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P-15 is a 15-amino-acid-long biomimetic peptide widely demonstrated to enhance osteogenesis in vivo. Despite the prevalence of polyether-ether-ketone (PEEK) in interbody device manufacturing, a growing body of evidence suggests it may produce an unfavorable immune response. The purpose of this preliminary study was to characterize the immune response and new bone growth surrounding PEEK implants with and without a P-15 peptide-based osteobiologic. A bilateral femoral defect model was conducted using New Zealand white rabbits. A total of 17 test subjects received one implant in each distal femur, either with or without bone graft material. Animals were allowed to survive to 4 or 8 weeks, at which time the femurs were collected and subjected to micro-computer tomography (microCT) or cytokine analysis. MicroCT analysis included the quantification of bone growth and density surrounding each implant. The cytokine analysis of periprosthetic tissue homogenates included the quantification of interleukins (ILs) and TNF-α expression via ELISA kits. Improvements in bone volume were observed in the P-15 cohort for the regions of interest, 500–136 and 136–0 µm from the implant surface, at 8 weeks post-op. Concentrations of IL-1β, IL-4, and IL-6 cytokines were significantly higher in the P-15 cohort compared to the PEEK cohort at the 4-week timepoint. Significant reductions in the concentrations of IL-4 and IL-6 cytokines from the 4- to 8-week cohort were observed in the P-15 cohort only. The P-15 peptide has the potential to modulate the immune response to implanted materials. We observed improvements in bone growth and a more active micro-environment in the P-15 cohort relative to the PEEK control. This may indicate an earlier transition from the inflammatory to remodeling phase of healing. [ABSTRACT FROM AUTHOR]

Aims: 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. Methods: 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. Results: 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. Conclusion: 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. Cite this article: Bone Jt Open 2024;5(9):721–728.

Traumatic fractures and stress fractures are common orthopedic diseases, and there is great potential in researching bone turnover, repair, and promotion of fracture healing. Basic medical experiments often use animal models of long bone fractures in limbs to study the mechanisms of various interventions on fracture healing. Fracture healing is a complex process influenced by multiple factors and involves multiple molecules and pathways. Therefore, to explore the mechanisms more deeply, accelerate the translation of results, and improve the clinical efficacy, it is particularly important to choose the appropriate animal fracture modeling methods in experimental research. Based on this, this paper conducts a literature review of animal species and modeling methods commonly used for long bone fracture models in experimental research. It summarizes five methods: bone defect method, physical impact method, mechanical bending method, open osteotomy method, and drilling method. A side-by-side comparison of their advantages, disadvantages, and scope of application is made, aiming to provide suitable fracture models for studying the mechanisms of fracture healing interventions.

Because experimental studies to determine the developmental toxicity of exposure to various substances in children are impossible, many studies use immature male rats. This study aimed to provide normative data for longitudinal bone growth with age during the puberty in male rats. In order to evaluate long bone growth and mineralization we examined bone size and bone density by dual-energy X-ray absorptiometry, analyzed histomorphometry of the growth plate, and serum hormone levels relevant to bone growth from postnatal day (PD)20 to PD60. The length and weight of long bones increased strongly by PD40, and no further increase was observed after PD50. On the other hand, tibial growth plate height decreased sharply after PD50 along with a reduction in the number of cells and columns, which was probably responsible for the absence of further lengthening of long bones. Parameters related to bone formation such as bone area ratio, and the thickness and number of trabeculae, also increased significantly between PD40 and PD50. Furthermore, serum levels of IGF-1 peaked at PD30 and testosterone increased rapidly on and after PD40, when IGF-1 levels were going down. These changes may participate in the parallel increase in mineral acquisition, as well as lengthening of long bones. Our findings provide comprehensive data for changes in bone density, histomorphometry of long bones, and hormone levels relevant to bone growth during the growth spurt. This will be useful for planning animal toxicological studies, particularly for deciding on the appropriate age of animals to use in given experiments. [ABSTRACT FROM AUTHOR]

Traumatic fractures and stress fractures are common orthopedic diseases, and there is great potential in researching bone turnover, repair, and promotion of fracture healing. Basic medical experiments often use animal models of long bone fractures in limbs to study the mechanisms of various interventions on fracture healing. Fracture healing is a complex process influenced by multiple factors and involves multiple molecules and pathways. Therefore, to explore the mechanisms more deeply, accelerate the translation of results, and improve the clinical efficacy, it is particularly important to choose the appropriate animal fracture modeling methods in experimental research. Based on this, this paper conducts a literature review of animal species and modeling methods commonly used for long bone fracture models in experimental research. It summarizes five methods: bone defect method, physical impact method, mechanical bending method, open osteotomy method, and drilling method. A side-by-side comparison of their advantages, disadvantages, and scope of application is made, aiming to provide suitable fracture models for studying the mechanisms of fracture healing interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Autologous bone grafting is the standard treatment for the surgical management of atrophic nonunion of long bones. Other solutions, such as bone marrow mesenchymal stem cells (BM-MSC) combined with phospho-calcium material, have also been used. Here we evaluate the safety and early efficacy of a novel procedure using autologous or allogenic adipose tissue mesenchymal stromal cells (AT-MSC) seeded in a patented tricalcium phosphate-based biomaterial for the treatment of bone regeneration in cases of atrophic nonunion. Methods This was a prospective, multicentric, open-label, phase 2 clinical trial of patients with atrophic nonunion of long bones. Biografts of autologous or allogenic AT-MSC combined with a phosphate substrate were manufactured prior to the surgical procedures. The primary efficacy was measured 6 months after surgery, but patients were followed for 12 months after surgery and a further year out of the scope of the study. All adverse events were recorded. This cohort was compared with a historical cohort of 14 cases treated by the same research team with autologous BM-MSC. Results A total of 12 patients with atrophic nonunion of long bones were included. The mean (SD) age was 41.2 (12.1) years and 66.7% were men. Bone healing was achieved in 10 of the 12 cases (83%) treated with the AT-MSC biografts, a percentage of healing similar (11 of the 14 cases, 79%) to that achieved in patients treated with autologous BM-MSC. Overall, two adverse events, in the same patient, were considered related to the procedure. Conclusions The results of this study suggest that AT-MSC biografts are safe for the treatment of bone regeneration in cases of atrophic nonunion and reach high healing rates. Trial registration Study registered with EUDRA-CT (2013-000930-37) and ClinicalTrials.gov (NCT02483364).

