Mandibular disorders are among the most common birth defects in humans, yet the etiological factors are largely unknown. Most of the neonates affected by mandibular abnormalities have a sequence of secondary anomalies, including airway obstruction and feeding problems, that reduce the quality of life. In the event of lacking corrective surgeries, patients with mandibular congenital disorders suffer from additional lifelong problems such as sleep apnea and temporomandibular disorders, among others. The goal of this systematic review is to gather evidence on hormonal and genetic factors that are involved in signaling pathways and interactions that are potentially associated with the nonsyndromic mandibular disorders. We found that members of FGF and BMP pathways, including FGF8/10, FGFR2/3, BMP2/4/7, BMPR1A, ACVR1, and ACVR2A/B, have a prominent number of gene‐gene interactions among all identified genes in this review. Gene ontology of the 154 genes showed that the functional gene sets are involved in all aspects of cellular processes and organogenesis. Some of the genes identified by the genome‐wide association studies of common mandibular disorders are involved in skeletal formation and growth retardation based on animal models, suggesting a potential direct role as genetic risk factors in the common complex jaw disorders. Developmental Dynamics 248:162‐172, 2019. © 2018 Wiley Periodicals, Inc.

In patients greater than 50 years, the FRAX tool has modest predictive ability and could be used to aid in preventive treatment decision-making at the time of transplant.

BackgroundBone loss and fractures following hematopoietic stem cell transplantation (HSCT) is common,(1, 2) and identifying patients at high risk for osteoporotic fractures following HSCT remains challenging. In the general population, the World Health Organization fracture risk assessment tool - FRAX is utilized to estimate a patient's 10-year probability of developing a major osteoporotic fracture and hip fracture.(3) However, the utility of the FRAX model in predicting fractures following HSCT has not been evaluated.ObjectivesTo assess the predictive value of FRAX in osteoporotic fracture risk assessment following HSCT.MethodsWe conducted a retrospective cohort study of patients >18 years that received a HSCT at The University of Texas MD Anderson Cancer Center, from January 1, 2001 to December 31, 2010. Patients were considered to have entered the cohort at the time of HSCT. All patients were retrospectively followed until December 31, 2013 for assessment of osteoporotic fracture. Osteoporotic fractures following HSCT were identified using ICD-9 codes, and confirmed by radiology and physician documentation. FRAX probabilities were calculated from baseline information obtained by chart review.ResultsA total of 5,170 patients underwent a HSCT during the 10-year study period. During an average of 3.3 years of follow up, 10% of patients developed a fracture. Fracture rates were higher (14%) in patients that underwent an autologous HSCT in comparison to those that received an allogeneic HSCT (6%). Mean major osteoporotic fracture FRAX scores were significantly higher in individuals who sustained an osteoporotic fracture compared to individuals who did not. The area under the receiver operating characteristic curve at 5 and 10 years following the HSCT were 0.61 and 0.66 respectively (Figure). We assessed the ability of the FRAX model for prediction of osteoporotic fracture with and without considering death as a competing risk. The hazard ratios were similar for both models (HR, 2.63, 95% CI, 1.93, 3.59; HR, 2.54, 95% CI, 1.86, 3.47, respectively).Figure 1ConclusionsTo the best of our knowledge, this is the first study to demonstrate that the FRAX model has modest discriminative ability in predicting osteoporotic fractures following HSCT. Further independent validation of our findings is necessary, before routinely using the FRAX model in clinical practice.References Pundole XN, Barbo AG, Lin H, Champlin RE, Lu H. Increased incidence of fractures in recipients of hematopoietic stem-cell transplantation. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2015;33(12):1364–70.Schimmer AD, Minden MD, Keating A. Osteoporosis after blood and marrow transplantation: clinical aspects. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation. 2000;6(2A):175–81.Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporosis international: a journal...