hipofunção mastigatória e deficiência estrogênica no osso da mandíbula e comparar esta região com o osso da coluna e fêmur. Métodos: Vinte e quatro ratas Wistar foram ovariectomizadas (OVX) ou Sham-operadas (Sham) e analisadas após alimentação com dietanormal (Pellet) ou dieta-pó (Pó), divididas em 4 grupos: (GI) Sham-Pellet; (GII) OVX-Pelllet; (GIII) Sham-Pó; (GIV) OVX-Pó. A densidade mineral óssea (DMO) foi medida na coluna lombar e fêmur ao início e final do estudo, e a DMO (DMO inicial - DMO final) foi calculada. A DMO do osso mandibular e a histomorfometria foram analisadas ao final do experimento. Resultados: Os animais dos grupos Sham apresentaram DMO maior na coluna (GI:13.5% vs. GII:0.74%, p<0.01; GIII:10.67% vs. GIV:- 4.36%, p<0.001) e fêmur (GI:14.43% vs. GII:4.42%, p<0.01; GIII:10.58% vs. GIV:0.49%, p<0.001) que os dos grupos OVX, mas nenhuma diferença foi observada na DMO da mandíbula entre esses grupos (p>0,05). Por outro lado, os animais dos grupos de dieta-Pó mostraram diminuição da DMO da mandíbula quando comparados com os dos grupos de dieta-Pellet, (GIV vs. GII, p<0,01; GIII vs. GI, p<0,01). Semelhantemente, a análise histomorfométrica do côndilo mandibular mostrou que os grupos de dieta-Pó, apresentaram significante diminuição na espessura e volume trabecular quando comparado com os grupos de dieta-Pellet (GIV vs. GII, p<0,05; GIII vs. GI, p<0,01). Conclusão: Nossos resultados sugerem que a perda óssea mandibular foi resultado da diminuição da carga mecânica durante a mastigação, e a mandíbula não foi afetada pela supressão de estrogênio / Objectives: This study was designed to examine the effect of masticatory hypofunction and estrogen deficiency on mandible bone mass and compare this site with spine and femoral bone. Methods: Twenty-four rats were ovariectomized (OVX) or Sham-operated (Sham) and analyzed after feeding with hard-diet (Hard) or soft-diet (Soft). They were divided into 4 groups: (GI) Sham-Hard; (GII) OVX-Hard; (GIII) Sham-Soft and (GIV) OVX-Soft. Bone mineral density (BMD) was measured in the spine and femur in the baseline and at the end of the study, and BMD (final BMD baseline BMD) was calculated. In mandible bone, BMD and histomorphometry were analyzed at the end of the experiment. Results: Sham rats showed higher spine (GI: 13.5% vs. GII:0.74%, p<0.01; GIII:10.67% vs. GIV: - 4.36%, p<0.001) and femur BMD (GI:14.43% vs. GII:4.42%, p<0.01; GIII:10.58% vs. GIV:0.49%, p<0.001) than OVX but no difference was observed in mandible BMD among these groups (p>0.05). Soft-diet groups showed decreased mandible BMD compared with hard-diet groups (GIV vs. GII, p<0.01; GIII vs. GI, p<0.01). Similarly, mandibular condyle histomorphometry showed that soft-diet groups presented a significant decrease in trabecular thickness and volume (GIV vs. GII, p<0.05; GIII vs. GI, p<0.01) compared to hard-diet. Conclusions: Our results suggest that mandibular bone loss resulted from decreased mechanical loading during mastication, and was not affect by estrogen depletion

INTRODUÇÃO: A insuficiência cardíaca (IC) é uma síndrome sistêmica, cuja uma das possíveis evoluções se caracteriza pela perda de massa magra e intolerância aos esforços, quadro conhecido como caquexia cardíaca (CC). Estudos realizados usando homens e ratos demonstram que na associação da IC com hipogonadismo há um pior quadro clínico e desenvolvimento de CC, levando a um mal prognóstico e aumento da mortalidade. Para o sexo feminino, tanto no período pré ou pós-menopausa, não é conhecida a associação de possível deficiência de hormônios sexuais, tampouco seu impacto no prognóstico, mortalidade e desenvolvimento de CC em pacientes com IC. Os objetivos deste estudo foram: 1) Avaliar o efeito da IC sobre o possível desenvolvimento de CC em ratas. 