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Made available in DSpace on 2020-12-12T01:48:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) We sought to evaluate the effects of magnesium (Mg) intake deficiency on bone metabolism in rats with induced periodontal disease (PD). Holtzman rats were randomly divided into two groups: Control — animals fed a standard diet and test — animals fed a diet with 90% Mg deficiency. After 60 days on the diets, all animals received ligature on the lower left first molars to induce PD. Animals were euthanized after 30 days following ligature placement. Blood and urine were collected for determination of serum concentrations of Mg, calcium, osteocalcin (OCN), alkaline phosphatase and parathyroid hormone (PTH) by enzyme-linked immunosorbent assay, and the urinary concentration of deoxypyridinoline (DPD). Systemic bone mineral density (BMD), bone volume and architectural bone parameters were evaluated by micro-CT in L4 lumbar vertebrae and mandible. Tartrate-resistant acid phosphatase staining and immunohistochemical (IHC) analysis of inducible nitric oxide synthase (iNOS), Runt-related transcription factor 2 (RUNX2), CD86, CD80, proliferating cell nuclear antigen, vascular endothelial growth factor, OCN and osteopontin were investigated. Reverse-transcription polymerase chain reaction was employed to assess mRNA expression of receptor-activator of nuclear factor-kB ligand, osteoprotegerin (OPG) and interleukin (IL)-6. Mg deficiency was associated with higher concentrations of PTH and DPD, and significant decrease on both systemic and mandibular BMD, as well as greater severity of alveolar and trabecular bone loss. Significant increase in osteoclasts was observed in the test group with PD. IHC analysis showed significant increase in the expression of iNOS and decreased expression of OCN and RUNX2. Increased IL-6 mRNA and decreased OPG mRNA expressions were evidenced in the test group with PD. Mg deficiency caused systemic effects indicative of altered bone metabolism in the vertebrae and affected both immune and stromal cells, aggravating inflammatory bone resorption in the ligature-induced model of periodontitis. Department of Diagnosis and Surgery Sao Paulo State University School of Dentistry at Araraquara–UNESP Division of Diagnostic and Surgical Sciences UCLA School of Dentistry Molecular Biology Institute UCLA Department of Periodontology and Oral Implantology Dental Research Division Guarulhos University PhD Department of Morphology Sao Paulo State University School of Dentistry at Araraquara–UNESP Department of Diagnosis and Surgery Sao Paulo State University School of Dentistry at Araraquara–UNESP PhD Department of Morphology Sao Paulo State University School of Dentistry at Araraquara–UNESP FAPESP: 2006/05774-0 FAPESP: 2008/04855-2 FAPESP: 2015/21697-5 CAPES: AUXPE 655/2014

Made available in DSpace on 2018-12-11T17:22:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Objectives: The aim of this study was to investigate bone turnover alterations after alendronate (ALD) withdrawal and its influence on dental implants osseointegration. Materials and methods: Seventy female Wistar rats were randomly divided in 2 groups that received on day 0 either placebo (control group—CTL; n = 10) or 1 mg/kg sodium alendronate (ALD; n = 60) once a week for 4 months. At day 120, ALD treatment was suspended for 50 animals. Then, a titanium implant was placed in the left tibia of each rat that were randomly allocated in five subgroups of ten animals each, according to the period of evaluation: day 0 (INT-0), day 7 (INT-7), day 14 (INT-14), day 28 (INT-28), and day 45 (INT-45) after ALD withdrawal. CTL group and a group that received ALD until the end of the experimental period (non-interrupted group—non-INT; n = 10) underwent implant placement on day 120. Animals were euthanized 28 days after implant surgery. Bone mineral density (BMD) of femur and lumbar vertebrae were evaluated by DXA, biochemical markers of bone turnover were analyzed by ELISA, and bone histomorphometry was performed to measure bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). Results: All groups receiving ALD showed higher BMD values when compared to CTL group, which were maintained after its withdrawal. Decreased concentrations in all bone turnover markers were observed in the non-INT group, and in the groups in which ALD was discontinued compared to the CTL group. The non-INT group showed lower %BIC and notably changes in bone quality, which was persistent after drug withdrawal. Conclusion: Collectively, the findings of this study demonstrated that ALD therapy decreased bone turnover and impaired bone quality and quantity around dental implants, and that its discontinuation did not reverse these findings. Clinical relevance: The severe suppression of bone turnover caused by the prolonged use of ALD may alter the capacity of bone tissue to integrate with the implant threads impairing the osseointegration process. Department of Periodontics FAESA Dental School Department of Diagnosis and Surgery School of Dentistry at Araraquara Sao Paulo State University – UNESP, Humaita Street, 1680 Department of Periodontology and Oral Implantology Dental Research Division Guarulhos University Department of Physiology and Pathology School of Dentistry at Araraquara Sao Paulo State University – UNESP Department of Rheumatology School of Medicine University of São Paulo Division of Diagnostic and Surgical Sciences UCLA School of Dentistry Molecular Biology Institute UCLA Department of Diagnosis and Surgery School of Dentistry at Araraquara Sao Paulo State University – UNESP, Humaita Street, 1680 Department of Physiology and Pathology School of Dentistry at Araraquara Sao Paulo State University – UNESP

Periodontitis is an inflammatory disease that results from an interaction between dental biofilm agents and the host immune-inflammatory response. Periodontopathogenic organisms, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, as well as the host’s susceptibility, represented by the host’s genetic makeup, are the key factors that influence this complex disease. Recently, we identified haplotypes in the IL4 gene that were associated with chronic periodontitis (CP). This study aimed to evaluate whether subjects with different IL4 haplotypes (TCI/CCI and TTD/CTI) would be differentially colonized by periodontopathogens and whether they would respond differently to non-surgical periodontal therapy. Thirty-nine patients carrying the IL4 haplotype of genetic susceptibility to CP (IL4+) or protection against CP (IL4−) were evaluated. Those groups were further subdivided into individuals with CP (CP IL4+ or CP IL4−) and those that were periodontally healthy (H) (H IL4+ or H IL4−). CP patients were submitted to non-surgical periodontal therapy. Clinical and microbiological analyses were performed considering the data at baseline and 45 and 90 days after periodontal therapy. Periodontopathogens levels were evaluated by absolute quantitative polymerase chain reaction (qPCR). The baseline data revealed that the total levels of periodontopathogens were higher in the CP IL4+ than in the CP IL4− groups. Clinical analyses revealed that the periodontal therapy was equally effective, independent of the subject’s IL4 genetic load. The TCI/CCI IL4 haplotype, previously associated with genetic susceptibility to CP, was also associated with increased levels of periodontopathogenic bacteria, but this genetic background did not influence the response to non-surgical periodontal treatment.