Long bone non-unions represent a serious clinical and socioeconomical problem due to the prolonged episodes, frequent sequelae, and variable treatment effectiveness. Bone grafts, classically involving the autologous iliac crest graft as the ‘gold standard’ bone graft, enhance bone regeneration and fracture healing incorporating osteoconductive and/or osteoinductive/osteogenic capacity to the non-union under treatment. Structural alternatives to autologous bone grafts include allografts and bone substitutes, expanding the available stock but loosing biological properties associated with cells in the graft. Biological alternatives to autologous bone grafts include bone marrow concentration from iliac crest aspiration, bone marrow aspiration from reaming of the diaphyseal medullary canal in the long bones, and isolated, expanded mesenchymal stem cells under investigation. When the combination with natural and synthetic bone substitutes allows for larger volumes of structural grafts, the enhancement of the biological regenerative properties through the incorporation of cells and their secretoma permits to foresee new bone grafting solutions and techniques.

Background: Among the risk factors for nonunion are unchangeable patient factors such as the type of injury and comorbidities, and factors that can be influenced by the surgeon such as fracture treatment and the postoperative course. While there are numerous studies analyzing unchangeable factors, there is poor evidence for factors that can be affected by the physician. This raises the need to fill the existing knowledge gaps and lay the foundations for future prevention and in-depth treatment strategies. Therefore, the goal of this study was to illuminate knowledge about nonunion in general and uncover the possible reasons for their development; Methods: This was a retrospective analysis of 327 patients from 2015 to 2020 from a level I trauma center in Germany. Information about patient characteristics, comorbidities, alcohol and nicotine abuse, fracture classification, type of osteosynthesis, etc., was collected. Matched pair analysis was performed, and statistical testing performed specifically for atrophic long-bone nonunion; Results: The type of osteosynthesis significantly affected the development of nonunion, with plate osteosynthesis being a predictor for nonunion. The use of wire cerclage did not affect the development of nonunion, nor did the use of NSAIDs, smoking, alcohol, osteoporosis and BMI; Conclusion: Knowledge about predictors for nonunion and strategies to avoid them can benefit the medical care of patients, possibly preventing the development of nonunion. [ABSTRACT FROM AUTHOR]

Purpose: Primary bone and joint sarcomas of the long bone are relatively rare neoplasms with poor prognosis. An efficient clinical tool that can accurately predict patient prognosis is not available. The current study aimed to use deep learning algorithms to develop a prediction model for the prognosis of patients with long bone sarcoma. Methods: Data of patients with long bone sarcoma in the extremities was collected from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2014. Univariate and multivariate analyses were performed to select possible prediction features. DeepSurv, a deep learning model, was constructed for predicting cancer-specific survival rates. In addition, the classical cox proportional hazards model was established for comparison. The predictive accuracy of our models was assessed using the C-index, Integrated Brier Score, receiver operating characteristic curve, and calibration curve. Results: Age, tumor extension, histological grade, tumor size, surgery, and distant metastasis were associated with cancer-specific survival in patients with long bone sarcoma. According to loss function values, our models converged successfully and effectively learned the survival data of the training cohort. Based on the C-index, area under the curve, calibration curve, and Integrated Brier Score, the deep learning model was more accurate and flexible in predicting survival rates than the cox proportional hazards model. Conclusion: A deep learning model for predicting the survival probability of patients with long bone sarcoma was constructed and validated. It is more accurate and flexible in predicting prognosis than the classical CoxPH model. [ABSTRACT FROM AUTHOR]

Background: The nutrient foramina are cavities contain nutrient arteries and peripheral nerves. The present study was done in Department of Anatomy, L.N. Medical College and Research Centre, Bhopal with 100 dry human femurs. there were 149 foramina in 100 femurs. Mean length of femur 435mm, most frequently seen on Linea aspera of femur foramina index mean was 44.3403 for femur. Right side femur foramina index range 28.52-63.86, left side bone foramina index range 30.65-61.42. Information about number, location, position and direction of nutrient foramina important clinically in orthopedic procedures such as joint replacement therapy, fracture repair and preserving blood supply of graft during vascularized bone grafting. [ABSTRACT FROM AUTHOR]

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Aims: The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. Methods: We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. Results: A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. Conclusion: We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement. Cite this article: Bone Jt Open 2023;4(8):643–651.

Aims: The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. Methods: The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. Results: In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion: This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease. Cite this article: Bone Jt Open 2023;4(6):424–431.

Previous research divided long bone growth into intramembranous and endochondral ossification. The latter contributes to longitudinal bone growth through the addition of new bone tissue at the physeal growth plate. Bones, also, increase in thickness through appositional bone growth of the cortical bone. The aim of the present study was to investigate the age-related histomorphometrical changes that occur during the growth of the humerus in rats as a model of the long bone. Samples were collected for light microscopy from the right humerus at 3, 4, 6, 8, 10, 13, and 20 weeks (wks) of age. Histological investigation revealed that the distal physeal growth plate could be detected at 3 wks of age, while at 4 wks of age it was replaced by bone trabeculae. Morphometrically, differences were observed in the thickness of the proximal physeal growth plate, specifically its proliferative zone. The thickness of the proliferative zone initially decreased, then showed a significant increase around the age of puberty (6–8 wks), then decreased significantly from 8–20 wks of age. The midshaft cortical bone thickness showed a significant increase during the study. In conclusion, ageing affected both longitudinal and appositional growth, which both participated in the growth and development of the rat's humerus.

