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Doxycycline (SDD) as a potential drug for osteopenic rats submitted to femoral implants

Grant number: 19/06628-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): October 31, 2020
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Vinícius Pedrazzi
Grantee:Bruna Scaf
Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Background: The loss of the dental element is still a very common fact, and may be due to trauma or bone disease. The restoration of the dental organ through implants has long been explored in the literature, but the great challenge of this type of clinical approach is its indication in bones affected by osteoporosis. It is known that when treatment with implants is indicated in patients with established osteoporosis, a longer postoperative time is expected and that there is a correlation between present osteoporosis and mandibular/maxillary traumas resulting from implant placement surgery. Objective: This study aims to compare the use of doxycycline in Wistar rats at subantimicrobial doses (SDD), which is a known divalent metal chelating agent (Calcium, for example) and a drug with known bone deposition, alendronate sodium, which is the standard medicine for the treatment of osteoporosis. In the treatment of rehabilitation by implants. Materials and Methods: To this end, 42 Wistar rats will be used in this project, divided into 6 groups (n = 7), the groups being defined as follows: C - Control; CDOX - Control exposed to doxycycline 30 mg/kg/day; CAL - Control exposed to sodium alendronate 0.7 mg/kg/week; OVX - Ovariectomized Control; OVXDOX - Ovariectomy exposed to doxycycline 30 mg/kg/day; OVXAL - Ovariectomy exposed to alendronate sodium 0.7 mg / kg / week. Rats, about 80 days old, will undergo the osteopenia induction procedure for 90 days. After this period, the rats will be treated with doxycycline at a dose of 30 mg/kg/ day or alendronate sodium at a dose of 0.7 mg/kg/week, both for 60 days. After 30 days of initiation of drug treatment, all animals will be submitted to implant placement in the femoral bones. After the other 30 days of the medicine, death will be induced. Samples of the right femur will be submitted to histological and histomorphometric analyzes of the bone-implant interface and immunohistochemical analysis by TRAP; while the left femora will undergo the biomechanical push-out test. Isolation of the mesenchymal cells from the femurs that will be differentiated into osteoblasts for analysis of cell metabolism will also be performed. The right and left tibiae will be excised for scanning electron microscopy with energy dispersive X-ray spectroscopy (EDS), bone densitometry, DNA Checkerboard, real time PCR and 3-point bending test. In addition, at the moment of induction of death, whole blood will be withdrawn to obtain the total serum that will be used for mineral analysis by atomic absorption spectrometer to visualize the amount of circulating calcium and titanium. Statistical analysis: The results of this project will be submitted to the multivariate linear model statistical test.

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