Search Results (59)

Background and Objective: This study presents a combined osteometric and biomechanical analysis of a Korean female cadaver exhibiting bilateral lower limb bone asymmetry with abnormal curvature and callus formation on the left femoral midshaft. Methods: To investigate bilateral bone length differences, osteometric measurements were conducted at standardized landmarks. Additionally, we developed three gait models using Meta Motivo, an open-source reinforcement learning platform, to analyze how skeletal asymmetry influences stride dynamics and directional control. Results: Detailed measurements revealed that the left lower limb bones were consistently shorter and narrower than their right counterparts. The calculated lower limb lengths showed a bilateral discrepancy ranging from 39 mm to 42 mm—specifically a 6 mm difference in the femur, 33 mm in the tibia, and 36 mm in the fibula. In the gait pattern analysis, the normal model exhibited a straight-line gait without lateral deviation. In contrast, the unbalanced, non-learned model demonstrated compensatory overuse and increased stride length of the left lower limb and a tendency to veer leftward. The unbalanced, learned model showed partial gait normalization, characterized by reduced limb dominance and improved right stride, although directional control remained compromised. Conclusions: This integrative approach highlights the biomechanical consequences of lower limb bone discrepancy and demonstrates the utility of virtual agent-based modeling in elucidating compensatory gait adaptations. Full article

Objectives: To employ artificial intelligence (AI) to automatically measure bone mineral density (BMD) and intramuscular fat in computed tomography (CT) images of patients with fractures and explore the association between these parameters and fracture healing. Methods: This retrospective study included patients who underwent baseline CT scans for rib fracture diagnosis and follow-up CT scans for fracture healing assessment at our hospital between 2012 and 2023. The volumetric BMD of the entire first lumbar vertebra (L1) and the paraspinal intramuscular fat area (PIFA) at the midsection of L1 in the baseline CT were extracted using AI. The primary outcomes, including callus formation, volume increase, and poor healing, and logistic regression were used to analyze the relationships between BMD and PIFA with primary outcomes. Results: Overall, 297 fractures from 53 patients (24 males; mean age: 53.83 ± 10.86 years) were included in this study. In multivariate regression analysis, a 1 standard deviation (SD) decrease in BMD was identified as an independent prognostic factor for reduced callus formation (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.50–0.97), diminished volume increase (OR = 0.70, 95% CI = 0.51–0.96), and elevated poor fracture healing at follow-up (OR = 2.08, 95% CI = 1.38–3.13). Similarly, a 1 SD increase in PIFA was an independent prognostic factor for reduced callus formation (OR = 0.24, 95% CI = 0.16–0.37), diminished volume increase (OR = 0.33, 95% CI = 0.23–0.49), and elevated poor fracture healing at follow-up (OR = 2.09, 95% CI = 1.50–2.93). Therefore, a model combining BMD, PIFA, and clinical characteristics significantly outperformed a model that included only clinical characteristics in predicting callus formation, volume increase, and poor fracture healing, with areas under the curve of 0.790, 0.749, and 0.701, respectively (all p < 0.001). Conclusions: BMD and PIFA can be used as early predictors of fracture healing outcomes and can help clinicians select appropriate interventions to prevent poor healing. Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that plays significant regulatory roles in the differentiation of the central nervous system and peripheral organs. A lack of the neuropeptide can lead to abnormalities in long bone development. In callus formation, a possible signaling balance shift in PACAP KO mice has been demonstrated, but Notch signalization, with its potential connection with PACAP 1-38, has not been investigated in ossification. Our main goal was to show connections between PACAP and Notch signaling in osteogenesis. Notch signalization showed an elevation in the long bones of PACAP-gene-deficient mice, and it was also elevated during the PACAP 1-38 treatment of UMR-106 and MC3T3-E1 osteogenic cells. Moreover, the inhibition of Notch signaling was compensated by the addition of PACAP 1-38 in vitro. The inorganic and organic matrix production of UMR-106 cells was increased during PACAP 1-38 treatment under the inhibition of Notch signaling. As a possible common target, the expression and nuclear translocation of NFATc1 transcription factor was increased during the disturbance of PACAP and Notch signaling. Our results indicate a possible synergistic regulation during bone formation by PACAP and Notch signalization. The crosstalk between Notch and PACAP signaling pathways highlights the complexity of bone development and homeostasis. Full article

