Major Bone Research Articles

Relationship between Osteoprotegrin and estrogen serum level with osteoporosis in postmenopausal Iraqi women

Abstract Osteoporosis can define as a major bone disease especially in older women, it correlated with decrease bone density and change in the bone structure that may be increase in bone fragility. Osteoporosis more prevalence in women with age over 50 years old (post menopause), this correlate with estrogen hormone deficiency, this bone loss may be rapid and lead to accelerate bone resorption because of lack of balance occur between osteoclast and osteoblast, increasing in the osteoblast differentiation lead to osteoporosis activation. After menopause estrogen level will decrease due to the lacking occur in eggs produced by ovaries and this will lead to increase synthesis of IL-1, IL-6 and tumor necrosis factor and OPG level will decreased and this will lead to increase bone turnover and osteoporosis, at the same time promote vascular calcification due to increase action of RANKL one bone and vascular cell. Two group included in this study divided into patient group (n=25), age 50 years and over postmenopausal women and control group (n=50), age between 30-50 years' premenopausal women. 5ml of blood was taken from both postmenopausal and premenopausal women. All blood samples for both groups was tested for calcium, alkaline phosphtase and OPG level. OPG level was determined by ELISA technique. Serum level of alkaline phosphatase was found to be higher in postmenopausal group than premenopausal women group (p<0.001). serum calcium level is lower in postmenopausal group than premenopausal women group (p<0.001). serum osteoprotegerin level was higher in postmenopausal group than premenopausal women group (p<0.001). osteoprotegerin (OPG) can be used as indicator of osteoporosis and useful for early diagnosis in postmenopausal women.

Autologous and Heterologous Minor and Major Bone Regeneration with Platelet-Derived Growth Factors.

This review aims to explore the clinical applications, biological mechanisms, and potential benefits of concentrated growth factors (CGFs), autologous materials, and xenografts in bone regeneration, particularly in dental treatments such as alveolar ridge preservation, mandibular osteonecrosis, and peri-implantitis. A systematic literature search was conducted using databases like PubMed, Scopus, and Web of Science, with keywords such as "bone regeneration" and "CGF" from 2014 to 2024. Only English-language clinical studies involving human subjects were included. A total of 10 studies were selected for qualitative analysis. Data were processed through multiple stages, including title and abstract screening and full-text evaluation. The findings of the reviewed studies underscore the potential of the CGF in enhancing bone regeneration through stimulating cell proliferation, angiogenesis, and extracellular matrix mineralization. Autologous materials have also demonstrated promising results due to their biocompatibility and capacity for seamless integration with natural bone tissue. When combined with xenografts, these materials show synergistic effects in improving bone quantity and quality, which are crucial for dental implant success. Future research should focus on direct comparisons of different techniques, the optimization of protocols, and broader applications beyond dental medicine. The integration of CGFs and autologous materials into routine clinical practice represents a significant advancement in regenerative dental medicine, with the potential for improved patient outcomes and satisfaction.

Plasma sTWEAK, diabetes mellitus, and bone fractures in postmenopausal women

BackgroundCytokines, such as tumor necrosis factor alpha (TNFα) and TNF-like weak inducer of apoptosis (TWEAK), may have pivotal roles in regulating bone remodeling in osteoporosis. Therefore, this study aims to investigate the potential association between plasma sTWEAK levels and bone fractures in diabetes mellitus (DM) and postmenopausal conditions. MethodsA nested case–control study was conducted within a cohort comprising 1057 postmenopausal women in Santa Maria. We analyzed 52 subjects who reported major bone fractures (defined as hip, forearm, humerus, or clinical vertebral fractures occurring after the age of 45 years, excluding high-impact fractures) and 110 subjects who did not experience fractures. Participants completed a questionnaire regarding clinical data, and anthropometric evaluations were conducted. Blood samples were collected for biochemical profiling, and sTWEAK plasma concentrations were determined via enzyme-linked immunosorbent assay (ELISA). Logarithmic transformation was applied to asymmetric variables. Student's t-test or Mann–Whitney test was utilized to compare data between two groups, while ANOVA or Chi-square test was employed for comparisons involving more than two groups. ResultsDiabetic subjects exhibited lower plasma levels of sTWEAK (p = 0.002). However, no significant differences were observed concerning the presence of bone fractures. ConclusionsPlasma levels of sTWEAK were not found to be associated with bone fragility in postmenopausal women. Nonetheless, reduced plasma levels of this cytokine were linked to diabetes mellitus.