This article analyzed the imaging features of 18 long bone metastasis (LBM) of renal cell carcinoma (RCC) confirmed by pathology and reviewed the available literature. Patients who underwent radiographic examinations at our hospital between January 2015 and December 2021 with pathology-confirmed bone metastases were evaluated. The clinical and radiographs and CT, and MR images features of the patients were analyzed. Eighteen patients with pathology-confirmed LBM from RCC were collected. All the patients had X-ray examinations, 15 had computed tomography (CT), 13 had magnetic resonance (MR) imaging, and six had MR enhancement. The clinical and imaging features of the lesions were analyzed, including morphological and signal intensity characteristics. Ten patients were found with metastases after nephrectomy, and eight patients were admitted to the hospital with skeletal-related events (SREs). Eighteen cases originated from clear cell RCC. Fourteen lesions were located in the epiphysis and four in the diaphysis. The height-to-width ratio of the lesions ranged from 1.11 to 3.41 (mean, 1.84). All lesions showed osteolytic destruction, with 16 lesions showing expansile destruction. Seven lesions demonstrated soap bubble hyperintensity and hypointense separation on T2-weighted images. Six lesions demonstrated a flow-void sign, and six showed marked marginal enhancement. The LBM of RCC mainly occurred in the proximal epiphysis and tended to spread along the long bone axis with expansile osteolytic destruction. In some cases, soap bubble hyperintensity, hypointense separation, and the flow-void sign were seen. [ABSTRACT FROM AUTHOR]

Abstract Background There is a paucity of data regarding the prevalence of preoperative deep vein thrombosis (DVT) in patients with long bone (including femur, tibia and fibula) fractures of the lower limbs. We performed a meta-analysis to address the issue. Methods Electronic databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, the VIP database, CNKI, and the Wanfang database, were systematic searched for original articles that reported the prevalence of preoperative DVT in long bone fractures of the lower limbs from January 2016 to September 2021. The prevalence of preoperative DVT was pooled using random-effects models, and subgroups were established according to study type, detection method, sample size and fracture site. Results Twenty-three articles reporting on 18,119 patients were eligible. The overall pooled preoperative DVT prevalence was 24.1% (95% CI 19.3–28.8%). In different subgroups, the preoperative DVT prevalences were 18.2–27.3%, 15.2–28.6%, 23.1–24.9%, 18.2–26.0% and 23.2–23.4% for different study designs, sample sizes, age groups, detection methods and fracture sites, respectively. Conclusions Despite the heterogeneity among studies, this systematic review suggests that the prevalence of preoperative DVT, which may seriously affect the prognosis of patients, is high. Therefore, greater efforts should be devoted to the improvement of screening and prevention strategies for preoperative DVT in lower-extremity long bone fractures. Level of Evidence: Level III. Trial Registration The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42022324706.

To compare the efficacy of recombinant human bone morphogenetic proteins (rhBMPs) and autologous bone graft (ABG) on the healing of long bone non-union. A systematic literature search was conducted on PubMed, Web of Science, Cochrane Library, and CNKI up to December 2021. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. A Meta-analysis was performed using state software (version 12.0). A total of 14 studies were included in this meta-analysis. Overall, there was no significant difference between the rhBMPs group and the ABG group in terms of healing rate (RR = 1.04, 95% CI = 0.96–1.12, p = 0.365) and healing time (SMD = −0.31, 95% CI = −0.76–0.14, p = 0.175). Subgroup analysis showed rhBMPs lead to higher healing rates (RR = 1.35, 95% CI = 1.17–1.56, p < 0.001), and shorter healing time (SMD = −0.65, 95% CI = −1.08 to −0.22, p = 0.003) in the subgroup of moderate-quality studies. Sensitivity analysis proved that our conclusions were relatively robust. No significant publication bias was recognized in all studies (Begg's test, p = 0.193; Egger's test, p = 0.307). RhBMPs or combined with allografts bone, inorganic bone was a valid alternative to ABG for the treatment of long bone non-union. • The largest scale meta-analysis for rhBMPs in long bone non-union. • RhBMPs can replace autologous bone graft (ABG) in these cases; • The combination of rhBMPs and ABG was not desirable in these cases; • The outcomes were associated with the quality of the included studies. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data regarding the prevalence of preoperative deep vein thrombosis (DVT) in patients with long bone (including femur, tibia and fibula) fractures of the lower limbs. We performed a meta-analysis to address the issue. Methods: Electronic databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, the VIP database, CNKI, and the Wanfang database, were systematic searched for original articles that reported the prevalence of preoperative DVT in long bone fractures of the lower limbs from January 2016 to September 2021. The prevalence of preoperative DVT was pooled using random-effects models, and subgroups were established according to study type, detection method, sample size and fracture site. Results: Twenty-three articles reporting on 18,119 patients were eligible. The overall pooled preoperative DVT prevalence was 24.1% (95% CI 19.3–28.8%). In different subgroups, the preoperative DVT prevalences were 18.2–27.3%, 15.2–28.6%, 23.1–24.9%, 18.2–26.0% and 23.2–23.4% for different study designs, sample sizes, age groups, detection methods and fracture sites, respectively. Conclusions: Despite the heterogeneity among studies, this systematic review suggests that the prevalence of preoperative DVT, which may seriously affect the prognosis of patients, is high. Therefore, greater efforts should be devoted to the improvement of screening and prevention strategies for preoperative DVT in lower-extremity long bone fractures. Level of Evidence: Level III. Trial Registration The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42022324706. [ABSTRACT FROM AUTHOR]

Introduction: Globally, injuries account for about 5 million deaths every year out of which 90% occur in low- and middle-income countries. Injuries, particularly trauma, place a lifelong burden on affected individuals, families and society. In Ghana and most African countries particularly in sub-Saharan Africa, there is no effective surveillance system or registry of trauma. Where they exist, they are often poorly developed and incomplete. Objective: The study was set out to document long bone fracture injuries which will be used for research, education, policy and public health prevention programmes as well as documenting the experience in setting up trauma registries in a LMIC. Methods: The study is being conducted at the four Teaching Hospitals in Ghana which are situated in Cape Coast, Kumasi, Accra and Tamale. Persons of any age (from birth) who reports to any of the sentinel sites with an incident of trauma to long bones are eligible for recruitment into the surveillance data collection. Data were captured using the Research Electronic Data Capture (REDCap), cleaned and exported to Stata for analysis. Results: Cumulatively, the sites had enrolled 3493 cases at one year of implementation. A total of 678 (19.41%) paediatric and 2815 (80.59%) adult cases were recorded over the period. In the establishment of the TRANET, we identified challenges in the planning, during data collection, data entry, follow-ups, support from local health authorities, and administrative issues. Quality improvement interventions were put in place, and it resulted in improved data quality. Conclusion: The established trauma registry of Ghana is assuring as it offers a timely, accurate, and comprehensive data source which will be useful for continuous monitoring of trauma care in Ghana. This first-year review information/findings will serve as a relevant information for stakeholders working to strengthen the health system. [ABSTRACT FROM AUTHOR]

Aims: There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. Methods: A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. Results: Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. Conclusion: The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465–476.