Background: Delayed and failed fracture repair and bone healing remain significant public health issues. Dietary supplements serve as a safe, inexpensive, and non-surgical means to aid in different stages of fracture repair. Studies have shown that amorphous calcium carbonate (ACC) is absorbed 2 to 4.6 times more than crystalline calcium carbonate in humans. Objectives: In the present study, we assessed the efficacy of ACC on femoral fracture healing in a male Wistar rat model. Methods: Eighty male Wistar rats were randomly divided into five groups (n = six per group): sham, fracture + water, fracture + 0.5× (206 mg/kg) ACC, fracture + 1× ACC (412 mg/kg), and fracture + 1.5× (618 mg/kg) ACC, where ACC refers to the equivalent supplemental dose of ACC for humans. A 21-gauge needle was placed in the left femoral shaft, and we then waited for three weeks. After three weeks, the sham group of rats was left without fractures, while the remaining animals had their left mid-femur fractured with an impactor, followed by treatment with different doses of oral ACC for three weeks. Weight-bearing capacity, microcomputed tomography, and serum biomarkers were evaluated weekly. After three weeks, the rats were sacrificed, and their femur bones were isolated to conduct an evaluation of biomechanical strength and histological analysis. Results: Weight-bearing tests showed that treatment with ACC at all the tested doses led to a significant increase in weight-bearing capacity compared to the controls. In addition, microcomputed tomography and histological studies revealed that ACC treatment improved callus formation dose-dependently. Moreover, biomechanical strength was improved in a dose-dependent fashion in ACC-treated rats compared to the controls. In addition, supplementation with ACC significantly lowered bone formation and resorption marker levels two–three weeks post-fracture induction, indicating accelerated fracture recovery. Conclusions: Our preliminary data demonstrate that ACC supplementation improves fracture healing, with ACC-supplemented rats healing in a shorter time than control rats. Full article

Introduction: Clavicle fractures are among the most common in children, typically treated conservatively, with standard radiographs used to diagnose and monitor healing. Recently, infrared thermography (IRT) has been proposed as an alternative method for fracture detection, but no study has correlated the temperature changes during callus formation. Materials and Methods: Children aged 4–18 with X-ray-diagnosed clavicle fractures were included in the study. IRT measured temperatures above the fracture and contralateral healthy side on the 1st, 4th, 8th, 15th, and 22nd day after the injury. Along with IRT, an ultrasound was used to assess callus formation. Results: The study included 27 patients with an average age of 12.4 years, mostly boys. The left side was more often affected than the right side (33%). We found a correlation between callus formation and the ∆T. A maximum temperature difference of an average of 0.7 °C was noted during the proliferative phase of callus formation. After the formation of the fibrocartilaginous callus (4th to 8th day), the temperature above the fracture declined until it was equal (22nd day) to that of the healthy side. The average temperature difference between the broken and the healthy sides was statistically significant on the 4th and 8th days (during callus formation). Conclusions: The increased skin temperature above the fracture correlates with the inflammatory phase of bone healing. After the callus is visible on ultrasound, the temperature linearly drops with no statistical difference between the injured and the healthy sides. The standard protocol for clavicle fracture treatment typically involves using X-rays to assess callus formation during follow-up. IRT has shown potential in diagnosing callus formation in children with clavicle fractures, potentially reducing the need for traditional X-rays. Full article

Background and Objectives: Non-union is a severe complication of traumatic fracture that often leads to disability and decreased quality of life, with treatment remaining complex due to a lack of standardized protocols. This study examines the effectiveness of autologous conditioned serum (ACS) for non-union in patients who have a failed open reduction internal fixation (ORIF). Materials and Methods: Eleven patients with confirmed non-union at least 9 months post-ORIF or total hip replacement were enrolled. These patients received ACS treatment on the lesion sites once to three times monthly and were followed up. Efficacy was monitored through monthly X-rays to assess callus formation and bone union. Results: Seven patients received ACS three times, three patients received it twice, and the one who underwent total hip replacement received it once. Ten patients achieved union at the last follow-up visit, indicating the effectiveness of ACS in non-union cases unresponsive to ORIF. ACS demonstrated promising results in facilitating bone union in these challenging cases. Conclusions: ACS has the potential as an alternative or adjective treatment for non-union and is worthy of being investigated further for the benefits of patients. Full article