2) Avaliar o efeito da IC sobre a produção de hormônios sexuais: Testosterona total, estradiol, FSH. MÉTODOS: Ratas da linhagem Sprague Dawley, com 60 dias de vida, foram divididas de acordo com os procedimentos cirúrgicos: Ratas intactas (INT) ou com ooforectomia (OVX), ratas com cirurgia fictícia (SHAM) do infarto do miocárdio (IM) ou cirurgia IM. A combinação destes procedimentos originou quatro grupos experimentais: INT+SHAM, INT+IM, OVX+SHAM e OVX+IM. Trinta dias após a OVX, amostras de sangue foram coletadas, para a dosagem hormonal e os animais foram submetidos à cirurgia de indução ao IM ou SHAM. Após oitos semanas, as ratas passaram pela avaliação ecocardiográfica. A partir desta, estabeleceu-se um corte de Fração de Ejeção (FE) <= 50% para definir o desenvolvimento de disfunção cardíaca a partir da realização do IM, constituindo dessa forma, os grupos INT+IM e OVX+IM. Com quatro semanas adicionais (totalizando 12 semanas após a indução do IM), houve a consolidação do quadro crônico de IC; então as ratas foram submetidas à avaliação hemodinâmica, da capacidade funcional e a nova coleta de sangue para dosagem hormonal. Após a eutanásia, os tecidos foram coletados para as análises morfológicas e histológicas. RESULTADOS: As ratas dos grupos OVX (OVX+SHAM e OVX+IM) não apresentaram ciclos ovarianos, demonstraram hipertrofia dos úteros e aumento do peso corporal final quando comparadas aos grupos INT (INT+SHAM e INT+IM), além de alterações na morfologia das glândulas adrenais - caracterizando o quadro de privação de hormônios ovarianos. As ratas dos grupos IM (INT+IM e OVX+IM) não tiveram alterações hemodinâmicas, contudo demonstraram reduzida capacidade funcional e piora nas variáveis ecocardiográficas (FE, FS, DSVE, TCIV) quando comparadas aos grupos SHAM (INT+SHAM e OVX+SHAM); as avaliações histológicas apontam valores de área infartada entorno de 40% e hipertrofia de septo nos grupos IM. Os animais não caracterizaram quadro de CC - caracterizada por diminuição do peso corporal, diminuição da densidade capilar na musculatura e atrofia das fibras musculares (m. sóleo) - após12 semanas de disfunção cardíaca / Introduction: Heart failure (HF) is a systemic disease, which one of the possible progress is characterized by lean mass loss and intolerance to efforts, this framework is known as cardiac cachexia (CC). Studies in men and rats have shown that when HF is associated with hypogonadism it has a worse clinical condition and CC evolution, leading to a poor prognosis and increased mortality. For females, both in the pre menopause period than in the post menopause it is not known how the association of sex hormones deficiency with HF can impact the prognosis and mortality of female patients, as well as the development of CC. The objectives of this study were: 1) Evaluate the effect of HF on the possible CC development in female rats. 2) Evaluate the effect of HF on the production of sex hormones: Total testosterone, estradiol, FSH. METHODS: Female rats (Sprague Dawley strain, 60 days old) were divided according to the surgical procedures: intact rats (INT) or ovariectomy (OVX) rats with sham surgery (SHAM) of myocardial infarction (MI) or MI surgery. The combination of these procedures led to four groups: INT + SHAM, INT + MI, OVX + SHAM and OVX + MI. 30 days after OVX, blood samples were collected for hormone dosage and the animals have been underwent to surgery to the MI induction or SHAM. After eight weeks, the rats have gone through echocardiographic evaluation. From this procedure, it was established a cutting Ejection Fraction (EF) <= 50% to define the development of cardiac dysfunction from the realization of MI, constituting INT + IM and IM + OVX groups. With four additional weeks (totaling 12 weeks after MI induction), there was the consolidation of HF\'s chronic condition; female rats were subjected to evaluation of functional and hemodynamic capacity and a new blood collection for hormonal dosage. After euthanasia, tissues were collected for morphological and histological analyzes. RESULTS: The rats of the OVX groups (OVX + SHAM and OVX + MI) showed no ovarian