Search

Post-mortem computed tomography (PMCT) is routinely used at many forensic institutions to guide the following autopsy and is especially useful for diagnosing fractures. This systematic review aims to investigate the sensitivity and specificity of a PMCT scan in fracture diagnosis of the hyoid-larynx complex (HLC) compared to traditional autopsy in cases involving traumatic neck injuries. We searched PubMed, SCOPUS and Web of Science and included papers with cases n ≥ 3 published between January 2000 and April 2023 reporting on PMCT and autopsy findings of fractures of the HLC. The search provided 259 results of which 10 were included. Overall sensitivity and specificity were 0.70 [0.59; 0.79] and 0.92 [0.80; 0.97] for hyoid bone fractures and 0.80 [0.62; 0.91] and 0.76 [0.63; 0.85] for the thyroid cartilage. The results show great variation, and a large range between studies. These results indicate that PMCT cannot replace autopsy in cases with HLC fractures. Future larger prospective studies are needed, examining fracture details, scan protocols and different slice thicknesses using uniform reporting., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Carpal navicular fractures are the most common carpal fractures. This study intends to explore the specific mechanism of Zoledronic Acid (ZA) in carpal navicular fracture healing via long non-coding RNA (lncRNA) growth arrest specificity 5 (GAS5) to mediate microRNA (miR)-29a-3p. A fractured rat model was constructed. Two weeks later, a subcutaneous injection of systemic ZA was implemented, and an injection of plasmid vectors interfered with GAS5 or miR-29a-3p expression was performed on the fracture site. Osteocalcin (OCN) and bone morphogenetic protein-2 (BMP-2) were determined, as well as serum levels of alkaline phosphatase (ALP), osteopontin (OPN) and osteoprotegerin (OPG) and bone mineral density. MC3T3-E1 cells were transfected with plasmid vectors interfering with GAS5 or miR-29a-3p, and cell proliferation and apoptosis were analyzed. GAS5 and miR-29a-3p expression in fractured rats was tested, together with their binding relationship. ZA promoted OCN and BMP-2 expression, increased bone mineral density and serum levels of ALP, OPN and OPG in fractured rats. GAS5 was upregulated and miR-29a-3p was down-regulated in fractured rats. Downregulation of GAS5 or upregulation of miR-29a-3p further promoted bone healing in fractured rats. GAS5 targets miR-29a-3p, and down-regulation of miR-29a-3p can reverse the effect of down-regulation of GAS5 on bone healing in fractured rats. ZA promoted the proliferation of MC3T3-E1 cells and inhibited apoptosis by regulating the GAS5/miR-29a-3p axis. ZA regulates miR-29a-3p expression by down-regulating GAS5 to promote carpal navicular fracture healing, promote MC3T3-E1 cell proliferation, and inhibit cell apoptosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Keel bone fractures (KBF) are one of the most important welfare problems in commercial laying hens. Despite extensive research on the matter, its etiology remains unclear. Studying fracture characteristics in radiographic images can aid in the understanding of the disorder. The aim of the current study was to provide detailed description of fracture characteristics and explore ossification in the keel bone. In this descriptive study, repeated cross-sectional sampling was performed in one commercial laying hen flock. The flock was visited at 11 time points from 17-57 weeks of age (WOA), radiographing 30 laying hens at each visit resulting in altogether 330 unique radiographs. Fracture characteristics and the keel bone's level of ossification were assessed in each radiograph. In total, 344 fractures were recorded, of which 71.5% were complete and 28.5% were incomplete. Of the complete fractures, 82.9% were recorded as transverse, and 15.9% as oblique. One comminuted and two butterfly fractures were recorded. The caudal third of the keel was the most common area for fractures. Fracture characteristics differed between the different regions of the keel bone; all incomplete fractures in the cranial third appeared on the ventral surface of the keel, whilst the majority of incomplete fractures on the caudal third appeared on the dorsal surface. This indicates that the underlying etiology might differ between the cranial and caudal part. Folding fractures were observed in 18.6% of all the fractures, and occurred in both cranial-, and caudal third of the keel, indicating possible underlying disorders of calcium metabolism. All hens at 32 WOA and older had a fully ossified keel, based on radiographic evaluation. Displacement and soft tissue swelling are common characteristics in fractures of traumatic origin. We found a high frequency of simple fractures, without these characteristics, indicating that non-traumatic causes may be of higher importance than conventional beliefs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gretarsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Musculoskeletal traumatic injuries (MTI) involve soft tissue lesions adjacent to a bone fracture leading to fibrous nonunion. The impact of MTI on the inflammatory response to fracture and on the immunomodulation of skeletal stem/progenitor cells (SSPCs) remains unknown. Here, we used single-nucleus transcriptomic analyses to describe the immune cell dynamics after bone fracture and identified distinct macrophage subsets with successive pro-inflammatory, pro-repair and anti-inflammatory profiles. Concurrently, SSPCs transition via a pro- and anti-inflammatory fibrogenic phase of differentiation prior to osteochondrogenic differentiation. In a preclinical MTI mouse model, the injury response of immune cells and SSPCs is disrupted leading to a prolonged pro-inflammatory phase and delayed resolution of inflammation. Macrophage depletion improves bone regeneration in MTI demonstrating macrophage involvement in fibrous nonunion. Finally, pharmacological inhibition of macrophages using the CSF1R inhibitor Pexidartinib ameliorates healing. These findings reveal the coordinated immune response of macrophages and skeletal stem/progenitor cells as a driver of bone healing and as a primary target for the treatment of trauma-associated fibrosis., (© 2024. The Author(s).)

Diabetes patients often suffer from fractures despite normal or high bone mineral density, a phenomenon known as the diabetic bone paradox. Gao et al. 1 identify AGEs as disrupting bone quality and compromising skeletal integrity in diabetic bone disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The periosteum contains skeletal stem/progenitor cells that contribute to bone fracture healing. However, the in vivo identity of periosteal skeletal stem cells (P-SSCs) remains unclear, and membrane protein markers of P-SSCs that facilitate tissue engineering are needed. Here, we identified integral membrane protein 2A (Itm2a) enriched in SSCs using single-cell transcriptomics. Itm2a+ P-SSCs displayed clonal multipotency and self-renewal and sat at the apex of their differentiation hierarchy. Lineage-tracing experiments showed that Itm2a selectively labeled the periosteum and that Itm2a+ cells were preferentially located in the outer fibrous layer of the periosteum. The Itm2a+ cells rarely expressed CD34 or Osx, but expressed periosteal markers such as Ctsk, CD51, PDGFRA, Sca1, and Gli1. Itm2a+ P-SSCs contributed to osteoblasts, chondrocytes, and marrow stromal cells upon injury. Genetic lineage tracing using dual recombinases showed that Itm2a and Prrx1 lineage cells generated spatially separated subsets of chondrocytes and osteoblasts during fracture healing. Bone morphogenetic protein 2 (Bmp2) deficiency or ablation of Itm2a+ P-SSCs resulted in defects in fracture healing. ITM2A+ P-SSCs were also present in the human periosteum. Thus, our study identified a membrane protein marker that labels P-SSCs, providing an attractive target for drug and cellular therapy for skeletal disorders.