In reconstructive surgery following partial mandibulectomy, the biomechanical integrity of the fibula free flap applied to the remaining mandibular region directly influences the prognosis of the surgery. The purpose of this study is to evaluate the biomechanical integrity of two fixation materials [titanium (Ti) and hydroxyapatite/poly-L-lactide (HA-PLLA)]. In this study, we simulated the mechanical properties of miniplate and screw fixations in two different systems by finite element analysis. A three-dimensional mandibular model was constructed and a fibula free flap and reconstruction surface were designed. The anterior and posterior end of the free flap was positioned with two miniplates and two additional miniplates were applied to the angled area of the fibula. The masticatory loading was applied considering seven principal muscles. The peak von Mises stress (PVMS) distribution, size of fixation deformation, principal stresses on bones, and gap opening size were measured to evaluate the material properties of the fixation. In the evaluation of properties, superior results were observed with both fixation methods immediately after surgery. However, after the formation of callus between bone segments at 2 months, the performance of Ti fixation decreased over time and the differences between the two fixations became minimal by 6 months after surgery. The result of the study implies the positive clinical potential of the HA-PLLA fixation system applied in fibula free flap reconstruction. Full article

Stress shielding is a problem for traditional metal bone fixation plates made of magnesium and titanium alloys. This problem can be solved by using composite materials with a low elastic modulus. This study analyzed the effect of carbon fiber reinforced PEEK (CFRP) composites on stress shielding under static loading using finite element simulations. Callus formation times relative to the healing period were gradually imposed according to the elapsed time, considering 1% and 75% as healing stages. The Inventor© 3D CAD 2024 software was used for modeling, and the ANSYS© FEA R2023 software was used for analysis. The results showed that metal fixation plates made of titanium and magnesium alloys transferred less stress to the bone than the CFRP fixation plate. In particular, the use of the CFRP fixation plate resulted in a higher peak stress and a more uniform stress field in the bone, especially in the bone-plate contact area, where the risk of stress shielding is higher in the 1% and 75% healing phases. Full article

Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA. Full article

The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked plating technology enabled new strategies for the controlled dynamization of fractures, such as far cortical locking (FCL) screws or active plates with elastically suspended screw holes. However, these strategies did not allow for the use of non-locking screws, which are typically used to reduce bone fragments to the plate. This study documents the first in vivo study on the healing of ovine tibia osteotomies stabilized with an advanced active plate (AAP). This AAP allowed plate application using any combination of locking and non-locking screws to support a wide range of plate application techniques. At week 9 post-surgery, tibiae were harvested and tested in torsion to failure to assess the healing strength. The five tibiae stabilized with an AAP regained 54% of their native strength and failed by spiral fracture through a screw hole, which did not involve the healed osteotomy. In comparison, tibiae stabilized with a standard locking plate recovered 17% of their strength and sustained failure through the osteotomy. These results further support the stimulatory effect of controlled motion on fracture healing. As such, the controlled dynamization of locked plating constructs may hold the potential to reduce healing complications and may shorten the time to return to function. Integrating controlled dynamization into fracture plates that support a standard fixation technique may facilitate the clinical adoption of dynamic plating. Full article

Background: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5–10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers’ (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. Methods: A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. Results: A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients’ characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. Conclusions: Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union. Full article

The current reconstructive surgical procedures implemented after the resection of extended bone segments are associated with high complication rates and long-term treatments. By transplanting an autologous, vascularized and stabilized bone segment, these challenges can be managed. Thus, we propose a novel procedure to expand the currently available autologous bone grafts to the dimensions of the recipient bone using an implantable device. The objective of the present study was to characterize the feasibility of developing an implant prototype for fibula expansion in an in vitro model using a porcine fibula. A balloon catheter, as the part of the implant responsible for expansion, was proven to expand while being periodically filled with sodium chloride. Therefore, the expansion of the balloon catheter was analyzed in an experimental test setup with a 3D-printed porcine fibula with a closure film simulating callus formation to simulate the in vivo situation. Our experimental testing proved the successful expansion of the porcine fibula by the balloon catheter. Hence, the feasibility of the concept for subsequent animal testing was confirmed. Full article