Abstract Background The recombinant human bone morphogenetic protein (rhBMP) is a common graft substitute for treating cases of long bone nonunion. However, the feasibility of combining an autologous bone graft (ABG) with rhBMPs remains uncertain. Thus, this systematic review and meta-analysis aimed to evaluate the synergistic effect of ABG and rhBMPs on the healing of long bone nonunion. Methods A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. Statistical analyses were performed using Stata 12.0. Results Of the 202 citations, five studies involving a total of 394 cases met the eligibility criteria; thus, they were included in this study. The pooled data revealed no significant differences among the groups in terms of postoperative healing rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.96–1.06, P = 0.744), healing time (standardised mean difference = − 0.20, 95% CI = − 0.95–0.56, P = 0.610), and pain (RR = 1.44, 95% CI = 0.25–8.29, P = 0.681). The combination of ABG and rhBMPs resulted in good limb function (RR = 1.31, 95% CI = 1.04–1.66, P = 0.023). Conclusions The combination of ABG and rhBMPs did not result in the healing of long bone nonunion and pain reduction. Nevertheless, it conferred good limb function. Thus, the findings in this study are insufficient to support the use of rhBMPs as an adjuvant to ABG.

Background: The nutrient foramina are cavities that conduct the nutrient arteries and the peripheral nerves on the shaft of long bones. Long bones receive most of the blood supply from the nutrient arteries. The knowledge about position and number of the nutrient foramen is helpful for medico legal cases, anthropological study and orthopaedic surgeons during different surgical procedures. Aims and Objectives: To determine the topography, direction and number of the nutrient foramina in upper and lower limb long bones in Telangana, India. Materials and Method: This observational cross section study was conducted in the department of anatomy; Medical colleges of Telangana states. The number, direction and site of the foramina were noted in all the long bones. A total of 326 long bones of upper and lower limb were examined. Results: Out of total 326 long bones 165 were from upper limb and 161 were from lower limb. The single solitary nutrient foramina were noted in most of the bones. The site of the foramina was mainly on middle third of shaft (except tibia, foramina mainly in upper third of shaft). Maximum number of foramina was found on femur (94) followed by Humerus (74). Conclusion: The present study provides information on the number, position, and direction of nutrient foramina of the long bones. This may help in surgical procedures and in the interpretation of radiological images. [ABSTRACT FROM AUTHOR]

Abstract Background The autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb. Method This study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up. Results Fourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18–56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication. Conclusion Cortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use.

Introduction Literature data and analysis of our own material indicate a change in the density of the long bone cortical plate in patients with chronic osteomyelitis along its extension; however, the nature and degree of structural disorders of the cortical layer beyond the inflammation zone is an unexplored area of radiomorphology. Objective To study the structural features of the cortical plate of the femur and tibia outside the inflammation nidus and the change in its structure in the form of trabecularization. Material and methods The study is retrospective single-center work of level of evidence IV. In 86 patients with chronic osteomyelitis of the long bones of the lower extremities, using polypositional radiography and multislice computed tomography (MSCT), the features of radiological morphology of the femur and tibia were studied in order to identify structural features and quantify the density of the cortical plate and its trabecularization. Results The cause of the inflammatory process in the bone in 83 cases was trauma or surgery, and consequences of hematogenous osteomyelitis in three cases. The most common location of chronic osteomyelitis was the distal femur (24) and tibia (25) bones. Due to long-term disease, nonunion or a bone defect developed in 11 patients. Analysis of MSCT data in 86 patients with chronic osteomyelitis showed that anatomical changes in the femur and tibia and the density characteristics of the cortical plate near the focus of destruction were manifested in 79.5 % of patients with a decrease in the thickness of the cortical plate (up to 2 mm) with complete trabecularization in separate areas with density from 290 to 360HU in 47.7 % of the examined. Conclusion Radiological morphological changes in the cortical plate of the femur and tibia in patients with chronic osteomyelitis near the focus of destruction were characterized by a decrease in the thickness and density of the cortical plate, accompanied by its complete or partial trabecularization with a density not exceeding 315.5 ± 38.6 Hounsfield units (HU) in 41 ( 47.7 %) of 86 patients.

Introduction It is known that the density of the cortical plate of long bones in patients with chronic osteomyelitis changes throughout its extension. However, the nature of structural disorders in the cortical layer outside the inflammation zone has not been studied well. Purpose To study the structural features of the cortical plate of the femur and tibia outside the focus of inflammation to identify microcavities and microabscesses. Material and methods The study is retrospective conducted at one center. Evidence level IV. In 92 patients with chronic osteomyelitis of long bones of the lower extremities, using polypositional radiography and multislice computed tomography (MSCT), the features of radiological morphology of the femur and tibia were studied in order to reveal structural features of the cortical plate and identify microcavities. Results The cause of osteomyelitis in 5 cases was a consequence of hematogenous osteomyelitis, and in 87 cases it developed due to trauma or surgery. The most common location of chronic osteomyelitis was the distal femur and tibia. Anatomical changes in the femur and tibia in all patients had individual differences. Radiological morphological manifestations such as local and general osteoporosis, foci of osteosclerosis, architectonic disorders occurred in all patients. However, the severity of changes in the bone structure was extremely diverse, including the changes in bone density. Conclusion The data obtained indicate that radiological morphological changes in the cortical plate outside the zone of destruction are manifested by formation of microcavities and microabscesses in 15.6 % of patients, what plays an important role in possible recurrence of osteomyelitis.

Purpose: The impact on bone union of injecting bone marrow from the anterior iliac crest was examined in patients with non-unions. Materials and Methods: The present study was prepared following a retrospective study on non-union patients who applied to our clinics who accepted bone marrow injection and were followed up and monitored after the procedure. A total of 14 bones from 13 patients with long bone diaphysis and metaphysis non-union were included in the study from among patients who applied during the dates of November 2016 – December 2019. Bone marrow aspiration from the anterior iliac crest was conducted on the patients under anesthesia which was injected to the fracture line under local anesthesia and fluoroscopy. All patients were monitored on a monthly basis with front-rear and side radiography. The injection operation was conducted three times on seven patients and 2 times on a total of seven non-unions in 6 patients. Results: A total of 11 unions took place in 14 patients. A union could not be attained in three fractures. The gap was over 2 mm in fractures without union. Fracture union ratio was obtained as 79 %. The mean injection number applied on the patients was 2.5. A statistically significant correlation could not be identified between the fixation method and non-union type and union. Conclusion: Bone marrow injection is a cheap, effective, easy to use and safe surgical method for the treatment of long bone fractures with non-union.