Abstract: Fractures of the hyoid bone, particularly the greater horns, and thyroid cartilage (superior horns) are known to be associated with hanging deaths. Depending on the literature, the frequency of these fractures varies from 0% to 83%. The mechanism underlying these fractures is believed to be direct compression or indirect traction from the ligature. The relationship of these structures with the cervical spine cannot be visualized with traditional internal examination, due to obstruction by surrounding soft tissue. Postmortem computed tomography scan offers an unobscured view of the relationship of the laryngohyoid structures with the cervical spine.We aim to illustrate the phenomenon of displacement of the laryngohyoid structures associated with fractures of the horns. In our case reports, the laryngohyoid structures were displaced, not only superiorly and posteriorly, but also in 2 of the cases, by tilting, when the suspension point was at the posterior or posterolateral aspect of the neck. This displacement had caused the greater horns of the hyoid bone and superior horns of the thyroid cartilage to be approximated against the cervical spine, particularly the transverse processes. We believe that, in these circumstances, the fractures were caused by pressure of the horns of the laryngohyoid structures against the cervical spine., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

One step towards understanding bone fragility and degenerative diseases is to unravel the links between fracture resistance and the compositional and structural characteristics of cortical bone. In this study, we explore an optical method for automatic crack detection to generate full fracture resistance curves of cortical bone. We quantify fracture toughness, critical failure strains at the crack tip, and crack tortuosity in three directions and analyze how they relate to cortical bone microstructure. A three-point bending fracture test of single-edge notched beam specimens in three directions (cracks propagating transverse, radial and longitudinal to the microstructure) from bovine cortical bone was combined with 2D-digital image correlation. Crack growth was automatically monitored by analyzing discontinuities in the displacement field using phase congruency analysis. Fracture resistance was analyzed using J-R-curves and strains were quantified at the crack tip. Post-testing, a subset of specimens was scanned using micro-tomography to visualize cracks and to quantify their tortuosity. Both fracture toughness and crack tortuosity were significantly higher in the transverse direction compared to the other directions. Similar fracture toughness was found for radial and longitudinal directions, albeit 20% higher crack tortuosity in the radial specimens. This suggests that radial crack deflections are not as efficient toughening mechanisms. Strains at crack initiation were ∼0.4% for all tissue orientations, while at fully developed damage process zones failure strains were significantly higher in the transverse direction (∼1.5%). Altogether, we present unique quantitative data including different aspects of bone damage in three directions, illustrating the importance of cortical bone microstructure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Gustafsson reports financial support was provided by Swedish Research Council. Hanna Isaksson reports financial support was provided by Swedish Research Council. Anna Gustafsson reports financial support was provided by Royal Swedish Academy of Sciences. Anna Gustafsson reports financial support was provided by Crafoord Foundation. Anna Gustafsson reports financial support was provided by Foundation of Greta and Johan Kock. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The basis for increased fracture risk in type 2 diabetes (T2DM) is not well understood. In this multi-ethnic, population-based study (n = 565), we investigated bone microstructure, trabecular plate/rod morphology, and mineralization in women with T2DM (n = 175) with and without fracture using a second-generation HRpQCT and individual trabecula segmentation and mineralization (ITS; ITM). Covariate-adjusted aBMD was 3.0%-6.5% higher at all sites (all p<.005) in T2DM vs controls. By HRpQCT, T2DM had higher covariate-adjusted trabecular vBMD (5.3%-6.4%) and number (3.8%-5.1%) and greater cortical area at the radius and tibia. Covariate-adjusted cortical porosity was 10.0% higher at the tibia only in T2DM vs controls, but failure load did not differ. Among women with T2DM, those with adult atraumatic fracture (n = 59) had 5.2%-8.5% lower adjusted aBMD at all sites by DXA compared with those without fracture (n = 103). By HRpQCT, those with fracture had lower adjusted total vBMD and smaller cortical area (10.2%-16.1%), lower cortical thickness (10.5-15.8%) and lower cortical vBMD associated with 18.1 and 17.2% lower failure load at the radius and tibia, respectively (all p<.05); plate volume and thickness were 5.7% and 4.7% lower, respectively, (p<.05) while rod volume fraction was 12.8% higher in the fracture group at the tibia only. Sodium glucose cotransporter 2 inhibitor users (SGLT2i; n = 19), tended to have lower radial rod tissue mineral density by ITS (p=.06). GLP1 agonist users (n = 19) had trabecular deficits at both sites and higher cortical porosity and larger pores at the distal tibia. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits and fewer trabecular plates associated with lower failure load., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: The repair of bone after injury requires the participation of many different immune cell populations, which are derived from the hematopoietic lineage. The field of osteoimmunology, or the study of the interactions between bone and the immune system, is a growing field with emerging impact on both the basic science and clinical aspects of fracture healing., Recent Findings: Despite previous focus on the innate immune system in fracture healing, recent studies have revealed an important role for the adaptive immune system in bone repair. The composition of adaptive and innate immune cell populations present at the fracture site is significantly altered during aging and diet-induced obesity, which may contribute to delayed healing. Recent data also suggest a complicated relationship between fracture repair and systemic inflammation, raising the possibility that immune populations from distant sites such as the gut can impact the bone repair process., Summary: These findings have important implications for the treatment of fracture patients with antibiotics or anti-inflammatory drugs. Furthermore, the effects of systemic inflammation on fracture repair in the contexts of aging or obesity should be carefully interpreted, as they may not be uniformly detrimental., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties., (© 2024. The Japanese Society Bone and Mineral Research.)