cycles, demonstrated uterus\' hypertrophy and an increase in final body weight when compared to INT groups (INT + SHAM and INT + MI), changes in morphology of the adrenal glands - evidencing the situation of ovarian hormones deprivation. The rats of the MI group (INT + MI and OVX + MI) had no hemodynamic changes, but showed reduced functional capacity and deterioration of echocardiographic variables (EF, FS, LVSD, IVCT) when compared to SHAM groups (INT + SHAM and OVX + SHAM ); the histological evaluations indicate infarcted area values around 40% and septal hypertrophy at MI groups. The animals did not characterize CC - characterized by decreased body weight, decreased capillary density in the muscle and muscle fiber atrophy (m. soleus) - even after 12 weeks of cardiac dysfunction

La ménopause est un facteur de risques associé au développement des maladies métaboliques. Du fait de ce déficit hormonal, les femmes ménopausées pourraient présenter des risques particuliers une fois exposées à des agents chimiques capables de perturber le système endocrinien. Pour en savoir plus, nous avons mis au point un modèle de souris ovariectomisées supplémentées ou non en œstradiol (E2), et exposées de manière chronique à un mélange de polluants (TCDD, PCB153, DEHP et BPA) ajoutés à une alimentation obésogène. Chaque polluant est utilisé à une dose équivalente à la Dose Journalière Tolérable, et l’exposition recouvre différents stades de développement, incluant ou non la période maternelle (gestation + lactation). Nos résultats indiquent qu’en condition d’obésité induite par le régime, l’ovariectomie accentue la prise de poids, l’intolérance au glucose et l’insulino-résistance chez les souris femelles adultes. Ce phénotype est associé à une diminution de la signalisation œstrogénique dans le foie et une dérégulation de l’adipogenèse et de l’inflammation dans le tissu adipeux. De manière intéressante, le mélange de polluants réduit l’impact délétère de l’ovariectomie sur le phénotype métabolique, possiblement par une amélioration de la signalisation œstrogénique dans le foie et le tissu adipeux. Nos résultats suggèrent fortement que ces effets dépendent d’une exposition maternelle. En conclusion, nous montrons que notre mélange de polluants possède une activité œstrogéno-mimétique. Ceci pourrait avoir une implication dans la compréhension du rôle des polluants environnementaux dans le développement des maladies métaboliques chez la femme en transition ménopausique / Menopause is a risk factor associated with the development of metabolic diseases. Because of estrogen deficiency, postmenopausal women may be at particular risk when exposed to chemical agents that can disrupt the endocrine system. To get more insight, we have developed a model of ovariectomized mice supplemented or not with estradiol (E2), and chronically exposed to a mixture of pollutants (TCDD, PCB153, DEHP and BPA) added to an obesogenic diet. Each pollutant was used at a dose close to the Tolerable Daily Intake dose, and the exposure had covered different stages of development, including or not the maternal period (gestation + lactation). Our results indicate that in diet-induced obesity, ovariectomy triggered weight gain, increase glucose intolerance and insulin resistance. This phenotype was associated with decreased estrogenic signaling in liver and deregulation of adipogenesis and inflammation in adipose tissues. Interestingly, the mixture of pollutants reduced the deleterious impact of ovariectomy on the metabolic phenotype, possibly through an alleviation of estrogenic signaling in both liver and adipose tissues. These data were not reproduced in mice not exposed to pollutants during the maternal life. In conclusion, the mixture of pollutants displayed some estrogeno-mimetic activity. This could have implications in understanding the role of environmental pollutants in the development of metabolic diseases in women in menopausal transition.