TRATAMENTO CIRURGICO DE CERATOCISTOS ODONTOGÊNICOS: RELATO DE CASO CLÍNICO

Introduction: The keratocyst or keratocyst is an odontogenic tumor characterized as a lesion that affects the maxillary and mandibular regions. It is considered a benign lesion, reaching a prevalence of 3% to 11% among all odontogenic cysts, resulting in major bone loss. It can be asymptomatic and is usually diagnosed through routine radiographs or histopathological findings. Objective: To present a clinical case concerning the diagnosis and surgical treatment of an odontogenic keratocyst in the anterior mandibular region. Clinical case: Male, normosystemic, melanodermic patient. An increase in extraoral volume was observed on the right side of the face in the anterior region of the mandible. Panoramic radiography revealed well-defined, unilocular radiolucent images in the areas of the right lower first premolar, left lower third molar and bilateral upper third molars. On intraoral physical examination, bone bulging was observed in the region of the tooth in question. A computerized tomography scan was then requested, in which extensive expansive bone lesions were detected. Marsupialization and local decompression of the two upper lesions and the lower right lesion were performed, detecting the presence of liquid content. Firstly, an incisional biopsy was carried out and a decompression drain was installed in the three lesions. The histopathological report was of an odontogenic keratocyst. The decompression device remained in place for 30 days in the lower right lesion and approximately 15 days in the upper lesions, showing a significant reduction in the lesions. The lower right lesion was then enucleated. The 6-month post-operative image showed bone formation with no signs of recurrence. Conclusion: The proposed treatment proved to be effective in treating odontogenic keratocysts, but follow-up imaging is extremely important in view of the possibility of recurrence.

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

A pH-Responsive Ti-Based Local Drug Delivery System for Osteosarcoma Therapy.

Osteosarcoma is one of the major bone cancers, especially for youngsters. The current treatment usually requires systemic chemotherapy and the removal of bone tumors. Titanium (Ti)-based implants can be modified as local drug delivery (LDD) systems for controllable and localized chemotherapeutic drug release. In this work, a pH-responsive Ti-based LDD prototype was designed by introducing polydopamine (PDA) to release doxorubicin (DOX) around osteosarcoma cells with low pH. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a contact angle meter were applied for surface characterization. Both direct and indirect cell culture modes were performed for biocompatibility and biofunction assessments. The results indicate that the Ti-based LDD prototype exhibits significant pH-dependent DOX release. The cumulative release can reach up to approximately 40% at pH = 6.0 after 72 h, but only around 20% at pH = 7.4. The Ti-based LDD implant shows good biocompatibility with approximately 93% viability of MC3T3 cells after direct culture in vitro for 24 h. Both direct and indirect culture modes verify the good anti-osteosarcoma function of the LDD implant, which should be attributed to the pH-responsive release of DOX.

Bone development by Hedgehog and Wnt signaling, Runx2, and Sp7.

Hedgehog and canonical Wnt signaling pathways and the transcription factors Runx2 and Sp7 are essential for osteoblast differentiation. Ihh is necessary for the commitment of perichondrial mesenchymal cells to Runx2+ osteoprogenitors and for the formation of the bone collar and primary spongiosa. Runx2 is needed for osteoblast differentiation during both endochondral and intramembranous ossification. It regulates the commitment of mesenchymal cells to osteoblast-lineage cells and their proliferation by inducing the expression of Hedgehog, Fgf, Wnt, Pthlh signaling pathway genes, and Dlx5. The Runx2-induced expression of Fgfr2 and Fgfr3 is important for the proliferation of osteoblast-lineage cells. Runx2 induces Sp7 expression and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Runx2, Sp7, and canonical Wnt signaling induce the differentiation of preosteoblasts into osteoblasts. Canonical Wnt signaling, but not Sp7, enhances the proliferation of osteoblast-lineage cells. In mature osteoblasts, Runx2 plays an important role in the expression of major bone matrix protein genes, including Col1a1, Col1a2, Spp1, Ibsp, and Bglap/Bglap2. The canonical Wnt signaling pathway is also crucial for bone formation by mature osteoblasts. Sp7 is needed for osteocytes to acquire a sufficient number of processes and a reduction in these processes results in osteocyte apoptosis and cortical porosity.

Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.

Runx2 (runt related transcription factor 2) and Sp7 (Sp7 transcription factor 7) are crucial transcription factors for bone development. The cotranscription factor Cbfb (core binding factor beta), which enhances the DNA-binding capacity of Runx2 and stabilizes the Runx2 protein, is necessary for bone development. Runx2 is essential for chondrocyte maturation, and Sp7 is partly involved. Runx2 induces the commitment of multipotent mesenchymal cells to osteoblast lineage cells and enhances the proliferation of osteoprogenitors. Reciprocal regulation between Runx2 and the Hedgehog, fibroblast growth factor (Fgf), Wnt, and parathyroid hormone-like hormone (Pthlh) signaling pathways and Dlx5 (distal-less homeobox 5) plays an important role in these processes. The induction of Fgfr2 (Fgf receptor 2) and Fgfr3 expression by Runx2 is important for the proliferation of osteoblast lineage cells. Runx2 induces Sp7 expression, and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Sp7 induces the differentiation of preosteoblasts into osteoblasts without enhancing their proliferation. In osteoblasts, Runx2 is required for bone formation by inducing the expression of major bone matrix protein genes, including Col1a1 (collagen type I alpha 1), Col1a2, Spp1 (secreted phosphoprotein 1), Ibsp (integrin binding sialoprotein), and Bglap (bone gamma carboxyglutamate protein)/Bglap2. Bglap/Bglap2 (osteocalcin) regulates the alignment of apatite crystals parallel to collagen fibrils but does not function as a hormone that regulates glucose metabolism, testosterone synthesis, and muscle mass. Sp7 is also involved in Co1a1 expression and regulates osteoblast/osteocyte process formation, which is necessary for the survival of osteocytes and the prevention of cortical porosity. SP7 mutations cause osteogenesis imperfecta in rare cases. Runx2 is an important pathogenic factor, while Runx1, Runx3, and Cbfb are protective factors in osteoarthritis development.

The Role of a New Hinged Total Knee Arthroplasty System for Use in a Variety of Complex Knee Scenarios: A Case Series.

Hinged knee arthroplasties are commonly used in scenarios where there are major ligament deficiencies or bone loss around the knee. They are applicable in native knees with major deformities and during revisions. They can also be used as a salvage procedure after distal femoral resection. The new modular hinged device system, namely the Triathlon Hinge Knee (THK) System (Stryker, Mahwah, New Jersey), reflects the advancements of third-generation design and enhances surgical flexibility by allowing streamlined integration with the Triathlon Total Stabilized (TS) System (Stryker, Mahwah, New Jersey) and the Global Modular Replacement System (GMRS, Stryker, Mahwah, New Jersey). Additionally, the Triathlon Revision Tibial Baseplate (Stryker, Mahwah, New Jersey) has been launched as part of THK and is compatible with the Modular Rotating Hinge (MRH , Stryker, Mahwah, New Jersey) femur, which allows the Revision Baseplate to replace the existing tibial component while leaving the existing MRH Femoral Component in place. The Triathlon Revision Tibial Baseplate enables orthopaedic surgeons to use constrained or hinged prostheses, including both distal and total femoral replacement options, without changing the Tibial Baseplate. This is because the TS, MRH, THK, and GMRS femurs are compatible with the new Triathlon Revision Tibial Baseplate. Additionally, the system can be augmented with metaphyseal cone constructs to help provide a stable foundation for reconstruction. This report explores the application of a new modular hinged device system in various scenarios, starting with (1) complex primary hinged knee arthroplasty, followed by revision hinged knee arthroplasty cases including (2) failed TKA with medial collateral ligament (MCL) dysfunction, (3) severe arthrofibrosis post-TKA, (4) revisions for prosthetic joint infection, (5) extensor mechanism deficiency, and (6) arthrofibrosis with extensor mechanism disruption, concluding with a case of (7) distal femoral arthroplasty for periprosthetic fracture post-failed TKA.

Health-related quality of life and mental health in patients with major bone and joint infections.