PURPOSE: The aim of this study was to investigate the prevalence of long bone fractures among cats, presented at the Small Animal Clinic, Faculty of Veterinary Medicine, Trakia University, a center that attracts cases from all over Bulgaria, and to analyze their seasonal, breed-, sex- and age-related distribution. METHODS: The study cohort comprised 267 cats with long bone fractures. All patients were analyzed retrospectively for a period of five years (2016 to 2020). Data about cat signalment (breed, sex, age, body weight) and fractured bone were evaluated. RESULTS: The cases with fractured femur were statistically significantly (p=0.0001) more prevalent (n=139; 52.06%) than those of all other affected long bones. Long bone fracture tended to occur most commonly in male (54.68%), than female (45.32%) cats. Statistically significantly (p

Background: Reconstruction of stature from broken fragments of bones is used as a part of the analysis in forensic anthropology for the purpose of identification of an individual. Long bones are traditionally used for estimation of stature. Long bones such as femur and tibia are the most important components of an individual’s stature. In the present study, regression equation was derived for estimation of maximum femoral length from measurements of the proximal end of femur. Aims and Objectives: To derive regression equations using femur length from measurements of neck-shaft angle and maximum vertical diameter of femur head. Materials and Methods: Two hundred unpaired femurs, devoid of gross pathology and irrespective of gender obtained from the Department of Anatomy of both VMKVMC &VMHMC were used for this study. The correlation coefficients of the neck-shaft angle and maximum diameter of head of femur to the maximum length of femur was calculated. These co-efficient were used for formulation of regression equation. Results: The present study was done to show that the maximum length of femur can be best calculated from the metric evaluation of vertical diameter of the head when the proximal fragments are available. The parameters in our study which includes maximum vertical diameter of the head showed positive correlation but the neck- shaft angle showed a low correlation and is not reliable to measure MFL from it. Conclusion: The present study concludes that the maximum length of femur can be best calculated from the metric evaluation of vertical diameter of the head when the proximal fragments are available.

Abstract Background The management of an infected nonunion of long bones is difficult and challenging. A staged procedure comprising radical debridement followed by definitive internal fixation was favored. However, no standard treatment has been established to determine the appropriate waiting period between initial debridement and definitive internal fixation. We propose a management method that incorporates early definitive internal fixation in infected nonunion of the lower limb. Methods Thirty-four patients (28 men and 6 women; mean age 46.09 years; range 25–74 years) with infected nonunion of the tibia or femur were included. Initial infected bone resection and radical debridement were performed in each patient in accordance with the preoperative plans. Definitive surgery was performed 2–3 weeks after the resection (4 weeks after flap surgery was required), and a third surgery was performed to fill the bone defect through bone grafting or transport (three-stage surgery). In cases of unplanned additional surgery, the reason for the requirement was analyzed, and radiological and functional results were investigated in accordance with the Association for the Study and Application of the Method of Ilizarov criteria. Results Bone union was achieved in all patients, and treatment was conducted as planned preoperatively in 28 patients (28/34, 82.35%). The mean interval between primary debridement and secondary definitive fixation was 2.76 weeks (range 2–4 weeks). Six unplanned additional surgeries were performed, and the infection relapsed in two cases. The radiological and functional outcomes were good or better in 32 and 31 patients, respectively. Conclusions Early definitive surgery can be performed to treat infected nonunion by thorough planning and implementation of radical resection, active response to infection, restoration of defective bones, and soft tissue healing through a systemic approach.

Treating open fractures in long bones can be challenging and if not performed properly can lead to poor outcomes such as mal/non-union, deformity, and amputation. One of the most common methods of treating these fracture types is temporary external fixation followed by definitive fixation. The shortage of high-quality affordable external fixators is a long-recognised need, particularly in Low- and Middle-Income Countries (LMICs). This research aimed to develop a low-cost device that can be manufactured locally to international standards. This can provide surge capacity for conflict zones or in response to unpredictable incidents and situations. The fixator presented here and developed by us, the Imperial external fixator, was tested on femur and tibia specimens under 100 cycles of 100 N compression-tension and the results were compared with those of the Stryker Hoffmann 3 frame. The Imperial device was stiffer than the Stryker Hoffmann 3 with a lower median interfragmentary motion (of 0.94 vs. 1.48 mm). The low-cost, easy to use, relatively lightweight, and easy to manufacture (since minimum skillset and basic workshop equipment and materials are needed) device can address a critical shortage and need in LMICs particularly in conflict-affected regions with unpredictable demand and supply. The device is currently being piloted in three countries for road traffic accidents, gunshot wounds and other conflict trauma—including blast cohorts.

Bone mechanical properties are classically determined by biomechanical tests, which normally destroy the bones and disable further histological or molecular analyses. Thus, obtaining biomechanical data from bone usually requires an additional group of animals within the experimental setup. Finite element models (FEMs) may non-invasively and non-destructively simulate mechanical characteristics based on material properties. The present study aimed to establish and validate an FEM to predict the mechanical properties of mice tibiae. The FEM was established based on µCT (micro-Computed Tomography) data of 16 mouse tibiae. For validating the FEM, simulated parameters were compared to biomechanical data obtained from 3-point bending tests of the identical bones. The simulated and the measured parameters correlated well for bending stiffness (R2 = 0.9104, p < 0.0001) and yield displacement (R2 = 0.9003, p < 0.0001). The FEM has the advantage that it preserves the bones' integrity, which can then be used for other analytical methods. By eliminating the need for an additional group of animals for biomechanical tests, the established FEM can contribute to reducing the number of research animals in studies focusing on bone biomechanics. This is especially true when in vivo µCT data can be utilized where multiple bone scans can be performed with the same animal at different time points. Thus, by partially replacing biomechanical experiments, FEM simulations may reduce the overall number of animals required for an experimental setup investigating bone biomechanics, which supports the 3R (replace, reduce, and refine) principle. [ABSTRACT FROM AUTHOR]