Στην παρούσα διατριβή, μελετήθηκε η επίδραση της ατορβαστατίνης στην εξέλιξη της οστεοπόρωσης. Ως πειραματικό μοντέλο επιλέχθηκε ο επίμυς, που, κατόπιν, απώλειας των οιστρογόνων λόγω ωοθηκεκτομής, αναπτύσσει οστεοπόρωση. Η επαγωγή της οστεοπόρωσης επιβεβαιώθηκε με πληθώρα μεθόδων. Αρχικά, (ημέρα 0) στο πειραματικό δείγμα (n=25) πραγματοποιήθηκαν μετρήσεις, στο αίμα, των βιοχημικών δεικτών του μεταβολισμού του οστού, (Αμινοτελικό πεπτίδιο του κολλαγόνου Τύπου Ι – NTx και οστεοκαλσίνη) με τη μέθοδο ELISA, μέτρηση της οστικής πυκνότητας με τη μέθοδο pQCT και αξιολόγηση της δομικής ακεραιότητας – ποιότητας του οστού με τη μέθοδο MDF. Ακολούθησε η αφαίρεση των ωοθηκών άμφω και, μετά από 60 ημέρες, επαναλήφθηκαν οι παραπάνω μετρήσεις. Όλες οι παραπάνω μέθοδοι, επιβεβαίωσαν την επαγωγή της οστεοπόρωσης μετά την ωοθηκεκτομή, και, άρα, την επιτυχία του πειραματικού μοντέλου. Αφού εξασφαλίσθηκε το οστεοπορωτικό μοντέλο, ο πειραματικός πληθυσμός χωρίστηκε τυχαία σε τρεις υπο-πληθυσμούς. Στον ένα υπο-πληθυσμό (n=10) χορηγήθηκε ατορβαστατίνη (4mg/kg/ημέρα), στον δεύτερο υπο-πληθυσμό (n=10) χορηγήθηκε αλενδρονάτη (4mg/kg/ημέρα), ενώ ο τρίτος υπο-πληθυσμός (n=5) χρησιμοποιήθηκε ως αρνητικός μάρτυρας και δεν έλαβε καμία θεραπεία (no-therapy control). Η χορήγηση των φαρμακευτικών αγωγών ήταν δια στόματος μέσω στοματογαστρικού καθετήρα και διήρκεσε από την ημέρα 60 έως την ημέρα 145. Μετά το πέρας χορήγησης των φαρμακευτικών αγωγών, επαναλήφθηκαν οι προαναφερθείσες μετρήσεις, τα πειραματόζωα θυσιάστηκαν και απομονώθηκαν οστά κνήμης για ιστολογική μελέτη, καθώς και μελέτη πρωτεϊνικών μορίων που εμπλέκονται στην κυτταρική βιολογία των κυττάρων του οστίτη ιστού. Συγκεκριμένα, η ιστολογική μελέτη συμπεριελάμβανε εκτίμηση των οστών με χρώση αιματοξυλίνης – ηωσίνης σε τομές παραφίνης, ιστομορφομετρία, ανοσοϊστοχημική χρώση των μορίων Bone Morphogenetic Protein-2 (BMP-2) και Fas (παράγοντας οστεοκλαστικής απόπτωσης) σε τομές σε πλαστικό, καθώς και ανοσοαποτύπωση κατά Western των αυτών πρωτεϊνών. Γενικά, όλες οι μέθοδοι που εφαρμόστηκαν, έδειξαν να ακολουθούν όλες τις μεταβολές στην δομική – ποιοτική κατάσταση των οστών, καθ’όλη την πειραματική πορεία. Ιδιάιτερη ευαισθησία στην ανίχνευση των μεταβολών αυτών, φάνηκε να παρουσιάζουν οι βιοχημικοί δείκτες του οστικού μεταβολισμού, αλλά και η νέα μέθοδος μέτρησης του Συντελεστή Εσωτερικής Απόσβεσης (MDF). Όσον αφορά στις φαρμακευτικές αγωγές, και η ατορβαστατίνη και η αλενδρονάτη παρουσίασαν θετική επίδραση στην εξέλιξη της οστεοπόρωσης, επιβραδύνοντάς την. Ειδικότερα, η ομάδα που έλαβε ατορβαστατίνη επέδειξε μια ισχυρότερη απόκριση στη χορήγηση της ουσίας, συγκριτικά με την ομάδα που έλαβε αλενδρονάτη. Προς την ίδια κατεύθυνση, φάνηκε να τείνουν και τα ευρήματα σχετικά με την έκφραση της BMP-2 και του Fas, αφού η ατορβαστατίνη ήταν η ουσία εκείνη που αύξησε την έκφραση και των δυο αυτών μορίων και, συνεπώς, την παραγωγή οστού από τους οστεοβλάστες και την απόπτωση των οστεοκλαστών. Στο σημείο αυτό θα ήταν σκόπιμο να σημειωθεί πως τα αποτελέσματα της μελέτης αυτής είναι ενδεικτικά και θα μπορούσαν να ισχυροποιηθούν με εφαρμογή των πειραματικών μεθόδων σε μεγαλύτερο πειραματικό δείγμα, μεγαλύτερη διάρκεια χορήγησης των φαρμάκων και δοκιμές διαφορετικών δόσεων