Exogenous PTH 1-34 Attenuates Impaired Fracture Healing in Endogenous PTH Deficiency Mice via Activating Indian Hedgehog Signaling Pathway and Accelerating Endochondral Ossification

Fracture healing is a complicated, long-term, and multistage repair process. Intermittent administration of parathyroid hormone (PTH) has been proven effective on intramembranous and endochondral bone formation during the fracture healing process, however, the mechanism is unclear. In this study, we investigated the role of exogenous PTH and endogenous PTH deficiency in bone fracture healing and explored the mechanism by using PTH knockout (PTH-/-) mice and ATDC5 cells. In a mouse femur fracture model, endogenous PTH deficiency could delay endochondral ossification whereas exogenous PTH promotes accumulation of endochondral bone, accelerates cartilaginous callus conversion to bony callus, enhances maturity of bony callus, and attenuates impaired fracture healing resulting from endogenous PTH deficiency. In fracture callus tissue, endogenous PTH deficiency could inhibit chondrocyte proliferation and differentiation whereas exogenous PTH could activate the IHH signaling pathway to accelerate endochondral ossification and rescue impaired fracture healing resulting from endogenous PTH deficiency. In vitro, exogenous PTH promotes cell proliferation by activating IHH signaling pathway on ATDC5 cells. In mechanistic studies, by using ChIP and luciferase reporter assays, we showed that PTH could phosphorylate CREB, and subsequently bind to the promoter of IHH, causing the activation of IHH gene expression. Therefore, results from this study support the concept that exogenous PTH 1-34 attenuates impaired fracture healing in endogenous PTH deficiency mice via activating the IHH pathway and accelerating endochondral ossification. Hence, the investigation of the mechanism underlying the effects of PTH treatment on fracture repair might guide the exploration of effective therapeutic targets for fracture.

Association of Acute Perioperative Myocardial Injury With All-Cause Mortality Within 90 Days After Hip Fracture Repair in the Elderly: A Prospective Study

Introduction It remains unclear whether acute perioperative myocardial injury (APMI) increases mortality in the elderly. This study aimed to investigate APMI’s association with mortality within 90 days after hip fracture repair in elderly patients. Materials and Methods This prospective study enrolled elderly patients admitted to the department of Traumatology and Orthopaedics in XXX Hospital, who underwent surgery in 2018–2019 with a 90-day follow-up. According to survival status within 90 days, survival and death groups were constituted. Clinical, demographic, and laboratory indicators and 90-day mortality post-surgery were recorded. APMI’s association with 90-day mortality post-surgery was analyzed by logistic regression. Results Totally 248 participants were enrolled, including 224 and 24 in the survival and death groups, respectively, for a mortality rate of 9.7%. Compared with surviving individuals, the death group was older [81 (75–86) vs 87 (82–89) years], and had higher incidence rates of APMI (24.6% vs 58.3%), intertrochanteric fractures (41.1% vs 62.5%), preoperative atrial fibrillation (8.9% vs 29.2%), and dementia (73.7% vs 95.8%) (all P<.05). They also showed higher pre-injury frail scale scores [1 (0–2) vs 3 (1–4)] and Nottingham hip fracture scores (NHFSs) [4 (4–5) vs 6.5 (5–7)], lower Glomerular filtration [62 (46.1–78.6) vs 44.37 (35–61.92) ml/min], and reduced odds of glomerular filtration rate <60 mL/min (75.0% vs 46.9%) (all P < .05). APMI (OR = 3.294, 95% CI: 1.217–8.913) and NHFS (OR = 2.089, 95% CI: 1.353–3.225) independently predicted 90-day mortality post-surgery (all P<.05). Conclusions APMI is associated with increased mortality risk within 90 days after hip fracture repair in elderly patients.

