Background: Micro‐computed tomography (micro‐CT) offers significant potential for identifying mineralized structures. However, three‐dimensional (3‐D) micro‐CT of alveolar bone has not been adapted readily for quantification. Moreover, conventional methods are not highly sensitive for analyzing bone loss or bone gain following periodontal disease or reconstructive therapy. The objective of this investigation was to develop a micro‐CT methodology for quantifying tooth‐supporting alveolar bone in 3‐D following experimental preclinical situations of periodontitis or reconstructive therapy.Methods: Experimental in vivo bone loss or regeneration situations were developed to validate the micro‐CT imaging techniques. Twenty mature Sprague‐Dawley rats were divided into two groups: bone loss (Porphyromonas gingivalis lipopolysaccharide‐mediated bone resorption) and regenerative therapy. Micro‐CT and software digitized specimens were reconstructed three‐dimensionally for linear and volumetric parameter assessment of alveolar bone (linear bone height, bone volume, bone volume fraction, bone mineral content, and bone mineral density). Intra‐ and interexaminer reproducibility and reliability were compared for methodology validation.Results: The results demonstrated high examiner reproducibility for linear and volumetric parameters with high intraclass correlation coefficient (ICC) and coefficient of variation (CV). The ICC showed that the methodology was highly reliable and reproducible (ICC >0.99; 9‐% confidence interval, 0.937 to 1.000; CV <1.5%), suggesting that 3‐D measurements may provide better alveolar bone analysis than conventional 2‐D methods.Conclusions: The developed methods allow for highly accurate and reproducible static measurements of tooth‐supporting alveolar bone following preclinical situations of bone destruction or regeneration. Future investigations should focus on using in vivo micro‐CT imaging for real‐time assessments of alveolar bone changes.

Stem cell therapy offers potential in the regeneration of craniofacial bone defects; however, it has not been studied clinically. Tissue repair cells (TRCs) isolated from bone marrow represent a mixed stem and progenitor population enriched in CD90- and CD14-positive cells. In this phase I/II, randomized, controlled feasibility trial, we investigated TRC cell therapy to reconstruct localized craniofacial bone defects. Twenty-four patients requiring localized reconstruction of jawbone defects participated in this longitudinal trial. For regenerative therapy, patients were randomized to receive either guided bone regeneration (GBR) or TRC transplantation. At 6 or 12 weeks following treatment, clinical and radiographic assessments of bone repair were performed. Bone biopsies were harvested and underwent quantitative micro-computed tomographic (μCT) and bone histomorphometric analyses. Oral implants were installed, subsequently restored, and functionally loaded with tooth restorations. Reconstructed sites were assessed for 1 year following therapy. No study-related, serious adverse events were reported. Following therapy, clinical, radiographic, tomographic, and histological measures demonstrated that TRC therapy accelerated alveolar bone regeneration compared to GBR therapy. Additionally, TRC treatment significantly reduced the need for secondary bone grafting at the time of oral implant placement with a fivefold decrease in implant bony dehiscence exposure (residual bone defects) as compared to GBR-treated sites ( p < 0.01). Transplantation of TRCs for treatment of alveolar bone defects appears safe and accelerates bone regeneration, enabling jawbone reconstruction with oral implants. The results from this trial support expanded studies of TRC therapy in the treatment of craniofacial deformities ( ClinicalTrials.gov number CT00755911).

Background: Prevention of alveolar bone destruction is a clinical challenge in periodontal disease treatment. The receptor activator of nuclear factor‐kappa B ligand (RANKL) inhibitor osteoprotegerin (OPG) inhibits osteoclastogenesis and suppresses bone resorption.Methods: To study the effects of RANKL inhibition on alveolar bone loss, an experimental ligature‐induced model of periodontitis was used. A total of 32 rats were administered human OPG‐Fc fusion protein (10 mg/kg) or vehicle by subcutaneous delivery twice weekly for 6 weeks. Negative or positive controls received no treatment or disease through vehicle delivery, respectively. Biopsies were harvested after 3 and 6 weeks, and mandibulae were evaluated by microcomputed tomography (μCT) and histology. Serum levels of human OPG‐Fc and tartrate‐resistant acid phosphatase‐‐b (TRAP‐5b) were measured throughout the study by enzyme‐linked immunosorbent assay (ELISA). Statistical analyses included analysis of variance (ANOVA) and Tukey tests.Results: Human OPG‐Fc was detected in the sera of OPG‐Fc–treated animals by 3 days and throughout the study. Serum TRAP‐‐b was sharply decreased by OPG‐Fc treatment soon after OPG‐Fc delivery and remained low for the observation period. Significant preservation of alveolar bone volume was observed among OPG‐Fc–treated animals compared to the controls at weeks 3 and 6 (P <0.05). Descriptive histology revealed that OPG‐Fc significantly suppressed osteoclast surface area at the alveolar crest.Conclusion: Systemic delivery of OPG‐Fc inhibits alveolar bone resorption in experimental periodontitis, suggesting that RANKL inhibition may represent an important therapeutic strategy for the prevention of progressive alveolar bone loss.