The Late Cretaceous (Maastrichtian) Ruth Mason Dinosaur Quarry (RMDQ) represents a monodominant Edmontosaurus annectens bonebed from the Hell Creek Formation of South Dakota and has been determined as a catastrophic death assemblage likely belonging to a single population, providing an ideal sample to investigate hadrosaurid growth and population dynamics. For this study, size‐frequency distributions were constructed from linear measurements of long bones (humeri, femora, tibiae) from RMDQ that revealed five relatively distinct size classes along a generally right‐skewed distribution, which is consistent with a catastrophic assemblage. To test the relationship between morphological size ranges and ontogenetic age classes, subsets from each size‐frequency peak were transversely thin‐sectioned at mid‐diaphysis to conduct an ontogenetic age assessment based on growth marks and observations of the bone microstructure. When combining these independent datasets, growth marks aligned with size‐frequency peaks, with the exclusion of the overlapping subadult‐adult size range, indicating a strong size‐age relationship in early ontogeny. A growth curve analysis of tibiae indicated that E. annectens exhibited a similar growth trajectory to the Campanian hadrosaurid Maiasaura, although attaining a much larger asymptotic body size by about 9 years of age, further suggesting that the clade as a whole may have inherited a similar growth strategy. This rich new dataset for E. annectens provides new perspectives on other hypotheses of hadrosaurid life history. When the RMDQ population was compared with size distributions from other hadrosaurid bonebed assemblages, juveniles (categorized as ages one and two) were either completely absent from or heavily underrepresented in the samples, providing support for the hypothesized segregation between juvenile and adult hadrosaurids. Osteohistological comparison with material from polar and temperate populations of Edmontosaurus revealed that previous conclusions correlating osteohistological growth patterns with the strength of environmental stressors were a result of sampling non‐overlapping ontogenetic growth stages. [ABSTRACT FROM AUTHOR]

Background: The autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb. Method: This study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up. Results: Fourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18–56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication. Conclusion: Cortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use. [ABSTRACT FROM AUTHOR]

Sex estimation from human skeletal remains is of vital importance in the buildup of a biological profile of an individual in medico-legal and bioarchaeological studies. The present study is focused on the estimation of sex from osteometric measurements of the complete femur and its fragmentary parts, and the development of a web based application related to this. Fifteen osteometric measurements were taken from 78 dry cadaveric femurs from the Faculty of Medicine, University of Kelaniya. Using R software, linear discriminant analysis and logistic regression methods were applied to build classification models with the help of the application of a stepwise procedure, to identify the best combination of measurements to estimate the sex of the femur. A cross-validation method was applied to estimate the predictive accuracy of each model. Since the linear discriminant analysis model gave more predictive accuracy than the regression model, we suggest using linear discriminant analysis to estimate the sex using osteometric measurements of the femur. From the whole femur measurements, a formula to determine sex was developed with highest total accuracy of 83 % using four parameters; epicondylar breadth, anteroposterior mid-shaft diameter, bi-trochanter length, and maximum shaft diameter. Similarly, measurements of transverse head diameter and bi-trochanter length with a total accuracy of 76 % for the proximal part of the femur, measurements of anteroposterior mid-shaft diameter with a total accuracy of 77 % for the mid-shaft, and measurements of epicondylar breadth and maximum length of the lateral condyle with a total accuracy of 70 % for the distal part of the femur were identified as significant discriminants to determine sex, and formulae were written accordingly. Average accuracy ranged from 83 % to 70 %, with male accuracy slightly higher than that of females. A web application to estimate the sex of femur using these formulae was developed and this will be of great importance for forensic medicine and bio-archaeological research in Sri Lanka. [ABSTRACT FROM AUTHOR]

Background: The recombinant human bone morphogenetic protein (rhBMP) is a common graft substitute for treating cases of long bone nonunion. However, the feasibility of combining an autologous bone graft (ABG) with rhBMPs remains uncertain. Thus, this systematic review and meta-analysis aimed to evaluate the synergistic effect of ABG and rhBMPs on the healing of long bone nonunion. Methods: A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. Statistical analyses were performed using Stata 12.0. Results: Of the 202 citations, five studies involving a total of 394 cases met the eligibility criteria; thus, they were included in this study. The pooled data revealed no significant differences among the groups in terms of postoperative healing rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.96–1.06, P = 0.744), healing time (standardised mean difference = − 0.20, 95% CI = − 0.95–0.56, P = 0.610), and pain (RR = 1.44, 95% CI = 0.25–8.29, P = 0.681). The combination of ABG and rhBMPs resulted in good limb function (RR = 1.31, 95% CI = 1.04–1.66, P = 0.023). Conclusions: The combination of ABG and rhBMPs did not result in the healing of long bone nonunion and pain reduction. Nevertheless, it conferred good limb function. Thus, the findings in this study are insufficient to support the use of rhBMPs as an adjuvant to ABG. [ABSTRACT FROM AUTHOR]

Abstract Background Overall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures. Methods In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated. Results During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed. Conclusion This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment. Trial registration NCT02020590 . Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures.

Objectives: Biological mortality bias is the idea that individuals who comprise skeletal samples (non‐survivors) are a specific subset of the overall population, who may have been exposed to greater stress during life. Because of this, it is possible that studying growth in a skeletal population misrepresents the growth and health of survivors in that population. Using a modern sample, this study investigates whether biological mortality bias in growth may be present in archaeological skeletal samples. Materials and methods: Postmortem computed tomography scans of 206 children aged under 13 years were collected from two institutions in the United States and Australia. The sample was separated into children who died from natural causes as proxies for non‐survivors and from accidental causes as proxies for survivors. Differences in long bone length for age were assessed through analysis of covariance (ANCOVA) and z‐score analysis, and these results were compared with studies linking anthropometrics and mortality risk in nonindustrialized societies. Results: Differences in growth favoring survivors were greater for girls than for boys and seemed to increase over age. The effect in nonindustrialized societies was 1.5 to 5 times the magnitude of that in our contemporary sample. Conclusions: A greater growth delay in girls than in boys has been documented in historical identified collections, and skeletal samples consistently become more stunted relative to modern standards over the course of growth. Our findings on biological mortality bias could explain part of these growth delays and impact interpretations of past ontogenetic environments. [ABSTRACT FROM AUTHOR]

