Research Spotlight

Aminoshariae, A., Azarpazhooh, A., Diogenes, A. R., Fouad, A. F., Glickman, G. N., He, J., Kishen, A., Letra, A. M., Levin, L., Setzer, F. C., Tay, F. R. and Hargreaves, K. M. (2022). “Insights into the February 2022 Issue of the JOE.” J Endod 48(2): 141-143.

Full text of this article.

Welcome to the February 2022 issue of the JOE. Here, we share some of our favorite articles that are published in this issue of the Journal. We hope you look forward to reading these and other articles in the JOE

Wang, K., Xu, C., Xie, X., Jing, Y., Chen, P. J., Yadav, S., Wang, Z., Taylor, R. W., Wang, J. and Feng, J. Q. (2022). “Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force.” J Dent Res: 220345211062585.

Full text of this article.

Wnt-β-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt-β-catenin levels and Axin2(+) PDL progenitor cell numbers during OTM using immunostaining of β-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2(+) PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line (Axin2(CreERT2/+); R26R(tdTomato/+)). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2(Lin) PDL cells. Conversely, ablation of Axin2(+) PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2(+) PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. Future drug development targeting the Axin2(+) PDL progenitor cells may accelerate alveolar bone formation during orthodontic treatment.

Brennan, M. T., Madsen, L. S., Saunders, D. P., Napenas, J. J., McCreary, C., Ni Riordain, R., Pedersen, A. M. L., Fedele, S., Cook, R. J., Abdelsayed, R., Llopiz, M. T., Sankar, V., Ryan, K., Culton, D. A., Akhlef, Y., Castillo, F., Fernandez, I., Jurge, S., Kerr, A. R., McDuffie, C., McGaw, T., Mighell, A., Sollecito, T. P., Schlieve, T., Carrozzo, M., Papas, A., Bengtsson, T., Al-Hashimi, I., Burke, L., Burkhart, N. W., Culshaw, S., Desai, B., Hansen, J., Jensen, P., Menné, T., Patel, P. B., Thornhill, M., Treister, N. and Ruzicka, T. (2022). “Efficacy and safety of a novel mucoadhesive clobetasol patch for treatment of erosive oral lichen planus: A phase 2 randomized clinical trial.” J Oral Pathol Med 51(1): 86-97.

Full text of this article.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin(®) -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin(®) -CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-μg Rivelin(®) -CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin(®) -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

Meyer, Z. I., Polk, J. L., Zide, J. R., Kanaan, Y. and Riccio, A. I. (2022). “Lateral Cuneiform Ossification and Tibialis Anterior Tendon Width in Children Ages 3 to 6: Implications for Interference Screw Fixation of Tibialis Anterior Tendon Transfers in Children.” J Pediatr Orthop.

Full text of this article.

BACKGROUND: While the transfer of the tibialis anterior tendon (TAT) to the lateral cuneiform (LC) following serial casting has been used for nearly 60 years to treat relapsed clubfoot deformity, modern methods of tendon fixation remain largely unstudied. Interference screw fixation represents an alternative strategy that obviates concerns of plantar foot skin pressure-induced necrosis and proper tendon tensioning associated with button suspensory fixation. A better understanding of LC morphology in young children is a necessary first step in assessing the viability of this fixation technique. Therefore, the purpose of this investigation is to define LC morphology and TAT width in children aged 3 to 6 years. METHODS: A retrospective radiographic review of 40 healthy pediatric feet aged 3 to 6 years who had either magnetic resonance imaging or computed tomography scans was performed at a single pediatric hospital. The length, width, and height of only the ossified portion of the LC were measured digitally using sagittal, coronal, and axial imaging. In addition, the maximal cross-sectional diameter of the TAT was measured at the level of the tibiotalar joint. RESULTS: The average ossified LC width ranged from 8.5 mm in the 3-year-old cohort to 10.3 mm in 6-year-old children. Analysis of variance testing revealed no statistically significant difference in width between age groups. Average ossified LC length ranged from 13.5 mm in the 3-year-old cohort to 18.3 mm in 6-year-old children with statistically significant increases in age groups separated by 2 or more years. Significant differences in LC height, volume, and TAT diameter were demonstrated after analysis of variance testing. The TAT to ossified LC width ratio ranged from 44% to 53% across age groups. CONCLUSIONS: The dimensions of the LC ossification center are large enough to allow interference screw fixation in children 3 to 6 years of age. Further studies are needed to investigate interference screw fixation performance in the pediatric clubfoot population. LEVEL OF EVIDENCE: Level IV.

Bailey, L. C., Bryan, M., Maltenfort, M., Block, J. P., Teneralli, R., Lunsford, D., Boone-Heinonen, J., Eneli, I., Horgan, C. E., Lin, P. D., Reynolds, J. S., Solomonides, A. E., Janicke, D., Sturtevant, J. L., Toh, S., Taveras, E., Appelhans, B. M., Arterburn, D., Daley, M. F., Dempsey, A., Dugas, L. R., Finkelstein, J., Fitzpatrick, S. L., Goodman, A., Gurka, M. J., Heerman, W. J., Horberg, M., Hossain, M. J., Hsia, D. S., Isasi, C. R., Kharbanda, E. O., Messito, M. J., Murphy, K., O’Bryan, K., Peay, H. L., Prochaska, M. T., Puro, J., Rayas, M., Rosenman, M. B., Taylor, B., VanWormer, J. J., Willis, Z., Yeramaneni, S. and Forrest, C. B. (2022). “Antibiotics prior to age 2 years have limited association with preschool growth trajectory.” Int J Obes (Lond).

Full text of this article.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.