It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome. The SF-36 physical component summary mean at baseline was 30.9 (95% CI 29.7 to 32.0). At one month, it was unchanged (30.5; 95% CI 29.5 to 31.5; p = 0.447); it had improved statistically significantly at six months (35.5; 95% CI 34.2 to 36.7; p < 0.001) and at 12 months (37.9; 95% CI 36.4 to 39.3; p < 0.001). The SF-36 mental component summary mean at baseline was 42.5 (95% CI 40.8 to 44.2). At one month, it was unchanged (43.1; 95% CI 41.4 to 44.8; p = 0.458); it had improved statistically significantly at six months (47.1; 95% CI 45.4 to 48.7; p < 0.001) and at 12 months (46.7; 95% CI 45.0 to 48.5; p < 0.001). All mental subscales had improved by the end of the study, but mental health status remained compromised in comparison with the average USA population. BJIs considerably impact HRQoL, particularly mental health. Patients suffering from BJIs reported considerable limitations in their daily and social activities due to psychological problems. Impaired mental health may be explained by the chronic nature of BJIs, and therefore the mental wellbeing of these patients should be monitored closely.

KNEE DEFORMITIES AND KNEE REPLACEMENTS IN SAUDI POPULATION: OUR EXPERIENCE AND LITERATURE REVIEW

It takes precise alignment, adequate balance, and deformity correction to accomplish a successful total knee arthroplasty (TKA). In main TKA, this can be successfully achieved with a posterior stabilized (PS) design, either with or without sub-periosteal release. However, severe abnormalities with a major bone defect, stiffness, and instability are often associated with these disorders in some circumstances, such as knee osteoarthritis. Additional restrictive prostheses are required since it is extremely difficult to balance these anomalies with soft tissue release alone, even after main TKA. In this situation, the constrained condylar knee (CCK) design is the optimum choice. This studys primary objectives were to characterize the clinical outcomes, function recovery, and complications of patients who underwent primary CCK-TKA for severe knee osteoarthritis related knee deformity. The secondary aim was to find out the mid-term prostheses survival. Methods: Between March 2021 and March 2022, 36 consecutive patients with knee osteoarthritis had cemented primary CCK-TKA. Twenty-Eight women and eight men, totaling 36 patients, had at least a 6 month follow-up for this retrospective analysis. We used the Knee Society Score (KSS), the Hospital for Special Surgery (HSS) score, and the roentgenographic evaluation form to assess the patients. The survival of prosthesis was assessed using Kaplan-Meiers survival analysis. The patients follow-up periods averaged 12 month. The KSS knee score rose from 44 points (23–68) to 91 points (76–100) following surgery [P &lt; 0.001]. Following the procedure, the mean KSS functional score rose from 20–75 points to 91 points (65–100) [P &lt; 0.001]. The average HSS score rose from 51 points (27–83) to 91 points (75–100) following surgery [P &lt; 0.001]. The average range of motion (ROM) also increased after surgery, going from 68.09° ± 35.99° (0°–120°) to 113.68° ± 8.90° (100°–130°) [P &lt; 0.001]. The average hip-knee-ankle (HKA) angle was 180.24° ± 1.77° (175°–184°) following surgery, compared to 176.88° ± 14.48° (135°–199°) before to surgery. Radiolucencies were seen in thirteen knees, mostly on the tibial side. After an average follow-up of 12 month, 94.7% of prosthesis were still in use. Despite severe deformity, instability, and stiffness at a relatively young age, the mid-term follow-up of primary CCK-TKA in knee osteoarthritis gives satisfactory clinical and functional outcomes with 94.7% prosthesis survival. However, there are a few issues.

Fat embolism syndrome after trauma: What you need to know.

Fat embolism syndrome refers to a systemic condition caused by the circulation of fat droplets in the bloodstream, reaching various target organs typically after major bone fractures or related surgical procedures. Although most cases resolve spontaneously, severe instances can lead to significant respiratory failure, neurological damage, and even mortality. Therefore, appropriate prevention, timely diagnosis, and management are crucial for trauma patients at risk. The objective of this review article is to explore the definition, epidemiology, risk factors, clinical presentation, and pathophysiology of fat embolism syndrome. Furthermore, it aims to examine current recommendations for the accurate diagnosis, prevention, and treatment of it, providing a comprehensive guide for the effective management of patients prone to this condition.