The benefits of computed tomography imaging in the diagnosis, prognosis and treatment planning of equine orthopedic patients illustrated by six cases

Radiography and/or ultrasonography are the first imaging modalities for diagnosing orthopedic pathology in equine patients. However, in some cases, cross-sectional imaging is necessary to reach a more accurate diagnosis. Six cases were retrospectively selected from the imaging database of the Faculty of Veterinary Medicine (Ghent University) to illustrate the benefits of computed tomography (CT) in orthopedic patients. In two cases, CT demonstrated osteomyelitis lesions in two young foals, which could not be detected with radiography and ultrasonography. In three cases, CT was performed for surgical planning of fracture repair, and in one case CT demonstrated multiple lesions at the soft tissues and ligamentous insertions in the stifle. In all cases, CT revealed additional findings, which were important for the treatment and prognosis of the patient.

A Coupled Computational Framework for Bone Fracture Healing and Long-term Remodelling: Investigating the Role of Internal Fixation on Bone Fractures

In this study, a coupled computational modelling framework for bone fracture repair is presented that enables predictions of both healing and remodelling phases of the fracture region and is used to investigate the role of an internal fixation plate on the long-term healing performance of a fracture tibia under a range of different conditions. It was found that introduction of a titanium plate allowed the tibia to undergo successful healing at higher loading conditions and fracture gaps, compared to the non-plated versions. While these plated cases showed faster rates of repair in the healing phase, their performance was substantially different once they entered the remodelling phase, with substan-tial regions of stress shielding predicted. This framework is one of the few im-plementations of both fracture healing and remodelling phases of bone repair and includes several innovative approaches to smoothing, time-averaging and time incrementation in its implementation, thereby avoiding any unwanted abrupt changes between tissue phenotypes. This provides a better representa-tion of tissue development in the fracture site when compared to fracture healing models alone and provides a suitable platform to investigate the long-term performance of orthopaedic fixation devices. This would enable the more effective design of permanent fixation devices and optimisation of the spatial and temporal performance of bioabsorbable implants

ASA Physical Status Classification and Complications Following Facial Fracture Repair

Background: To investigate the association between American Society of Anesthesiologists (ASA) physical status classification and rates of postoperative complications in patients undergoing facial fracture repair. Methods: Patients were divided into 2 cohorts based on the ASA classification system: Class I/II and Class III/IV. Chi-square and Fisher’s exact tests were used for univariate analyses. Multivariate logistic regressions were used to assess the independent associations of covariates on postoperative complication rates. Results: A total of 3575 patients who underwent facial fracture repair with known ASA classification were identified. Class III/IV patients had higher rates of deep surgical site infection ( P = .012) as well as bleeding, readmission, reoperation, surgical, medical, and overall postoperative complications ( P < .001). Multivariate regression analysis found that Class III/IV was significantly associated with increased length of stay ( P < .001) and risk of overall complications ( P = .032). Specifically, ASA Class III/IV was associated with increased rates of deep surgical site infection ( P = .049), postoperative bleeding ( P = .036), and failure to wean off ventilator ( P = .027). Conclusions: Higher ASA class is associated with increased length of hospital stay and odds of deep surgical site infection, bleeding, and failure to wean off of ventilator following facial fracture repair. Surgeons should be aware of the increased risk for postoperative complications when performing facial fracture repair in patients with high ASA classification.

Numerical Simulation and Field Measurement Analysis of Fracture Evolution and Seepage Response of Key Aquiclude Strata in Backfill Mining