αυτών. / The effects of the administration of atorvastatin on the development of ovariectomy-induced osteoporosis were evaluated in this study. The ovariectomized rat was employed as the experimental model. The development of osteoporosis, following ovariectomy was confirmed by a plethora of experimental methods and techniques. Initially (day 0), the experimental population (n=25) was submitted to blood measurements of the bone biochemical markers, NTx and osteocalcin (ELISA protocol), bone density measurements by pQCT and assessment of bone structural integrity with MDF methodology. MDF (Modal Damping Factor) is a new analytical and arithmetic method, based on the measurement of the dynamic characteristics of bone (quality factor and modal damping factor) by applying vibration excitation in the range of acoustic frequencies. Ovariectomy was performed to all test animals, and 60 days later, the same biochemical and radiological measurements were repeated. All the above methodologies confirmed the development of osteoporosis renderring, thus, the experimental animal model successful. Since osteoporosis had been confirmed, the experimental population was randomly divided (two cases to one control) into 3 sub-populations. The first sub-population (n=10) was administered atorvastatin (4mg/kg/day), the second sub-population (n=10) was administered alendronate (4mg/kg/day), whereas the third sub-population (n=5) was not administered any drug (no-therapy control). Drug administration was oral by gavage, from day 60 up to day 145. At the end of therapy, the test animals were again tested for levels of bone biochemical markers NTx and osteocalcin, and submitted to pQCT and MDF evaluation. They were, then, euthanized and tibiae were isolated for further histological studies. Specificly, histology studies included the evaluation of bone quality by eosin – hematoxylin staining of paraffin – embedded tibia sections, Histomorphometry, immunohistochemistry of methyl-methacrylate – embedded sections and Western Blotting for Bone Morphogenetic Protein-2 (BMP-2) and apoptotic factor Fas. In general, all methods applied followed the changes in bone integrity and quality, throughout the whole experimental course. Higher sensitivity in detecting these changes was exhibited by the bone biochemical markers and the new MDF method. With regard to the therapeutical agents administered, both atorvastatin and alendronate seemed to have a positive impact on the progression of osteoporosis, decelerating it. Especially, the atorvastatin – treated group presented a greated response to the administration of the drug, compared to the alendronate – treated one. The findings concerning the expression of BMP-2 and Fas, seemed to point to the same direction, since atorvastatin administration increased the levels of BMP-2 and Fas expression, increasing, thus, the bone production and osteoclast apoptosis, respectively. At this point, it would be wise to notice that our results are indicative, not conclusive and could be fortified by application of the methods used on a larger experimental sample size, longer administration of the drugs and tests of different drug dosages.

No description available.

No description available.