Microsurgery in low- and middle-income countries: Results of 20 years of experience in Cambodia

BackgroundMicrosurgical free tissue transfer is the gold standard for reconstructing major bone or soft tissue defects but requires complex training, and specific resources. Therefore, some authors have stated that microsurgery is impossible in low- and middle-income countries. MethodsPatients from Khmer underwent free flap surgery at the Children’s Surgical Centre in Phnom Penh between 2004 and 2023. Two non-governmental organizations facilitated the program: Rose Charities Cambodia provided the facilities, patients and local staff, and Doctors of the World provided the surgeons, and anesthetists. At least one Khmer surgeon was trained during these operations. Digital data were collected retrospectively, and analyzed in June 2023. ResultsFifty-six free flaps in 54 patients have been performed since 2004. The most frequent sites requiring reconstruction were the head and neck (35.7%), lower limbs (30.4%), and upper limbs (21.4%). The most frequent free flaps were free fibula (44.6%), gracilis (19.6%), and anterolateral thigh (16.1%). Among the 56 flaps, 41 (= 73.2%) were viable long-term and 15 (26.7%) were microsurgical failures. Sixteen flaps underwent revision in the operating room. Twenty-three flap-related complications were reported in 21 patients with mostly vascular thrombosis (n = 12), hematoma (n = 3) and infections (3). However, 83.3% had improved or were cured of their initial pathology after final surgical management. ConclusionsFree flaps performed in our series as part of international surgical collaborations in a low-income country are feasible, but we experienced higher failure rates, and later revisions compared to the results in high-income countries. We identified several solutions to improve the microsurgery outcomes in low-income settings.

Complications of revision knee arthroplasty

Due to the growing scale of arthroplasty and the widening of indications for knee joint replacement, the durability of joint functioning has become a critical issue. Untimely diagnosis and inadequate treatment of patients with endoprosthesis component loosening leads to major bone defects. This problem arises from repeated joint interventions, large bone defects and duration of revision surgeries, that is fraught with catastrophic consequences for patients – revision prosthesis removal or even limb amputation. The project aims to improve the treatment for patients with instability of components after knee joint arthroplasty. The aim of the study is to analyze the results of revision knee arthroplasty and identify the causes of mistakes and complications of revision arthroplasty with the intention of prevention. Materials and methods. A retrospective analysis of 50 revision knee arthroplasties performed at the Centre for Arthroplasty of the State Institution “Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine” was conducted. Clinical and radiological findings were evaluated for all patients. All revision prostheses used in this study were of the semi-constrained type. Cementation technique was used for all implants. In the revision of the septic complication group, a full cementation technique with antibiotics according to a sensitivity profile were used, while in the aseptic complication group, a surface cementation technique with antibiotics according to sensitivities were used. Results. The authors of the project have analyzed the results of treatment of 50 revision arthroplasty procedures performed between 2013 and 2022 for instability of the endoprosthesis components. The structure of complications has been examined and the causes of failure in revision knee arthroplasty have been identified. This study has shown promise in preventing complications and developing personalized approaches to revision arthroplasty. Conclusions. The analysis of revision knee arthroplasty failure has shown the prevalence of septic complications (56.0 %). In the case of septic complications after revision arthroplasty, Staphylococcus aureus prevailed (57.1 %), gram (-) microorganisms were causative agents in other cases. Factors resulting in aseptic complications included those associated with the surgical intervention (81.8 %), the patient (45.4 %) and the combination thereof (72.7 %). Significant causes of the femoral revision component loosening were residual valgus deformity, medial instability in the frontal plane; significant causes of the tibial component loosening were residual varus deformity and lateral instability in the frontal plane.

Multi-Quantifying Maxillofacial Traits via a Demographic Parity-Based AI Model.