Background: Nonunion is one of the most challenging problems in the field of orthopedics. The aim of this study was to perform a systematic review of the literature to evaluate the effectiveness of extracorporeal shockwave therapy (ESWT) in the treatment of nonunion in long bones. Methods: We conducted a search of three databases (PubMed, Scopus, and Web of Science) and found 646 total publications, of which 23 met our inclusion criteria. Results: Out of 1200 total long bone nonunions, 876 (73%) healed after being treated with ESWT. Hypertrophic cases achieved 3-fold higher healing rates when compared to oligotrophic or atrophic cases (p = 0.003). Metatarsal bones were the most receptive to ESWT, achieving a healing rate of 90%, followed by tibiae (75.54%), femurs (66.9%) and humeri (63.9%). Short periods between injury and treatment lead to higher healing rates (p < 0.02). Conversely, 6 months of follow-up after the treatment appears to be too brief to evaluate the full healing potential of the treatment; several studies showed that healing rates continued to increase at follow-ups beyond 6 months after the last ESWT treatment (p < 0.01). Conclusions: ESWT is a promising approach for treating nonunions. At present, a wide range of treatment protocols are used, and more research is needed to determine which protocols are the most effective. [ABSTRACT FROM AUTHOR]

The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway plays important roles in the development and growth of the skeleton. Apert syndrome caused by gain‐of‐function mutations of FGFR2 results in aberrant phenotypes of the skull, midface, and limbs. Although short limbs are representative features in patients with Apert syndrome, the causative mechanism for this limb defect has not been elucidated. Here we quantitatively confirmed decreases in the bone length, bone mineral density, and bone thickness in the Apert syndrome model of gene knock‐in Fgfr2S252W/+ (EIIA‐Fgfr2S252W/+) mice. Interestingly, despite these bone defects, histological analysis showed that the endochondral ossification process in the mutant mice was similar to that in wild‐type mice. Tartrate‐resistant acid phosphatase staining revealed that trabecular bone loss in mutant mice was associated with excessive osteoclast activity despite accelerated osteogenic differentiation. We investigated the osteoblast–osteoclast interaction and found that the increase in osteoclast activity was due to an increase in the Rankl level of osteoblasts in mutant mice and not enhanced osteoclastogenesis driven by the activation of FGFR2 signaling in bone marrow‐derived macrophages. Consistently, Col1a1‐Fgfr2S252W/+ mice, which had osteoblast‐specific expression of Fgfr2 S252W, showed significant bone loss with a reduction of the bone length and excessive activity of osteoclasts was observed in the mutant mice. Taken together, the present study demonstrates that the imbalance in osteoblast and osteoclast coupling by abnormally increased Rankl expression in Fgfr2S252W/+ mutant osteoblasts is a major causative mechanism for bone loss and short long bones in Fgfr2S252W/+ mice. [ABSTRACT FROM AUTHOR]

Ultrasound imaging plays a critical role in diagnostics in biomedicine because of its safety, nature, and low cost. Conventional ultrasound systems form images using a focused beam during transmission and dynamic focusing during the reception. The area under examination can be simultaneously insonified using a plane wave, which allows for ultrafast data capture rates but lowers image quality. The resultant image can be improved by coherent plane-wave compounding, in which numerous plane waves are released at different angles to produce distinct image datasets that are then blended to improve the final composite image. This study used the Fourier-domain technique for coherent plane-wave compounding image reconstruction from the image produced by conventional ultrasound to investigate the quality of the image produced compared to the X-ray image. To establish the merits and limitations of this approach, the researchers provided quantitative comparisons with the images obtained by the X-ray machine. The evaluation results are based on the peak signal-to-noise ratio (PSNR), mean, and variance. The results obtained showed that the migration method can precisely image the cortical bone fracture and offer good contrast between the bone tissue and the subcutaneous tissues. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. Methods Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. Results Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. Conclusions The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.

Background: Osteosarcoma (OS), most commonly occurring in long bone, is a group of malignant tumors with high incidence in adolescents. No individualized model has been developed to predict the prognosis of primary long bone osteosarcoma (PLBOS) and the current AJCC TNM staging system lacks accuracy in prognosis prediction. We aimed to develop a nomogram based on the clinicopathological factors affecting the prognosis of PLBOS patients to help clinicians predict the cancer-specific survival (CSS) of PLBOS patients. Method: We studied 1199 PLBOS patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and randomly divided the dataset into training and validation cohorts at a proportion of 7:3. Independent prognostic factors determined by stepwise multivariate Cox analysis were included in the nomogram and risk-stratification system. C-index, calibration curve, and decision curve analysis (DCA) were used to verify the performance of the nomogram. Results: Age, Histological type, Surgery of primary site, Tumor size, Local extension, Regional lymph node (LN) invasion, and Distant metastasis were identified as independent prognostic factors. C-indexes, calibration curves and DCAs of the nomogram indicating that the nomogram had good discrimination and validity. The risk-stratification system based on the nomogram showed significant differences (P

PURPOSE: The aim of this study was to investigate the prevalence of long bone fractures among cats, presented at the Small Animal Clinic, Faculty of Veterinary Medicine, Trakia University, a center that attracts cases from all over Bulgaria, and to analyze their seasonal, breed-, sex- and age-related distribution. METHODS: The study cohort comprised 267 cats with long bone fractures. All patients were analyzed retrospectively for a period of five years (2016 to 2020). Data about cat signalment (breed, sex, age, body weight) and fractured bone were evaluated. RESULTS: The cases with fractured femur were statistically significantly (p=0.0001) more prevalent (n=139; 52.06%) than those of all other affected long bones. Long bone fracture tended to occur most commonly in male (54.68%), than female (45.32%) cats. Statistically significantly (p<0.0001) younger cats (65.54%) were presented with long bone fractures than adult animals (34.46%). In 71.54% of the cases the body weight was 2 - 4 kg, in 14.61% - 4 - 6 kg, in 12.36% under 2 kg and in 1.49 % over 6 kg. CONCLUSION: In general, young male cats with body weight more than 2 kg were mainly affected. Most commonly encountered fractures were those of the femur, followed in descending order by fractures of the tibia, radius/ulna and humerus. [ABSTRACT FROM AUTHOR]