Abstract: Fractures of bones are commonly encountered in traumatic injuries, and distinguishing between antemortem (AM) and postmortem (PM) bone fractures is crucial for estimating the time since injury and has important medicolegal implications. Correct differentiation enables understanding the dynamics of the injury and, in some cases, the cause of death. The present study aims to evaluate the gross morphological and histopathological characteristics of bony fracture surfaces to determine whether they occurred before or after an individual's death.Fifty-seven sets of bone samples, including both antemortem and artificially created postmortem fractures, were collected from cadavers during medicolegal autopsies, meeting the inclusion criteria. Gross morphological and histopathological features were examined after staining the bony fracture edges with hematoxylin and eosin stain. The study revealed distinct morphological characteristics at fracture surfaces for both antemortem and artificially created postmortem fractures. In addition, signs of vital reaction were observed exclusively in antemortem fracture cases.In conclusion, the findings emphasize the importance of meticulous morphological and histopathological examination of bony fracture surfaces to differentiate between antemortem fractures and artificially created postmortem artifacts. This differentiation holds significant value in forensic investigations and medicolegal cases., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Fractures of the hyoid bone (HB) and thyroid cartilage (TC) are important findings in emergency medicine and forensic pathology. This study aimed to determine the occurrence and anatomical localization of HB and TC fractures and to evaluate the etiological and risk factors.A total of 315 patients with HB and/or TC fractures were included over a 3-year period. Data regarding the incident type, cause of death, age, sex, body mass index, regional trauma findings, location of fractures, resuscitation, and toxicological analyses were collected. Injury severity scores were calculated using the Abbreviated Injury Scale.The study found that HB and TC fractures were associated with trauma severity. The hanging cases exhibited the highest number of fractures. A significant association was observed between neck trauma localization and HB and TC fractures. Fractures of the HB and TC horns were more commonly associated with neck trauma than fractures of the corpus. Hyoid bone and TC fractures can occur without direct trauma, emphasizing the importance of thorough examination and diagnosis, particularly after cardiopulmonary resuscitation.This study provides valuable insights into HB and TC fractures and contributes to the understanding and identification of these fractures in forensic autopsies and clinical settings., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Bone is regarded as one of few tissues that heals without fibrous scar. The outer layer of the periosteum is covered with fibrous tissue, whose function in bone formation is unknown. We herein developed a system to distinguish the fate of fibrous-layer periosteal cells (FL-PCs) from the skeletal stem/progenitor cells (SSPCs) in the cambium-layer periosteum and bone marrow in mice. We showed that FL-PCs did not participate in steady-state osteogenesis, but formed the main body of fibrocartilaginous callus during fracture healing. Moreover, FL-PCs invaded the cambium-layer periosteum and bone marrow after fracture, forming neo-SSPCs that continued to maintain the healed bones throughout adulthood. The FL-PC-derived neo-SSPCs expressed lower levels of osteogenic signature genes and displayed lower osteogenic differentiation activity than the preexisting SSPCs. Consistent with this, healed bones were thinner and formed more slowly than normal bones. Thus, the fibrous periosteum becomes the cellular origin of bones after fracture and alters bone properties permanently., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8 yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305 g/cm2 in femur neck BMD, 0.0075-0.0273 g/cm2 in femur troch BMD, 0.0173-0.0345 g/cm2 in LS BMD, and 0.0141-0.0339 g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65 yr., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in relation to fracture healing., Methods: A literature search was performed using the PubMed database. The quality of the articles was evaluated using critical appraisal checklists., Results: Thirty one studies were included in this review. These studies consistently support that neutrophils exert both beneficial and detrimental effects on bone regeneration, influenced by Tumor Necrosis Factor-α (TNF-α), Interleukin 8 (IL-8), mast cells, and macrophages. The N2 phenotype has recently emerged as one promoter of bone healing. The N1 phenotype has progressively been connected with inflammatory neutrophils during fracture healing., Conclusions: This review has pinpointed various aspects and mechanisms of neutrophil influence on bone healing. The recognition of N1 and N2 neutrophil phenotypes potentially shed new light on the dynamic shifts taking place within the Fracture Hematoma (FH)., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bone turnover and microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This exploratory study aimed to establish an initial understanding of microdamage accumulation and load to failure in healthy and osteolytic rat vertebrae following focal and systemic cancer treatment (docetaxel (DTX), stereotactic body radiotherapy (SBRT), or zoledronic acid (ZA)). Osteolytic spine metastases were developed in 6-week-old athymic female rats via intracardiac injection of HeLa human cervical cancer cells (day 0). Additional rats served as healthy controls. Rats were either untreated, received SBRT to the T10-L6 vertebrae on day 14 (15 Gy, two fractions), DTX on day 7 or 14, or ZA on day 7. Rats were euthanized on day 21. Tumor burden was assessed with bioluminescence images acquired on day 14 and 21, histology of the excised T11 and L5 vertebrae, and ex-vivo μCT images of the T13-L4. Microstructural parameters (bone volume/total volume, trabecular number, spacing, thickness, and bone mineral density) were measured from L2 vertebrae. Load to failure was measured with axial compressive loading of the L1-L3 motion segments. Microdamage accumulation was labeled in T13 vertebrae with BaSO 4 staining and was visualized with high resolution μCT imaging. Microdamage volume fraction was defined as the ratio of BaSO 4 to bone volume. DTX administered on day 7 reduced tumor growth significantly (p < 0.05). Microdamage accumulation was found to be increased by the presence of metastases but was reduced by all treatments with ZA showing the largest improvement in HeLa cell injected rats. Load to failure was decreased in untreated and SBRT HeLa cell injected rats compared to healthy controls (p < 0.01). There was a moderate negative correlation between load to failure and microdamage volume fraction in vertebrae from rats injected with HeLa cells (R = -0.35, p = 0.031). Strong correlations were also found between microstructural parameters and load to failure and microdamage accumulation. Several factors, including the presence of osteolytic lesions and use of cancer therapies, influence microdamage accumulation and load to failure in rat vertebrae. Understanding the impact of these treatments on fracture risk of metastatic vertebrae is important to improve management of patients with spinal metastases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Calcaneal tuberosity avulsion fracture, an extra-articular injury, is a rare fracture caused internally by Achilles tendon driven following intense contraction of gastrocnemius-soleus complex, and externally by low-energy (possibly high-energy). Moreover, the risk of injuries of the skin and Achilles tendon around calcaneal tuberosity is closely related to Lee classification and Carnero-Martín de Soto Classification of calcaneal tuberosity avulsion fracture. Although the diagnosis confirmed by X-ray, digital imaging and computed tomography (CT), magnetic resonance imaging (MRI) should also be used to evaluate soft tissue. In recent years, the understanding of this fracture has witnessed the development of different internal fixation devices and surgical procedures. These advances have been further elaborated scientifically in terms of their ability to provide stable fracture reduction ad resistance to Achilles tendon forces. In order to obtain a comprehensive knowledge of the disease, this article reviewed the new understanding of the anatomy, typing, risk factors, and treatment modalities of calcaneal tuberosity avulsion fracture in recent years., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships, (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Timing bone fractures is one of the main tasks of a forensic anthropologist, but still an uncertain diagnostic. In the literature, there are many macroscopic methods to distinguish perimortem from postmortem fractures, based on the distinct structural and mechanical properties of fresh and dry bones. However, this differentiation is still challenging, in particular when the bones are fragmented or still exhibit fresh properties. Although histologic analysis is often used as a complementary diagnostic tool in forensic pathology, its application in the evaluation of bone fractures is uncommon. The aim of this study was to investigate whether fractures of fresh bones reveal a distinct microcracking pattern compared to fractures of dry bones, in order to optimise the fracture timing. To this purpose, we histologically analysed perimortem and postmortem fractures in human humeri. The fresh bones were retrieved from traumatic autopsy cases, and the dry bones from donors which were experimentally fractured. Our results showed that the highest density and length of microcracks (MCKs) were found in the interstitial area of dry fractured bones, which may be considered a marker of postmortem damage. In fresh fractured bones, we generally observed a lower density of MCKs, but a higher proportion of osteonal MCKs, which may be considered a marker of perimortem trauma. In summary, the results of our exploratory study suggest that changes in intrinsic bone factors (mineral/organic components) result in a different microcracking pattern that can be used in fracture timing., (© 2022. The Author(s).)