Objective and Impact Statement: The multi-quantification of the distinct individualized maxillofacial traits, that is, quantifying multiple indices, is vital for diagnosis, decision-making, and prognosis of the maxillofacial surgery. Introduction: While the discrete and demographically disproportionate distributions of the multiple indices restrict the generalization ability of artificial intelligence (AI)-based automatic analysis, this study presents a demographic-parity strategy for AI-based multi-quantification. Methods: In the aesthetic-concerning maxillary alveolar basal bone, which requires quantifying a total of 9 indices from length and width dimensional, this study collected a total of 4,000 cone-beam computed tomography (CBCT) sagittal images, and developed a deep learning model composed of a backbone and multiple regression heads with fully shared parameters to intelligently predict these quantitative metrics. Through auditing of the primary generalization result, the sensitive attribute was identified and the dataset was subdivided to train new submodels. Then, submodels trained from respective subsets were ensembled for final generalization. Results: The primary generalization result showed that the AI model underperformed in quantifying major basal bone indices. The sex factor was proved to be the sensitive attribute. The final model was ensembled by the male and female submodels, which yielded equal performance between genders, low error, high consistency, satisfying correlation coefficient, and highly focused attention. The ensemble model exhibited high similarity to clinicians with minor processing time. Conclusion: This work validates that the demographic parity strategy enables the AI algorithm with greater model generalization ability, even for the highly variable traits, which benefits for the appearance-concerning maxillofacial surgery.

Body shape from birth to adulthood is associated with skeletal development: A Mendelian randomization study

BackgroundObservational studies have shown that childhood obesity is associated with adult bone health but yield inconsistent results. We aimed to explore the potential causal association between body shape and skeletal development. MethodsWe used two-sample Mendelian randomization (MR) to estimate causal relationships between body shape from birth to adulthood and skeletal phenotypes, with exposures including placental weight, birth weight, childhood obesity, BMI, lean mass, fat mass, waist circumference, and hip circumference. Independent genetic instruments associated with the exposures at the genome-wide significance level (P < 5 × 10−8) were selected from corresponding large-scale genome-wide association studies. The inverse-variance weighted analysis was chosen as the primary method, and complementary MR analyses included the weighted median, MR-Egger, weighted mode, and simple mode. ResultsThe MR analysis shows strong evidence that childhood (β = −1.29 × 10−3, P = 8.61 × 10−5) and adulthood BMI (β = −1.28 × 10−3, P = 1.45 × 10−10) were associated with humerus length. Tibiofemoral angle was negatively associated with childhood BMI (β = −3.60 × 10−1, P = 3.00 × 10−5) and adolescent BMI (β = −3.62 × 10−1, P = 2.68 × 10−3). In addition, genetically predicted levels of appendicular lean mass (β = 1.16 × 10−3, P = 1.49 × 10−13), whole body fat mass (β = 1.66 × 10−3, P = 1.35 × 10−9), waist circumference (β = 1.72 × 10−3, P = 6.93 × 10−8) and hip circumference (β =1.28 × 10−3, P = 4.34 × 10−6) were all associated with tibia length. However, we found no causal association between placental weight, birth weight and bone length/width. ConclusionsThis large-scale MR analysis explores changes in growth patterns in the length/width of major bone sites, highlighting the important role of childhood body shape in bone development and providing insights into factors that may drive bone maturation.

Comparative World Literature: Making a Case for Re/Translation

Translation has been a major bone of contention in comparative literature studies. For the longest time it was looked down upon by bona fide comparatists, who insisted on studying literary works in the original. World literature scholars, on the contrary, have from the beginning acknowledged that, given the multiplicity of the world’s languages and their literatures, it was inevitable that one resort to translation to access all but a handful of literatures. The final decades of the 20th century saw the rise of translation studies. Adopting insights and methods from descriptive translation studies might help bridge any putative gap between comparative and world literature studies, also when it comes to transcultural studies.

Bio-Printing of Materials for Bone Tissue Engineering

Abstract: The complicated internal mechanical and structural qualities of normal bone tissue still prevent the development of effective therapeutic procedures for major bone lesions. It is still difficult to use tissue engineering to return damaged bones back to how they were originally intended. Due to recent advances in 3D printing, together with the introduction of new materials and technological assistance, the basis for BTE has been established. Biological 3D biomaterials have cells inside them, which allows for the creation of structures that mimic real tissues. Microextrusion, inkjet, and laser-assisted bioprinting are the three primary methods used in 3D bioprinting manufacturing. Hydrogels packed with cells, growth hormones, and bioactive ceramics are among the bioinks utilized in bone bioprinting. With the use of magnetic resonance imaging or computed tomography scanning, 3D printing offers substantial benefits for tailored treatment by enabling the creation of scaffolds with the right structural qualities, form, and dimensions. Three-dimensional (3D) bioprinting is a cutting-edge technique that has been utilized recently to create multicellular, biomimetic tissues with layers upon layers of intricate tissue microenvironment printing. We approached the use of hydrogels with great strength in 3D printing for BTE with an emphasis on first providing a thorough study about the development of 3D printing, printing techniques, and ink selection in this review. A brief prediction on how 3D printing would advance in the future was made.