Solid waste backfill mining can effectively deal with gangue and other mining wastes, as well as control the movement and damage of rock strata. In this paper, the RFPA2D rock failure process analysis software is used to study the fracture evolution and seepage response mechanism of the key aquiclude strata (KAS) under the conditions of different structural characteristics, interlayer rock thickness, and backfilling ratios in backfill mining. The simulation results show that, in backfill mining, soft rock plays a crucial role in the fracture repair of KAS with different structural characteristics. An increase in the KAS thickness from 15 to 35 m is shown to results in a continuously improved repair of KAS fractures. At the advancing distance of the working face of 50~100 m and the KAS thickness of 35 m, the minimum vertical seepage velocity of 0.06 ‐ 0.78 × 10 − 2 m / s is reached. An increase in the backfilling ratio from 45 to 80% improves the control effect on the overlying strata. A case study of backfill mining in the Wugou Coal Mine located in the Anhui Province of China was conducted. At the goaf backfilling ratio of 80%, the composite KAS’s good control effect was achieved, which minimized seepage and avoided the water in rush phenomena. The above engineering application ensured the safe backfill mining of coal resources.

MAK122: A Novel Drug Utilizing Innovative Fracture Site Targeting Technology to Improve Bone Healing

Megakaryocytes play a pivotal role in the bone fracture healing process through enhancing osteoblast proliferation, osteoclastogenesis, and angiogenesis. Current fracture repair therapies require direct implantation during surgery (BMP-2, grafts etc.), which has limitations. In order to address this, a novel drug, compound MAK122, was created with targeting technology that directs its actions to the fracture site without needing to be implanted during surgery, limiting undesirable offsite effects, increasing the quantity of drug at the fracture site, and allowing for non-invasive treatment following assessment of the natural healing process. Therefore, this study examined the ability of MAK122 to stimulate megakaryocytes and subsequent bone healing. To accomplish this, male mice on a C57BL/6 background underwent a surgically induced femoral fracture. Following surgery, the mice were injected daily for the first 7 days with either saline (vehicle) or MAK122. Mice were then euthanized 2, 3 and 4 weeks post-surgery. Fracture healing was assessed by standard and novel methodologies. Biweekly X-rays were evaluated and bone union was scored showing that MAK122 accelerated bone healing compared to controls. Ex vivo µCT analysis demonstrated that MAK122 increased callus volume and the percentage of mineralized callus tissue compared to vehicle treatment. Biomechanical testing showed that MAK122 treatment resulted in stronger repairs as compared to vehicle treated controls with nearly a 2-fold increase in twist to failure and toughness parameters. Additionally, histological assessment demonstrated accelerated remodeling in MAK122 treated femurs compared to those treated with saline. Taken together, these pre-clinical data suggest that MAK122 is capable of promoting an environment in which megakaryocytes can favorably influence bone remodeling mechanisms, expediting fracture repair in murine models. Though further pharmacokinetic, pharmacodynamic, and toxicology studies are required, MAK122 displays potential to serve as a state-of-the-art therapy for improving fracture healing in humans.

Association Between Opioid Use and Diabetes in Patients With Ankle Fracture Repair

Background: Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to practicing clinicians. Ankle fracture patients with diabetes may experience prolonged healing, higher risk of hardware failure, an increased risk of wound dehiscence and infection, and higher pain scores pre- and postoperatively, compared to patients without diabetes. However, the duration of opioid use among this patient cohort has not been previously evaluated. The purpose of this study is to retrospectively compare the time span of opioid utilization between ankle fracture patients with and without diabetes mellitus. Methods: We conducted a retrospective cohort study using our institution’s TriNetX database. A total of 640 ankle fracture patients were included in the analysis, of whom 73 had diabetes. All dates of opioid use for each patient were extracted from the data set, including the first and last date of opioid prescription. Descriptive analysis and logistic regression models were employed to explore the differences in opioid use between patients with and without diabetes after ankle fracture repair. A 2-tailed P value of .05 was set as the threshold for statistical significance. Results: Logistic regression models revealed that patients with diabetes are less likely to stop using opioids within 90 days, or within 180 days, after repair compared to patients without diabetes. Female sex, neuropathy, and prefracture opioid use are also associated with prolonged opioid use after ankle fracture repair. Conclusion: In our study cohort, ankle fracture patients with diabetes were more likely to require prolonged opioid use after fracture repair. Level of Evidence: Level III, prognostic.