Patellar fracture and dental anomaly syndrome (PADS) is a congenital bone disease of cats that is characterized by atraumatic bone fractures (most commonly the patella), the persistence of deciduous teeth, and impaction of permanent teeth. Jaw swelling due to osteomyelitis is often the reason that cats with PADS are presented for veterinary dental care. The clinical history, oral examination findings, dental radiological findings, and histopathology were evaluated for 13 cats with dental and skeletal pathology consistent with PADS, including 9 with osteomyelitis. Cats in this study were predominantly domestic shorthair (12 of 13 cats), and there was no apparent sex predilection. All cats had multiple persistent deciduous teeth and multiple impacted permanent teeth, although the number of persistent and impacted teeth varied. Osteomyelitis of the jaw typically occurred within the first 4 years of life. Osteomyelitis of the mandible was 4 times more common than osteomyelitis of the maxilla. Histologically, osteomyelitis was chronic, neutrophilic, and osteoproliferative. Necrotic bone was confirmed in 67% of osteomyelitis lesions. Histological evaluation of jaws without inflammation demonstrated abnormal amounts of unmodeled bone, abnormally dense bone, and retention of cartilage in the caudal mandible. Three cats in the study had mandibular distoclusion and 2 had concurrent paronychia. To obtain a favorable clinical outcome in PADS cats with jaw swelling, prompt and aggressive surgical treatment of osteomyelitis is required. Extraction of persistent deciduous teeth and impacted permanent teeth is recommended when there is associated periodontitis or osteomyelitis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Even though, proximal tibia is a common site of giant cell tumor and bone fractures, following tumor removal, nonetheless very little attention has been paid to affecting factors on the fracture risk. Here, nonlinear voxel-based finite element models based on computed tomography images were developed to predict bone fracture load with defects with different sizes, which were located in the medial, lateral, anterior, and posterior region of the proximal tibia. Critical defect size was identified using One-sample t-test to assess if the mean difference between the bone strength for a defect size was significantly different from the intact bone strength. Then, the defects larger than critical size were reconstructed with cement and the mechanics of the bone-cement interface (BCI) was investigated to find the regions prone to separation at BCI. A significant increase in fracture risk was observed for the defects larger than 20 mm, which were located in the medial, lateral and anterior regions, and defects larger than 25 mm for those located in the posterior region of the proximal tibia. Furthermore, it was found that the highest and lowest fracture risks were associated with defects located in the medial and posterior regions, respectively, highlighting the importance of selecting the initial location of a cortical window for tumor removal by the surgeon. The results of the BCI analysis showed that the location and size of the cement had a direct impact on the extent of damage and its distribution. Identification of critical regions susceptible to separation at BCI, can provide critical comments to surgeons in selecting the optimal cement augmentation technique, which may ultimately prevent unnecessary surgical intervention, such as using screws and pins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed to develop a deep learning (DL) algorithm for automated detection and localization of posterior ligamentous complex (PLC) injury in patients with acute thoracolumbar (TL) fracture on magnetic resonance imaging (MRI) and evaluate its diagnostic performance. In this retrospective multicenter study, using midline sagittal T2-weighted image with fracture (± PLC injury), a training dataset and internal and external validation sets of 300, 100, and 100 patients, were constructed with equal numbers of injured and normal PLCs. The DL algorithm was developed through two steps (Attention U-net and Inception-ResNet-V2). We evaluate the diagnostic performance for PLC injury between the DL algorithm and radiologists with different levels of experience. The area under the curves (AUCs) generated by the DL algorithm were 0.928, 0.916 for internal and external validations, and by two radiologists for observer performance test were 0.930, 0.830, respectively. Although no significant difference was found in diagnosing PLC injury between the DL algorithm and radiologists, the DL algorithm exhibited a trend of higher AUC than the radiology trainee. Notably, the radiology trainee's diagnostic performance significantly improved with DL algorithm assistance. Therefore, the DL algorithm exhibited high diagnostic performance in detecting PLC injuries in acute TL fractures., (© 2023. The Author(s).)

Purpose: The imaging diagnosis of fracture-related infection is often challenging. The aim of this study was to evaluate the value of 18 F-FDG PET/CT for the diagnosis of fracture-related infection (FRI) with internal fixation after orthopedic surgery in lower extremities., Methods: A total of 254 consecutive patients who underwent 18 F-FDG PET/CT scans with suspected FRI with internal fixation in lower extremities were retrospectively investigated 18 F-FDG PET/CT images were semiquantitatively evaluated with multiple metabolic parameters. Additionally, morphological information of the inguinal draining lymph nodes (DLN) with the highest SUV value was also collected and analyzed., Results: Patients were divided into two groups according to final diagnosis: the infected (N=197) and the non-infected group (N=57). The differences in the inguinal DLN-related parameters, including the long diameter, short diameter, maximum cross-sectional area, maximum standardized uptake value (SUVmax), metabolic volume (MV) 60%, MV70%, MV80%, total lesional glycolysis (TLG) 60%, TLG70%, TLG80%, and the infection suspected area related parameters, including SUVmax, MV25%, MV30%, MV35%, MV40%, MV50%, and TLG70%, between the two groups were statistically significant. We then compared the highest area under the curves (AUCs) among the morphological parameters of DLN, metabolic parameters of DLN, and metabolic parameters of the suspected infection area. The result demonstrated that SUVmax of the inguinal DLN showed the best diagnostic performance with an AUC of 0.939 ( P <0.05)., Conclusion: Semiquantitative analysis (especially SUVmax) of the inguinal DLN in 18 F-FDG PET/CT images could be a promising method for the diagnosis of suspected FRI with internal fixation after orthopedic surgery in lower extremities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Sun, Liang and Shen.)

Microstructural and compositional changes that occur due to aging, pathological conditions, or pharmacological treatments alter cortical bone fracture resistance. However, the relative importance of these changes to the fracture resistance of cortical bone has not been quantified in detail. In this technical note, we developed an integrated experimental-computational framework utilizing human femoral cortical bone biopsies to advance the understanding of how fracture resistance of cortical bone is modulated due to modifications in its microstructure and material properties. Four human biopsy samples from individuals with varying fragility fracture history and osteoporosis treatment status were converted to finite element models incorporating specimen-specific material properties and were analyzed using fracture mechanics-based modeling. The results showed that cement line density and osteonal volume had a significant effect on crack volume. The removal of cement lines substantially increased the crack volume in the osteons and interstitial bone, representing straight crack growth, compared to models with cement lines due to the lack of crack deflection in the models without cement lines. Crack volume in the osteons and interstitial bone increased when mean elastic modulus and ultimate strength increased and mean fracture toughness decreased. Crack volume in the osteons and interstitial bone was reduced when material property heterogeneity was incorporated in the models. Although both the microstructure and the heterogeneity of the material properties of the cortical bone independently increased the fracture toughness, the relative contribution of the microstructure was more significant. The integrated experimental-computational framework developed here can identify the most critical microscale features of cortical bone modulated by pathological processes or pharmacological treatments that drive changes in fracture resistance and improve our understanding of the relative influence of microstructure and material properties on fracture resistance of cortical bone., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic condition characterized by the disruption of blood supply to the femoral head, leading to ischemia of internal tissues, subchondral bone fractures, necrosis, and eventual collapse of the weight-bearing portion of the femoral head. This condition results in severe functional impairment, pain, and even disability of the hip joint. Existing animal models of ONFH have limitations in replicating the natural disease progression accurately. Thus, there is a critical need to develop a novel animal model capable of better simulating localized pressure on the human femoral head to facilitate ONFH-related research., Methods: In this study, we present a novel approach for modeling ONFH, which involves integrating stress factors into the modeling process through the utilization of 3D printing technology and principles of biomechanics. A total of 36 animals were randomly assigned to six groups, where they received either the novel modeling technique or the traditional hormone induction method. Subsequently, an 8-week treatment period was implemented, followed by conducting micro-CT scans and histological evaluations to assess tissue outcomes., Results: The study evaluated the cytotoxicity of the material used in the new model, and it was observed that the material did not exhibit any cytotoxic effects on cells. Additionally, the novel model successfully replicated the pathological features of ONFH, including femoral head collapse, along with a substantial presence of empty bone lacunae, cartilage defects, and subchondral bone fractures in the subchondral bone region., Conclusion: In conclusion, our study provides evidence that the new model shows the ability to simulate the progression of the disease, making it a valuable tool for research in this field and can contribute to the development of better treatment strategies for this debilitating condition. It holds great promise for advancing our understanding of the pathogenesis of ONFH and the potential therapeutic interventions for this challenging clinical problem., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Spine is the most common site for bone metastases. The evaluation of the mechanical competence and failure location in metastatic vertebrae is a biomechanical and clinical challenge. Little is known about the failure behaviour of vertebrae with metastatic lesions. The aim of this study was to use combined micro-Computed Tomography (microCT) and time-lapsed mechanical testing to reveal the failure location in metastatic vertebrae. Fifteen spine segments, each including a metastatic and a radiologically healthy vertebra, were tested in compression up to failure within a microCT. Volumetric strains were measured using Digital Volume Correlation. The images of undeformed and deformed specimens were overlapped to identify the failure location. Vertebrae with lytic metastases experienced the largest average compressive strains (median ± standard deviation: -8506 ± 4748microstrain), followed by the vertebrae with mixed metastases (-7035 ± 15605microstrain), the radiologically healthy vertebrae (-5743 ± 5697microstrain), and the vertebrae with blastic metastases (-3150 ± 4641microstrain). Strain peaks were localised within and nearby the lytic lesions or around the blastic tissue. Failure between the endplate and the metastasis was identified in vertebrae with lytic metastases, whereas failure localised around the metastasis in vertebrae with blastic lesions. This study showed for the first time the role of metastases on the vertebral internal deformations. While lytic lesions lead to failure of the metastatic vertebra, vertebrae with blastic metastases are more likely to induce failure in the adjacent vertebrae. Nevertheless, every metastatic lesion affects the vertebral deformation differently, making it essential to assess how the lesion affects the bone microstructure. These results suggest that the properties of the lesion (type, size, location within the vertebral body) should be considered when developing clinical tools to predict the risk of fracture in patients with metastatic lesions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Palanca reports financial support was provided by AOSpine International. Marco Palanca reports financial support was provided by European Commission Marie Sklodowska-Curie Actions. Enrico Dall'Ara reports financial support was provided by Engineering and Physical Sciences Research Council., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are known to disrupt the homeostasis of osteoblasts and osteoclasts. The purpose of this study was to identify the changes of osteoblasts and osteoclasts under long-term hyperglycaemic conditions, using a mouse fracture model of long-term hyperglycemia (LT-HG)., Methods: C57BL/6J mice and green fluorescent protein (GFP) -positive bone marrow transplanted C57BL/6J mice with LT-HG, maintained under a state of hyperglycaemia for 2 months, were used in this study. After the experimental fracture, we examined the immunohistochemical expression of proinsulin and tumor necrosis factor (TNF) -α at the fracture site. C57BL/6J fracture model mice without hyperglycaemia were used as controls., Results: In the LT-HG mice, chondrocyte resorption was delayed, and osteoblasts showed an irregular arrangement at the callus site. The osteoclasts were scattered with a decrement in the number of nuclei. The expression of proinsulin was confirmed in bone marrow derived cells (BMDCs) with neovascularization 2 and 3 weeks after fracture. Immunopositivity for TNF-α was also confirmed in immature chondrocytes and BMDCs with neovascularization at 2 weeks, and the number of positive cells was not decreased at 3 weeks. Examination of GFP-grafted hyperglycaemic mice showed that the majority of cells at the fracture site were GFP-positive. Immunohistochemistry showed that the rate of double positives was 15% for GFP and proinsulin and 47% for GFP and TNF-α., Conclusion: LT-HG induces an increase in the number of proinsulin and TNF-α positive cells derived from BMDCs. We suggest that proinsulin and TNF-α positive cells are involved in both bone formation and bone resorption after fracture under hyperglycaemic conditions, resulting in the delay of bone healing., (© 2023. The Author(s).)