Fracture callus formation is a dynamic stage of bone activity and repair with precise, spatially localized gene expression. Metastatic breast cancer impairs fracture healing by disrupting bone homeostasis and imparting an altered genomic profile. Previous sequencing techniques such as single-cell RNA and in situ hybridization are limited by missing spatial context and low throughput, respectively. We present a preliminary approach using the Visium CytAssist spatial transcriptomics platform to provide the first spatially intact characterization of genetic expression changes within an orthopedic model of impaired fracture healing. Tissue slides prepared from BALB/c mice with or without MDA-MB-231 metastatic breast cancer cells were used. Both unsupervised clustering and histology-based annotations were performed to identify the hard callus, soft callus, and interzone for differential gene expression between the wild-type and pathological fracture model. The spatial transcriptomics platform successfully localized validated genes of the hard (Dmp1, Sost) and soft callus (Acan, Col2a1). The fibrous interzone was identified as a region of extensive genomic heterogeneity. MDA-MB-231 samples demonstrated downregulation of the critical bone matrix and structural regulators that may explain the weakened bone structure of pathological fractures. Spatial transcriptomics may represent a valuable tool in orthopedic research by providing temporal and spatial context. Full article

The bone healing process is influenced by various physiological factors. Fracture fixation traditionally relied on rigid metallic implants. However, excessively rigid constructs can lead to complications, necessitating revision surgery. This review focuses on approaches to improve bone healing by introducing adequate interfragmentary movement (IFM) at the fracture site. IFM promotes secondary fracture healing and callus formation. Studies suggest that rigid fixation may impair fracture healing by inhibiting callus formation and causing stress shielding. Titanium alloy locking plates have been shown to be biomechanically superior to stainless steel. Flexible fixation and techniques to regulate implant stiffness are crucial for managing fractures with bridge plating. Materials with a lower Young’s modulus balance biomechanical properties. A novel TiNbSn alloy with a low Young’s modulus has been developed to address stress shielding issues. It is effective in promoting osteosynthesis, bone healing, and superior mechanical properties compared with materials with higher Young’s moduli. The enhanced formation of bone and callus associated with TiNbSn alloy suggests its promise for use in fracture treatment plates. Understanding the biomechanics of fracture healing, optimizing fixation stiffness, and exploring innovative materials like TiNbSn alloys, are crucial for advancing approaches to accelerate and enhance bone healing. Full article

Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced ‘angiogenic trauma response’. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies. Therefore, we herein analyzed in a stable closed femoral fracture model whether this compound also promotes fracture healing in aged mice. Forty-two aged CD-1 mice (age: 16–18 months) were daily treated with 30 mg/kg body weight cilostazol (n = 21) or vehicle (control, n = 21) by oral gavage. At 2 and 5 weeks after fracture, the femora were analyzed by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry, and Western blotting. These analyses revealed a significantly increased bending stiffness at 2 weeks (2.2 ± 0.4 vs. 4.3 ± 0.7 N/mm) and an enhanced bone formation at 5 weeks (4.4 ± 0.7 vs. 9.1 ± 0.7 mm³) in cilostazol-treated mice when compared to controls. This was associated with a higher number of newly formed CD31-positive microvessels (3.3 ± 0.9 vs. 5.5 ± 0.7 microvessels/HPF) as well as an elevated expression of phosphoinositide-3-kinase (PI3K) (3.6 ± 0.8 vs. 17.4 ± 5.5-pixel intensity × 10⁴) and runt-related transcription factor (RUNX)2 (6.4 ± 1.2 vs. 18.2 ± 2.7-pixel intensity × 10⁴) within the callus tissue. These findings indicate that cilostazol accelerates fracture healing in aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Hence, cilostazol may represent a promising compound to promote bone regeneration in geriatric patients. Full article