RESUMEN
The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin-neutralizing monoclonal antibody (Scl-Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl-Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature-induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl-Ab (+EP) or vehicle (+/- EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl-Ab to regenerate bone around tooth-supporting osseous defects. 3 and 6 wks after the initiation of Scl-Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro-computed tomography (micro-CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle + EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl-Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle + EP. After 6 weeks of treatment, BVF and TMD values in the Scl-Ab + EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl-Ab treatment groups. Scl-Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl-Ab therapy in this and other oral bone defect disease scenarios.
Asunto(s)
Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Proteínas Morfogenéticas Óseas/inmunología , Regeneración Ósea/efectos de los fármacos , Marcadores Genéticos/inmunología , Periodontitis/tratamiento farmacológico , Periodontitis/fisiopatología , Pérdida de Hueso Alveolar/sangre , Pérdida de Hueso Alveolar/complicaciones , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/efectos de los fármacos , Proceso Alveolar/patología , Animales , Biomarcadores/sangre , Imagenología Tridimensional , Inmunohistoquímica , Masculino , Periodontitis/sangre , Periodontitis/diagnóstico por imagen , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
BACKGROUND: Periodontal diagnosis relies heavily on traditional two-dimensional radiographic assessment. Despite efforts in improving reliability, current methods of detecting bone level changes over time or determining three-dimensional architecture of osseous defects are inadequate. To address these issues, computed tomography (CT) has been explored because of its ability to produce accurate three-dimensional imaging, but limitations such as radiation, machine size, and cost have made this approach impractical. Recently, cone beam computed tomography (CBCT) has turned this concept into potential reality because these lower-cost small machines produce high-quality data. Yet there is little research to establish periodontal bone measurement using CBCT as a valid method. Therefore, the aim of this study was to compare CBCT measurements of periodontal defects to traditional methods. METHODS: Artificial osseous defects were created on mandibles of dry skulls. CBCT scanning, periapical radiography (PA), and direct measurements using a periodontal probe were compared to an electronic caliper that was used as a standard reference. RESULTS: Linear measurements for all defects revealed no statistical differences between bone sounding, radiography, and CBCT. There was a significant difference when comparing isolated interproximal measurements using a probe versus the caliper (P<0.001) but no significant difference for CBCT or radiography. All bony defects were identifiable and measurable directly or with CBCT. In comparison, buccal and lingual defects could not be measured with radiographs. CONCLUSIONS: Overall, all three modalities are useful for identifying interproximal periodontal defects. Compared to radiographs, the three-dimensional capability of CBCT offers a significant advantage because all defects can be detected and quantified.