This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral bisphosphonates for 1-16 years were obtained by bone biopsy. Samples were histologically processed and analyzed for bone area, microcrack number, and microcrack length. The analyses used statistical modeling and considered patient age, bone mineral density, bone volume/total volume, trabecular thickness, and bone turnover as potential covariates. Microcrack density (number of microcracks/total examined bone area) was linearly related (p = 0.018) to bisphosphonate treatment duration. None of the analyzed covariates contributed significantly to the observed relationship between microcrack density and bisphosphonate treatment duration. Observed increases in microcrack density with increasing bisphosphonate treatment duration is important because increasing levels of microcracks may not only affect bone remodeling but also reduce elastic modulus and are suspected to adversely affect other mechanical properties that may influence fracture risk. The present findings add to our prior results showing changes in bone material properties and modulus with bisphosphonate treatment duration and thereby provide a more comprehensive assessment of the relationship between bisphosphonate treatment duration and bone quality. Statement of Clinical Significance: The present findings provide information guiding clinical use of oral bisphosphonates for post-menopausal osteoporosis therapy., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Purpose: The radiographic interfacet angle (IFA), scaphoid facet inclination (SFI), and lunate facet inclination (LFI) of the distal radius were measured in patients with 3 distinct wrist pathologies to determine whether there is an association between these radiographic measurements and these conditions., Methods: Posteroanterior wrist radiographs were compiled from patients with 3 types of common wrist pathologies (scaphoid waist fracture [n = 54], scapholunate [SL] dissociation [n = 23], and dorsal ganglion [n = 51]). The patients were all Caucasians aged 20 to 45 years who met strict radiographic criteria. The IFA, SFI, and LFI values of these patients were compared with those obtained from 400 normal wrist radiographs of subjects who met the same selection criteria., Results: In men with a scaphoid waist fracture, the IFA and SFI were significantly greater than in normal men, whereas the LFI was significantly lower. In the SL dissociation group, for all patients and for subgroups stratified according to sex, the IFA and SFI were significantly lower than in the normal matched groups. In the dorsal ganglion group, differences were found in the IFA and SFI for women, but not for men., Conclusions: The facet orientations of the distal radius in patients with scaphoid fracture, SL dissociation, and dorsal ganglion differed from those in the normal population. The IFA alone is most likely to be associated with all 3 pathologies. The SFI and LFI are less likely to be associated with patients with carpal pathologies., Clinical Relevance: Patients with a greater IFA may be susceptible to scaphoid fractures when they fall on an overstretched hand. Patients with a smaller IFA may be susceptible to SL dissociation when they fall on an overstretched hand., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Keel bone fractures affect welfare, health, and production performance in laying hens. A total of one hundred and twenty 35-wk-old Hy-line Brown laying hens with normal keel (NK) bone were housed in furnished cages and studied for ten weeks to investigate the underlying mechanism of keel bone fractures. At 45 wk of age, the keel bone state of birds was assessed by palpation and X-ray, and laying hens were recognized as NK and fractured keel (FK) birds according to the presence or absence of fractures in keel bone. The serum samples of 10 NK and 10 FK birds were collected to determine bone metabolism-related indexes and slaughtered to collect keel bones for RNA-sequencing (RNA-seq), Micro-CT, and histopathological staining analyses. The results showed that the concentrations of Ca, phosphorus, calcitonin, 25-hydroxyvitamin D 3 , and osteocalcin and activities of alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP) in serum samples of FK birds were lower than those of NK birds (P < 0.05), but the concentrations of parathyroid hormone, osteoprotegerin, and corticosterone in serum samples of FK birds were higher than those of NK birds (P < 0.05). TRAP staining displayed that FK bone increased the number of osteoclasts (P < 0.05). Micro-CT analysis indicated that FK bone decreased bone mineral density (P < 0.05). Transcriptome sequencing analysis of NK and FK bones identified 214 differentially expressed genes (DEGs) (|log2FoldChange| > 1, P < 0.05), among which 88 were upregulated and 126 downregulated. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis indicated that 14 DEGs related to skeletal muscle movement and bone Ca transport (COL6A1, COL6A2, COL6A3, PDGFA, MYLK2, EGF, CAV3, ADRA1D, BDKRB1, CACNA1S, TNN, TNNC1, TNNC2, and RYR3) were enriched in focal adhesion and Ca signaling pathway, regulating bone quality. This study suggests that abnormal bone metabolism related to keel bone fractures is possibly responded to fracture healing in laying hens., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Finite element modelling methodologies available for assessing femurs with metastases accurately predict strength and pathological fracture risk which has led them to being considered for implementation into the clinic. However, the models available use varying material models, loading conditions, and critical thresholds. The aim of this study was to determine the agreement between finite element modelling methodologies in assessing fracture risk in proximal femurs with metastases., Methods: CT images of the proximal femur were obtained of 7 patients who presented with a pathologic femoral fracture (fracture group) and the contralateral femur of 11 patients scheduled for prophylactic surgery (non-fracture group). Fracture risk was predicted for each patient following three established finite modelling methodologies which have previously shown to accurately predict strength and determine fracture risk: non-linear isotropic -based model, strain fold ratio -based model, Hoffman failure criteria -based model., Findings: The methodologies demonstrated good diagnostic accuracy in assessing fracture risk (AUC = 0.77, 0.73, and 0.67). There was a stronger monotonic association between the non-linear isotropic and Hoffman -based models (τ = 0.74) than with the strain fold ratio model (τ = -0.24 and - 0.37). There was moderate or low agreement between methodologies in discriminating between individuals at high or low risk of fracture (κ = 0.20, 0.39, and 0.62)., Interpretation: The present results suggest there may be a lack of consistency in the management of pathological fractures in the proximal femur based on the finite element modelling methodologies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Compared to the documented overuse mechanisms of endplate fracture lesions, the cause of Schmorl's node injuries remains unknown, despite existing hypotheses. Therefore, this study aimed to examine and dissociate the overuse injury mechanisms of these spinal pathologies., Methods: Forty-eight porcine cervical spinal units were included. Spinal units were randomly assigned to groups that differed by initial condition (control, sham, chemical fragility, structural void) and loading posture (flexed, neutral). Chemical fragility and structural void groups involved a verified 49% reduction in localized infra-endplate trabecular bone strength and removal of central trabecular bone, respectively. All experimental groups were exposed to cyclic compression loading that was normalized to 30% of the predicted tolerance until failure occurred. The cycles to failure were examined using a general linear model and the distribution of injury types were examined using chi-squared statistics., Findings: The incidence of fracture lesions and Schmorl's nodes was 31(65%) and 17(35%), respectively. Schmorl's nodes were exclusive to chemical fragility and structural void groups and 88% occurred in the caudal joint endplate (p = 0.004). In contrast, 100% of control and sham spinal units sustained fracture lesions, with 100% occurring in the cranial joint endplate (p < 0.001). Spinal units tolerated 665 fewer cycles when cyclically loaded in flexed postures compared to neutral (p = 0.015). Furthermore, the chemical fragility and structural void groups tolerated 5318 fewer cycles compared to the control and sham groups (p < 0.001)., Interpretation: These findings demonstrate that Schmorl's node and fracture lesion injuries can result from pre-existing differences in the structural integrity of trabecular bone supporting the central endplate., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jack P. Callaghan reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Jack P. Callaghan reports financial support was provided by Canada Research Chairs., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

