No abstract

ObjectivesDiabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM.MethodsClosed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint.ResultsMicroarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls.ConclusionsOur findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM.Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139–147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1.

Background: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression. There is increasing evidence that some miRNAs are involved in the pathology of diabetes mellitus (DM) and its complications. We hypothesized that the functions of certain miRNAs and the changes in their patterns of expression may contribute to the pathogenesis of impaired fractures due to DM. Methods: In this study, 108 male Sprague-Dawley rats were divided into DM and control groups. DM rats were created by a single intravenous injection of streptozotocin. Closed transverse femoral shaft fractures were created in both groups. On post-fracture days 5, 7, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was conducted with miRNA samples from each group on post-fracture days 5 and 11. The microarray findings were validated by real-time polymerase chain reaction (PCR) analysis at each time point. Results: Microarray analysis revealed that, on days 5 and 11, 368 and 207 miRNAs, respectively, were upregulated in the DM group, compared with the control group. The top four miRNAs on day 5 were miR-339-3p, miR451-5p, miR-532-5p, and miR-551b-3p. The top four miRNAs on day 11 were miR-221-3p, miR376a-3p, miR-379-3p, and miR-379-5p. Among these miRNAs, miR-221-3p, miR-339-3p, miR-376a-3p, miR-379-5p, and miR-451-5p were validated by real-time PCR analysis. Furthermore, PCR analysis revealed that these five miRNAs were differentially expressed with dynamic expression patterns during fracture healing in the DM group, compared with the control group. Conclusions: Our findings will aid in understanding the pathology of impaired fracture healing in DM and may support the development of molecular therapies using miRNAs for the treatment of impaired fracture healing in patients with DM.

Although the number of patients with osteoporosis is increasing worldwide, diagnosis and treatment are presently inadequate. In this study, we developed a deep learning model to predict bone mineral density (BMD) and T-score from chest X-rays, which are one of the most common, easily accessible, and low-cost medical imaging examination methods. The dataset used in this study contained patients who underwent dual-energy X-ray absorptiometry (DXA) and chest radiography at six hospitals between 2010 and 2021. We trained the deep learning model through ensemble learning of chest X-rays, age, and sex to predict BMD using regression and T-score for multiclass classification. We assessed the following two metrics to evaluate the performance of the deep learning model: (1) correlation between the predicted and true BMDs and (2) consistency in the T-score between the predicted class and true class. The correlation coefficients for BMD prediction were hip = 0.75 and lumbar spine = 0.63. The areas under the curves for the T-score predictions of normal, osteopenia, and osteoporosis diagnoses were 0.89, 0.70, and 0.84, respectively. These results suggest that the proposed deep learning model may be suitable for screening patients with osteoporosis by predicting BMD and T-score from chest X-rays.

A Morel-Lavallee lesion (MLL) involves posttraumatic fluid collection around the greater trochanter. Many cases of MLL are missed at the initial evaluation, and the treatment of MLL is not well established. We present two cases in which MLL was missed at the initial evaluation. Case 1. A 65-year-old man was run over by a parade float. There was subcutaneous hematoma around the left greater trochanter, and no fracture was found. We diagnosed this injury as MLL on the 7th day after the trauma. Although we performed percutaneous drainage, the injured area was infected. Case 2. A 57-year-old man was hit by a train in a factory. There was an iliac wing fracture, but an MLL was not initially recognized. On the 6th day after the trauma, when performing open reduction and internal fixation for the iliac fracture, we recognized the lesion and performed percutaneous drainage simultaneously. This lesion also became infected. In these two cases, the wounds finally healed after a long duration of treatment. We suggest that it is important to keep this injury in mind and debride the lesion early and completely in the treatment course.