Unit:
Τομέας Υγείας - Μητέρας - ΠαιδιούLibrary of the School of Health Sciences
Dissertation committee:
Καθ. Περρέα Δ, Καθ. Γρηγορίου Ο, Αναπλ. Καθ. Σαλάκος Ν
Original Title:
Επίδραση των αναστολέων αρωματάσης, λετροζόλης και αναστραζόλης, στον οστικό μεταβολισμό και στο λιπιδαιμικό προφίλ θηλυκών επίμυων. Βιοχημική, ιστολογική και εμβιομηχανική μελέτη.
Summary:
Introduction: Aromatase inhibitors are widely used in the treatment of hormone
sensitive breast cancer in postmenopausal women. The purpose of this study was
to evaluate the strength of the bone by conducting a biomechanical study on the
femoral bones and to access the levels of bone turnover markers in
ovariectomized rats treated with anastrazole and letrozole. Α possible
association with metabolic and liver adverse effects also has been investigated.
Materials and methods: Fourty-five Wistar rats underwent ovariectomy and were
randomized in three groups in order to receive no treatment, anastrazole or
letrozole. At the time of the surgical procedure, two and four months after,
serum levels of OPG and RANKL were determined. At the end of the 4-month
period, ten control animals of similar age were added to the experiment. Serum
glucose, cholesterol, triglycerides, HDL-c and LDL-c were measured at baseline,
2 and 4 months. At the end of the experiment, all animals were euthanized and
the femoral bone was removed en block in order to perform the biomechanic
study. The applied force, the deflection of the central section, the maximum
load sustained by the bone specimen, the stiffness of the bone and the energy
absorbed until fracture, were measured. Livers were dissected immediately for
further histopathological analysis. The histological features were grouped into
4 broad categories: steatosis, ballooning, portal inflammation and lobular
activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter.
Results: At 4 months, total cholesterol differed among the OC and OL groups
(p=.005) and the control and OL groups (p=.011). HDL-C differed between the OC
and OL groups (p=.003) as well as between the OA and OL groups (p=.014). OC
group triglycerides, differed from those of the OL group (p=.005) and the
control group (p=.008). Similar results were observed in the case of OA group
(p=.039 when compared to OL group and p=.078 when compared to control group).
Two months after the initiation of the experimental protocol, differences were
observed in the mean levels of OPG and RANKL between control ovariectomized
rats and animals that were treated with anastrazole and letrozole,
Interestingly, these findings were not observed at the end of the experiment (4
months). On the other hand, the biomechanical study of the femoral bones
revealed a decreased value of stiffness among animals treated with aromatase
inhibitors as compared to their control counterparts. The liver pathology
analysis revealed significant differences among groups with favored mild
steatosis and ballooning among animals that received Anastrazole or Letrozole.
Conclusion: Anastrazole and Letrozole seem to negatively influence the lipid
profile in our experimental model. This information should be taken in caution
by medical oncologists when addressing patients with altered lipid metabolism.
Anastrazole and letrozole significantly affect bone metabolism and this effect
seems to directly correlate with the biomechanical properties of bones. Mild
histological liver alterations seem also to occur and these alterations should
be taken in mind in future clinical studies
Keywords:
Anastrazole, Letrozole, Breast cancer, Osteoporosis, Lipid profile
Number of references:
215
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