For some cases of canine appendicular osteosarcoma (OSA), limb-sparing treatment options are often desired, one of which is stereotactic body radiation therapy (SBRT). A major complication of SBRT is fracture of the irradiated bone at the site of treatment. The present study evaluated 127 appendicular OSA sites in 122 dogs treated with SBRT to identify the most common pathologic fracture locations and configurations. A total of 50 tumours experienced a pathologic fracture, and 38 had imaging sufficient to identify fracture configuration. The distal tibia was more likely to develop a fracture than other sites. Multiple types of fracture configuration (transverse, oblique, spiral and comminuted) were observed. The distal radius was significantly more likely to develop a transverse fracture than other sites. Documentation of fracture location and configuration leads to the identification of the forces contributing to fracture occurrence, since each configuration is a result of different forces acting on each affected bone. Such knowledge is imperative for the development of new approaches to diminish the occurrence of pathologic fractures., (© 2023 John Wiley & Sons Ltd.)

Background: The association of various morphological features of facet diastasis with posterior ligamentous complex (PLC) injury has not been previously described. This study aims to determine the diagnostic value of facet diastasis subtypes for diagnosing thoracolumbar PLC injury., Methods: We retrospectively reviewed 337 consecutive patients with acute thoracolumbar fractures who had computed tomography (CT) and magnetic resonance imaging (MRI) within 10 days of injury. Three and 5 reviewers evaluated MRI and CT images, respectively. Facet diastasis was subclassified as follows: Dislocated, no articular surface apposition; subluxed, incomplete articular surface apposition; and facet fracture articular process fractures which may be displaced ≥2 mm or otherwise undisplaced, facet joint widening (FJW) ≥ 3 mm. We examined the diagnostic accuracy and the multivariate associations of facet diastasis subtypes with PLC injury in MRI., Results: Facet dislocation, subluxation, and displaced facet fracture yielded a high positive predictive value (PPV) for PLC injury (96%, 88%, and 94%, respectively). In contrast, undisplaced facet fracture and FJW yielded a moderate PPV for PLC injury (78%, and 45%, respectively). Facet dislocation, subluxation, and displaced facet fracture showed independent associations with PLC injury (adjusted odds ratio [AOR] = 38.4, 17.1, 13.4, respectively; P < 0.05). Undisplaced facet fracture and FJW were not associated with PLC injury (AOR = 3.9 [95% confidence interval, 0.49-38.4], P = 0.20) and (AOR = 1.94 [95% confidence interval, 0.48-7.13]; P = 0.20; P = 0.33), respectively., Conclusions: Facet dislocation, subluxation, and displaced facet fracture, but not undisplaced facet fracture or FJW, were independently associated with PLC injury. Therefore, we propose to define facet diastasis as a surrogate marker of PLC injury in MRI based on these morphologies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome caused by heterozygous NF1 gene mutations. Patients with NF1 present with pleiotropic somatic secondary manifestations, including development of bone pseudarthrosis after fracture. Somatic NF1 gene mutations were reproducibly identified in patient-derived pseudarthrosis specimens, suggesting a local mosaic cell population including somatic pathologic cells. The somatic cellular pathogenesis of NF1 pseudarthroses remains unclear, though defects in osteogenesis have been posited. Here, we applied time-series single-cell RNA-sequencing (scRNA-seq) to patient-matched control and pseudarthrosis-derived primary bone stromal cells (BSCs). We show that osteogenic specification to an osteoblast progenitor cell population was evident for control bone-derived cells and haploinsufficient pseudarthrosis-derived cells. Similar results were observed for somatic patient fracture-derived NF1 -/- cells; however, expression of genetic pathways associated with skeletal mineralization were significantly reduced in NF1 -/- cells compared with fracture-derived NF1 +/- cells. In mice, we show that Nf1 expressed in bone marrow osteoprogenitors is required for the maintenance of the adult skeleton. Results from our study implicate impaired Clec11a-Itga11-Wnt signaling in the pathogenesis of NF1-associated skeletal disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Skeletal fractures are most common large-organ traumatic injuries that impact the functions and esthetic outcomes and quality of life. Unfortunately, infection during the fracture healing process and inadequate blood supply to the bone impede reduced ability to produce cartilage and effective bone callus formation, leading to nonunion or delayed union fracture. Therefore, studying the mechanism of fracture healing is an important task in solving the problem of fracture healing failure. Animal models of bone fracture healing are important tools to investigate the pathogenesis and develop treatment strategies. This protocol introduces researchers to a bone repair model utilizing the ribs of rats and the immunohistological expression of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) during the fracture healing processes., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

In forensic pathology, deaths due to mechanical injuries (blunt, sharp, and gunshot) require an autopsy in order to determine the cause and manner of death through a detailed examination of viscera, soft tissues, and the skeletal system. Sometimes, such as in cases of severe putrefaction, only the skeleton is observable. In such cases, the absence of bony defects does not mean that a trauma-related death should not be considered: yet, how often will a lethal mechanical death produce a defect in the skeletal system? The present study involved a retrospective review of autopsy reports to investigate the frequencies of soft tissue and related skeletal injuries in cases of violent deaths. A total of 200 autopsy reports for cases of four mechanisms of injury including sharp force trauma (n = 50), gunshot (n = 50), blunt force trauma (n = 50), and mechanical asphyxia (n = 50) were examined. Manner of death, localization of bone fractures, and correspondence between external injuries and bone fractures were reported. Frequencies of bone fractures and degree of correspondence with soft tissue injuries for each trauma group were evaluated. The result showed that lethal blunt trauma always caused bone fractures; 94.0% of violent deaths by gunshot involved bones; 48.0% of sharp force soft tissue injuries involved the bone tissue; and hyoid bone fractures were observed in 20.0% of cases of mechanical asphyxia., (© 2022 American Academy of Forensic Sciences.)