Purpose: The impact on bone union of injecting bone marrow from the anterior iliac crest was examined in patients with non-unions. Materials and Methods: The present study was prepared following a retrospective study on non-union patients who applied to our clinics who accepted bone marrow injection and were followed up and monitored after the procedure. A total of 14 bones from 13 patients with long bone diaphysis and metaphysis non-union were included in the study from among patients who applied during the dates of November 2016 – December 2019. Bone marrow aspiration from the anterior iliac crest was conducted on the patients under anesthesia which was injected to the fracture line under local anesthesia and fluoroscopy. All patients were monitored on a monthly basis with frontrear and side radiography. The injection operation was conducted three times on seven patients and 2 times on a total of seven non-unions in 6 patients. Results: A total of 11 unions took place in 14 patients. A union could not be attained in three fractures. The gap was over 2 mm in fractures without union. Fracture union ratio was obtained as 79 %. The mean injection number applied on the patients was 2.5. A statistically significant correlation could not be identified between the fixation method and non-union type and union. Conclusion: Bone marrow injection is a cheap, effective, easy to use and safe surgical method for the treatment of long bone fractures with non-union. [ABSTRACT FROM AUTHOR]

Abstract Background Bone morphogenetic proteins (BMPs) have strong bone induction properties and can promote healing of fractures and other defects. However, BMP treatment efficacy for long bone nonunion remains controversial. The aim of this meta-analysis was to synthetically evaluate the advantages and disadvantages of BMP plus bone grafting (observation group) versus autologous bone grafting (control group) for limb long bone nonunion. Methods PubMed, Embase, Web of Science, Cochrane Library, OVID, CNKI, Weipu Journal, Chinese Biomedical Literature, and WanFang were searched for randomized and non-randomized controlled trials published before November 2019. A meta-analysis of outcome indicators was performed using RevMan 5.3 and Stata 12.0. Results Five randomized and four non-randomized controlled trials involving 30–124 cases were included, with a total of 655 nonunion cases. There were no significant group differences in postoperative healing rate, infection, and secondary operation rates (P > 0.05), but the study group demonstrated significantly shorter mean healing time (WMD = − 1.27, 95%CI − 1.67 to − 0.88, P < 0.00001), a greater frequency of excellent/good post-treatment limb function (RR = 1.18, 95%CI 1.01–1.39, P = 0.04), and lower intraoperative blood loss (P < 0.05). Alternatively, the hospitalization cost was significantly higher in the study group (P < 0.01). Conclusions Bone morphogenetic protein is a viable alternative to autologous bone grafting, with potential advantages of accelerated fracture healing and improved postoperative function.

Introduction Long bone refractures can be a common injury among pediatric population. Approaches to rehabilitation of children with refractures are similar to those used for primary injuries. However, refracture healing and bone repair involve specific pathways that should be considered in rehabilitative approaches to restorative treatment. Objective To identify morphological specific features of simulated reparative processes in long bone refractures of growing animals (rats) at different stages of observation. Material and methods Two series of experiments were carried out on 36 laboratory animals (rats) to explore histological picture at the healing site of primary and repeat fractures at different stages of reparative process. Transverse fracture of the tibial shaft was simulated and fixed with external fixation device in the first series (n = 18). Tibial shaft was refractured and fixed again with external fixation device after 21 days of primary injury in the second series (n = 18). Results Delayed osteogenesis and greater period of organotypical regenerate restructuring were observed in animals with long bone refractures. Mechanism of slower osteogenesis was found to be associated with disturbed blood supply affecting cell differentiation at the refracture site. Conclusion Delayed bone repair and longer period of organotypical regenerate restructuring were specifically detected in growing animals with long bone refractures.

Background: The management of an infected nonunion of long bones is difficult and challenging. A staged procedure comprising radical debridement followed by definitive internal fixation was favored. However, no standard treatment has been established to determine the appropriate waiting period between initial debridement and definitive internal fixation. We propose a management method that incorporates early definitive internal fixation in infected nonunion of the lower limb. Methods: Thirty-four patients (28 men and 6 women; mean age 46.09 years; range 25–74 years) with infected nonunion of the tibia or femur were included. Initial infected bone resection and radical debridement were performed in each patient in accordance with the preoperative plans. Definitive surgery was performed 2–3 weeks after the resection (4 weeks after flap surgery was required), and a third surgery was performed to fill the bone defect through bone grafting or transport (three-stage surgery). In cases of unplanned additional surgery, the reason for the requirement was analyzed, and radiological and functional results were investigated in accordance with the Association for the Study and Application of the Method of Ilizarov criteria. Results: Bone union was achieved in all patients, and treatment was conducted as planned preoperatively in 28 patients (28/34, 82.35%). The mean interval between primary debridement and secondary definitive fixation was 2.76 weeks (range 2–4 weeks). Six unplanned additional surgeries were performed, and the infection relapsed in two cases. The radiological and functional outcomes were good or better in 32 and 31 patients, respectively. Conclusions: Early definitive surgery can be performed to treat infected nonunion by thorough planning and implementation of radical resection, active response to infection, restoration of defective bones, and soft tissue healing through a systemic approach. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma is a rare, but aggressive malignant neoplasm of monocyte/macrophage lineage with a wide age distribution. Bone involvement is exceedingly rarer compared to the lymph node, skin, and soft tissue, and no long bone involvement has been reported in the English literature. We here report 2 cases of histiocytic sarcoma involving the long bone: one from the femur of a 77-year-old female, status post the placement of an intramedullary nail for subtrochanteric hip fracture; the other from the radius of a 3-year-old female with no significant medical history. Radiologic imaging showed highly destructive lesions in both cases with soft-tissue extension. Microscopy in both cases showed sheets of polygonal mononuclear cells with abundant eosinophilic cytoplasm, prominent nucleoli, and frequent mitosis. Hemophagocytosis were also identified. Immunohistochemistry showed that the lesional cells were strongly diffusely positive for CD68 and CD163. The first patient deteriorated rapidly, despite the aggressive treatment of amputation and chemotherapy. However, the second patient is disease free 36 months post the treatment of amputation only. We conclude that the long bone could be the primary site of histiocytic sarcoma. Its prognosis could be very variable and it is difficult to predict its behavior based on morphological evaluation only. [ABSTRACT FROM AUTHOR]