Disturbance in the potential cardiovascular-bone-skeletal muscle axis and morbidity and mortality in patients undergoing haemodialysis: the Q-Cohort Study.

Disturbances in the cardiovascular system, bone and skeletal muscle are independent risk factors for death among patients receiving haemodialysis (HD). However, the combined impact of disorders of these three organs on morbidity and mortality is unclear in the HD population. A total of 3031 Japanese patients on maintenance HD were prospectively followed. The outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and bone fracture. Patients were divided into four groups (G1-G4) according to the baseline number of diseased organs represented as histories of cardiovascular disease and bone fractures and the presence of low skeletal muscle mass as follows: G1, no organ; G2, one organ; G3, two organs; G4, three organs. Multivariable-adjusted survival models were used to analyse associations between the number of diseased organs and outcomes. During a 4-year follow-up, 499 deaths, 540 MACE and 140 bone fractures occurred. In the Cox proportional hazards model, the risk for all-cause mortality was significantly higher in G2, G3 and G4 than in G1 as the reference {hazard ratio: G2, 2.16 [95% confidence interval (CI) 1.65-2.84], G3, 3.10 [95% CI 2.27-4.23] and G4, 3.11 [95% CI 1.89-5.14]}. Similarly, the risks for developing MACE and bone fractures were significantly elevated as the number of organ disorders increased. Multiple disorders of the cardiovascular-bone-skeletal muscle axis are strong predictors of morbidity and mortality in patients undergoing HD.

Lower Extremity Open Fractures Fix and Flap: Does Initial Management in Non-specialized Hospitals Really Compromise its Outcome?

Introduction Managing open lower extremity fractures is challenging, with potential complications such as amputation and infection. The aim of the study was to determine whether the time delay and initial treatment of the patients treated in a non-specialized hospital before being transferred to a dedicated level I trauma center led to a worse outcome. Methods Retrospective data from 44 patients (37 males and seven females) undergoing free tissue transfer for lower extremity open fractures from January 2017 to December 2022 were analyzed. Group A received primary care externally and was later transferred for definitive treatment (n=17, 38.6%), while group B received initial care at a level I trauma center (n=27, 61.4%). Surgical outcomes, complications, the duration of the hospital stay, and assessment times were compared. Various demographic variables, co-morbidities, prior interventions, and flap types were analyzed. Results Average age(A: 55.1±16.7;B: 38.7±19.8 years;p=0.041), overall hospitalization (A: 55.7±22.8; B: 42.8±21.3 days;p=0.041), and time to soft tissue reconstruction differed significantly between groups (A: 30.7±12.2; B: 18.9±9.3 days;p=0.013).Overall, 31.8% had multiple injuries without statistical differences between groups A and B (29.4% vs. 33.3%; p>0.05). There were no statistical differences between the groups in terms of major and minor complications and bone healing characteristics. Limb salvage was successful overall in 93.2% (A: 94.1%; B: 92.6%; P>0.05). Major complications occurred in 9.1%; three patients underwent major amputation (A: n=2; B: n=1). Minor complications were observed in 43.2% of patients (partial flap necrosis, wound dehiscence and non-union; A: 41.2%; B: 44.4%; p>0.05). Overall, 65.9% of patients (A: 64.7%; B: 66.7%; p>0.05) experienced uneventful bone healing, while 18.2% of patients (A: 23.5%; B: 14.8%; p>0.05) experienced delayed healing.Flaps used weremostly musculocutaneous(71.7%). Various assessed demographic characteristics, including age and presence of polytrauma, showed no significant influence on complications (p>0.05). Conclusion Although there is a significant difference in the time course of externally treated patients with open fractures, prolonged treatment is not associated with a higher complication rate or compromised bone healing outcome. Despite the findings, it is important to avoid delays and strive for interdisciplinary collaboration.