Purpose: To identify MRI findings for injuries to periarticular soft tissue structures that were related to isolated greater tubercle fracture., Materials and Methods: 16 patients (mean age: 53.8, range 30-71 yrs) were enrolled and diagnosed with isolated greater tubercle (GT) fracture with CT and MRI and underwent shoulder arthroscopy from September 2009 to April 2019. Two musculoskeletal radiologists were blinded to the patient history and arthroscopic surgical findings and reviewed patient's CT and MRI. Fracture displacement, fracture center, and presence of bony Bankart lesion with Hill sachs lesion were checked on shoulder CT. Soft tissue injuries, including rotator cuff injury, deltoid muscle injury, long head of biceps tendon injury, capsular injury, glenoid injury, and injury location of the subscapularis and infraspinatus were checked on shoulder MRI., Results: MRI showed supraspinatus injury (56.3%), subscapularis injury (56.3%), deltoid muscle injury (25%), infraspinatus injury (25%), teres minor muscle injury (37.5%), injury of the long head of the biceps tendon (43.8%), inferior glenohumeral ligament tear (87.5%), superior labral anterior-toposterior lesion (25%), Bankart lesion (18.8%), and Hill-Sachs lesion (6.3%). 88.9% of subscapularis injuries and 75% of infraspinatus injuries showed caudal predominance. All of the patients with infraspinatus injuries showed concomitant teres minor muscle injuries. In order of frequency, the fracture centers were anterior (25%), posterior (31.3%), and all (43.8%). For patients with Bankart and Hill- Sachs lesions, the fracture center included the posterior portion in all cases., Conclusion: MRI and active arthroscopic examinations may be valuable when an isolated GT avulsion fracture is identified on X-ray examination., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Medial proximal sesamoid bones (PSBs) from Thoroughbred racehorses that did (Case) or did not (Control) experience unilateral biaxial PSB fracture were evaluated for bone volume fraction (BVF), apparent mineral density (AMD), tissue mineral density (TMD), and microdamage in Case fractured, Case contralateral limb intact, and Control bones. A majority of Case bones had a subchondral lesion with high microdamage density, and low BVF, AMD, and TMD. Lesion microdamage and densitometric measures were associated with training history by robust linear regression. Exercise intensity was negatively related to BVF (0.07 ≤ R 2  ≤ 0.12) and positively related to microcrack areal density (0.21 ≤ R 2  ≤ 0.29) in the lesion; however, in an undamaged site, the relationships were opposite in direction. Regardless of location, TMD decreased with event frequency for both Case and Control, suggesting increased bone remodeling with exercise. Measures of how often animals were removed from active training (layups) predicted a decrease in TMD, AMD, BVF, and microdamage at regions away from the lesion site. A steady-state compartment model was used to organize the differences in the correlations between variables within the data set. The overall conclusions are that at the osteopenic lesion site, repair of microdamage by remodeling was not successful (e.g., lower bone mass, increased damage, and lower mineralization) but that in regions away from the lesion remodeling successfully controlled damage (e.g., higher bone mass, less microdamage, and lower mineralization)., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

In this retrospective study , we present the findings in 250 homicides by asphyxia in Denmark in a 25-year period, with a particular focus on the autopsy findings in strangulation. Our intention is for the results to be used in future death investigations, where difficulties in interpretation of findings in potential asphyxial deaths arise. Asphyxia homicides showed a strong bias with respect to sex, age, and homicide type. The frequent female victim was typically an adult, whereas the rarer male victim was most often a child. Female offenders most often killed their children, and male offenders most often killed their female partner. Generally, most asphyxia homicides took place in a domestic setting. Manual strangulation and ligature strangulation were the most common mechanisms of asphyxia homicides (81.6%). A lack of petechial hemorrhages, especially in the conjunctiva, was rare in homicidal strangulation, but there were exceptions, especially when there was postmortem decomposition, making it impossible to verify them. Most victims of strangulation had skin lesions in the face (including the jawline) or on the neck, with accompanying hemorrhages in muscle and connective tissue, but the findings could be subtle or compounded by decomposition. Fractures of the laryngo-hyoid complex were common in strangulation, particularly in manual strangulation (chi-sq = 4.0993, df = 1, P < 0.05) and were clearly related to the age of the victim (chi-sq = 82.193, df = 4, P < 0.001). In children and young adults dying from homicidal strangulation, a lack of fractures is to be expected, while a lack of fractures is unusual, but not entirely unexpected, for adults and aged people., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: There is little data available on non-operative treatment of anterior glenoid rim fractures (GRF). Nothing is known about fracture size and displacement in comparison to clinical outcomes and instability in a mainly middle-aged patient population. The aim of this study was to demonstrate the results of non-operative treatment in anterior glenoid rim fractures with the special focus on potential instability/recurrence., Methods: The inclusion criteria were non-operatively treated anterior GRF of at least ≥ 5 mm width using the age- and gender-matched Constant/Murley score (a.-/g.-CMS) and the Western Ontario Instability Index (WOSI). Radiographic parameters (fracture morphology, displacement, major tuberosity fractures and Hill-Sachs lesion using initial CT and radiographs) and the proportion of the fractured glenoid were detected (2D-CT-circle-method) and osteoarthritis (A.P. and axial radiographs) was classified according to Samilson/Prieto. Proportion of fractured glenoid and medial displacement were correlated with the recurrence rate and the clinical scores., Results: N = 36 patients could be followed-up after a mean of 4.4 years [12-140 month, average age: 58 (± 13, 33-86) years]. The a.-/g.-CMS was 93 (± 11, 61-100) points, and the WOSI was 81% (± 22%, 35-100%) on average. The mean intraarticular displacement was 4 mm (± 3 mm; 0-14 mm). The 2D-circle-method showed a mean glenoid fracture involvement of 21% (± 11, 10-52%). Two cases of frozen shoulders and one case with biceps pathology were associated with the trauma. Within the followed-up patient group re-instability has occurred in n = 2 patients (6%) within the first two weeks after trauma. Osteoarthritis was found in n = 11 cases. There was no correlation between the scores and the fracture size/displacement [(a.-/g.-CMS vs. displacement: r = - 0.08; p = 0.6; vs. size: r = - 0.29; p = 0.2); (WOSI vs. displacement: r = - 0.14; p = 0.4; vs. size: r = - 0.37; p = 0.06)], but very large (≥ 21%) fractures with displacement ≥ 4 mm showed slightly worse results without significant difference (a.-/g.-CMS p = 0.2; WOSI p = 0.2). The apprehension test was negative in all patients at final follow-up., Conclusion: Non-operative treatment of anterior GRF was associated with overall good results within a mainly middle-aged larger patient group. Re-instability is rare and is not associated with fragment size but can occur in the first weeks after trauma. Size and dislocation of the fracture is not a criterion for the prognosis of potential instability., Level of Evidence: Level IV, retrospective case series., (© 2021. The Author(s).)

Objective: To determine whether proximal sesamoid bone (PSB) microdamage and fracture toughness differ between Thoroughbred racehorses sustaining PSB fracture and controls., Study Design: Cadaveric case-control., Animals: Twenty-four Thoroughbred racehorses (n = 12 PSB fracture, n = 12 control)., Methods: Proximal sesamoid bones were dissected, and gross pathological changes and morphological measurements were documented. High-speed exercise history data were evaluated. Microdamage was assessed in fracture, fracture-contralateral limb (FXCL) and control PSBs using whole bone lead uranyl acetate (LUA) staining with micro-CT imaging or basic fuchsin histological analysis. Fracture toughness mechanical testing was carried out in 3-point-bending of microbeams created from PSB flexor cortices. Data were analyzed using ordinal logistic and linear regression models., Results: Microdamage was detected most commonly in the articular subchondral region of PSBs via LUA micro-CT and basic fuchsin histology. There were no differences in microdamage between FXCL and control PSBs. Fracture toughness values were similar for FXCL (1.31 MPa√m) and control (1.35 MPa√m) PSBs. Exercise histories were similar except that horses sustaining fracture spent a greater percentage of their careers in rest weeks., Conclusion: Microdamage was detected in the articular region of PSBs but was not greater in horses sustaining catastrophic PSB fracture. Fracture toughness of PSB flexor cortices did not differ between FXCL and control PSBs., Clinical Significance: Although uncommon, microdamage is localized to the articular region of Thoroughbred racehorse PSBs. Catastrophic PSB failure is not associated with lower PSB flexor cortex fracture toughness., (© 2022 American College of Veterinary Surgeons.)

Background: We hypothesized that old patients could increase skeletal muscle mass after fractures by exercise rehabilitation, even if they have a low initial muscle mass., Aim: This study aimed to evaluate the relationship between skeletal muscle mass and skeletal muscle changes in older patients after fractures., Methods: This case-control study took place in rehabilitation wards and included 807 patients aged ≥ 65 years with fractures. Patients were divided into two groups based on the skeletal muscle index (SMI) on admission by the sarcopenia cut-off points: low SMI group included patients with SMI < 7.0 for men and < 5.7 for women and high SMI group included patients with SMI ≥ 7.0 for men and ≥ 5.7 for women. Analysis of comparison between the two groups and multivariate logistic regression analyses were performed., Results: The SMI gain was significantly higher in the low SMI group (0.20) than in the high SMI group (0.00, p  < 0.001). There were also the differences in age, BMI, mini nutritional assessment short form, Charlson comorbidity index, length of hospital stay, and protein intake. The SMI on admission was significantly associated with increased SMI after rehabilitation (odds ratio 0.569, 95% confidence interval 0.455‒0.710). Length from onset to transfer to the hospital, hospital stay, and period of exercise therapy were also significantly associated with increased SMI., Conclusions: We found that older patients with low SMI after fracture gained more skeletal muscle mass than those with high SMI following exercise rehabilitation. In addition, SMI on admission was one of the factors independently associated with increased SMI., (© 2021. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Sagittal fractures of equine cheek teeth are commonly observed during oral examination. There are few reports on the apical and endodontic pathology associated with such fractures seen during computed tomographic (CT) examination., Objectives: This study aimed to document the prevalence of CT changes indicative of apical disease in equine cheek teeth, which have suffered a sagittal fracture involving the clinical ± reserve crown., Study Design: This study is a retrospective case series., Methods: CT examinations of equine heads with sagittal fractures of cheek teeth present were reviewed: 81 teeth from 49 horses were identified to have a sagittal cheek tooth fracture. The images were evaluated for apical pathology including gas (in the endodontic system and periapically), widened periodontal space, periapical sclerosis, apical clubbing, cementoma/hypercementosis, lamina dura loss, associated sinusitis and sinus mucosal swelling. An apical infection grading system was created to give each tooth a score. Hounsfield units were used to measure the density of the endodontic, apical and periapical regions. The fracture length ratio was recorded. Statistical analysis was performed using a generalised estimating equation to evaluate predictors of apical infection and associations between clinical signs and CT abnormalities., Results: Eighty-seven sagittal fractures (56 buccal, 17 palatal/lingual and 14 midline) from 81 teeth were recorded (74 maxillary and 7 mandibular). Apical infection was diagnosed in 73% (37/51, P = .05) of buccal, 55% (6/11, P = .07) of palatal/lingual, 100% (13/13) of midline, 100% (6/6) of multiple fractures and 96% (23/24, P = .008) of fractures involving infundibula. There was no significant relationship between apical infection and the presence of clinical signs associated with dental pathology (P = .4). There was no significant association between fracture length ratio and apical infection (P = 1.0). Midline sagittal fractures were significantly associated with sinusitis when compared with all other maxillary fractures (odds ratio [OR] 5.92, 95% confidence interval [CI] 1.67-20.83, P = .006). Loss of the lamina dura was not significantly associated with apical infection (P = .5)., Main Limitations: There is a maxillary cheek tooth bias in the data set and the subjective grading system., Conclusions: A large proportion of fractured cheek teeth have evidence of apical infection on CT examination and therefore warrant treatment., (© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Objective: To investigate the effects of fracture characteristics and concurrent subchondral bone pathology identified with computed tomography (CT) on the racing performance of Thoroughbred racehorses with fractures of the MC3/MT3 lateral condyle., Study Design: Retrospective cohort study., Sample Population: Thoroughbred racehorses (n = 50) with a fracture of the MC3/MT3 lateral condyle, which had preoperative CT and internal fixation performed., Methods: Medical records were reviewed for age, sex, limb, and surgical treatment. Computed tomography scans were evaluated to determine fracture characteristics including length, whether the fracture was incomplete or complete, and displacement. The presence of subchondral bone injury (SBI), sesamoid bone fracture, articular comminution, and fragmentation in the joint was noted. Racing data was obtained from an online database. Univariable and multivariable analyses determined associations between independent variables and outcomes., Results: Thirty-three (66%) horses raced after surgery. Horses with sesamoid bone fractures (P = .021), MC3/MT3 comminution (P = .016) and intra-articular fragmentation (P = .015) were less likely to race postoperatively. Concurrent SBI did not affect outcome. In the final multivariable model, sex (P = .015) and whether a fracture was incomplete or complete (P = .007) were the most significant predictors of racing postoperatively with females and horses with complete fractures being less likely to race., Conclusion: The prognosis for racing after a lateral condylar fracture is favorable but is decreased in horses with complete fractures and certain concurrent joint pathology., Clinical Significance: Horses presenting with lateral condylar fractures commonly have concurrent joint pathology. Computed tomography can aid in preoperative evaluation and prognostication by enabling more complete fracture assessment., (© 2022 American College of Veterinary Surgeons.)

The immune system is an active component of bone repair. Mast cells influence the recruitment of macrophages, osteoclasts and blood vessels into the repair tissue. We hypothesized that if mast cells and other immune cells are sensitized to recognize broken bone, they will mount an increased response to subsequent fractures that may be translated into enhanced healing. To test this, we created a bone defect on the left leg of anesthetized mice and 2 weeks later, a second one on the right leg. Bone repair in the right legs was then compared to control mice that underwent the creation of bilateral window bone defects at the same time. Mice were euthanized at 14 and 56 days. Mineralized tissue quantity and morphometric parameters were assessed using micro-CT and histology. The activity of osteoblasts, osteoclasts, vascular endothelial cells, mast cells, and macrophages was evaluated using histochemistry. Our main findings were (1) no significant differences in the amount of bone produced at 14- or 56 days post-operative between groups; (2) mice exposed to subsequent fractures showed significantly better bone morphometric parameters after 56 days post-operative; and (3) significant increases in the content of blood vessels, osteoclasts, and the number of macrophages in the subsequent fracture group. Our results provide strong evidence that a transient increase in the inflammatory state of a healing injury promotes faster bone remodelling and increased neo-angiogenesis. This phenomenon is also characterized by changes in mast cell and macrophage content that translate into more active recruitment of mesenchymal stromal cells., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)