Femoral Marrow Research Articles

Comparison of Early Postoperative Stress Distribution around Short and Tapered Wedge Stems in Femurs with Different Femoral Marrow Cavity Geometries Using Finite Element Analysis.

In total hip arthroplasty (THA), the ideal stem length remains uncertain; different stem lengths are used in different cases or institutions. We aimed to compare the stress distributions of cementless tapered wedges and short stems in femurs with different femoral marrow geometries and determine the appropriate fit. Finite element models were created and analyzed using HyperMesh and LS-DYNA R11.1, respectively. The 3-dimensional shape data of the femurs were extracted from computed tomography images using the RETOMO software. Femurs were divided into 3 groups based on the Dorr classification. The computer-aided design data of cementless tapered wedge-type and short stems were used to select the appropriate size. In the finite element analysis, the loading condition of the femur was assumed to be walking. Volumes of interest (VOIs) were placed within the femur model at the internal and external contact points of the stem based on Gruen zones. The average stresses and strain energy density (SED) of the elements included in each VOI were obtained from the preoperative and postoperative models. The von Mises stress and SED distributions of the cementless tapered wedge and short stems were similar in their respective Dorr classifications. In both stems, the von Mises stress and SED after THA were lower than before THA. The von Mises stress and SED of the cementless tapered wedge stem were higher than those of short stems. Cementless tapered wedge-type stems tended to have lower rates of change than short stems; however, Dorr C exhibited the opposite trend. In the Dorr classification comparison, the von Mises stress and SED were greater for both stems in the order of Dorr C > Dorr B > Dorr A, from Zone 2 to Zone 6. In Dorr A and B, the short stem exhibited a natural stress distribution closer to the preoperative femur than the tapered wedge stem; however, in Dorr C, the short stem may have a greater effect on stress distribution, suggesting that it may cause greater effects, such as fracture in the early postoperative period, than other Dorr types.

Monte Carlo-based in-depth morphological analysis of medullary cavity for designing personalized femoral stem.

The design of femoral stem prostheses requires a precise understanding of the femoral marrow cavity. Traditional measurements of morphological parameters in the upper femur, particularly the medullary cavity and cortical region, are primarily based on coronal and sagittal axes, which may not fully capture the true three-dimensional structure of the femur. Propose a Monte Carlo-based method for a more comprehensive analysis of the femoral marrow cavity, using CT scans of femurs from a selected group of patients. The study aimed to define and calculate anatomically semantic morphological parameters to enhance the understanding of the femoral marrow cavity's anatomical morphological changes, ultimately improving the design and clinical selection of femoral stem prostheses. To enhance the accuracy of femoral stem prosthesis design, this study aims to develop a Monte Carlo-based method for a more comprehensive analysis of the femoral marrow cavity. The proposed method transforms the non-random problem of determining cross-sectional size into a random issue, allowing for the calculation of the size of the medullary cavity and cortical region. Anatomically semantic morphological parameters are then defined, calculated, and analyzed. The experimental results indicate that the newly defined parameters complement existing ones, providing a more rational scientific basis for understanding the anatomical morphological changes of the femoral marrow cavity. This research offers essential scientific theoretical support for improved morphologic research, design, and clinical selection of femoral stem prostheses. It holds significant importance and application value in clinical practice, contributing to a more accurate and comprehensive understanding of femoral anatomy for prosthetic design.

ДИФФЕРЕНЦИАЛЬНАЯ ЭКСПРЕССИЯ ГЕНОВ МОЛЕКУЛ АДГЕЗИИ И МЕЖКЛЕТОЧНОГО ВЗАИМОДЕЙСТВИЯ В МИКРОЭКСПЛАНТАХ КОСТНОГО МОЗГА ПРИ МОДЕЛИРОВАНИИ МИКРОГРАВИТАЦИИ

Functional activity of the bone marrow cells is dependent on external signals received from a local microenvironment. In addition to the soluble growth factors and hormones, contacts with neighbor cells and signals from the extracellular matrix are also the most important homeostasis regulators in the bone marrow niche. Purpose of the work is to explore the effects of simulated microgravity on the transcription activity of genes the products of which define the cell-to-cell and cell-to-matrix interactions in bone marrow micro-explants. Femoral marrow cells from male mice BalbC 19-20 wks of age were used in the investigation. After isolation, bone marrow cells were pooled and exposed to simulated microgravity in vitro over 14 days. Following the exposure, bone marrow micro-explants were found to increase expression of genes of the cell adhesion molecules responsible for cell-to-cell interaction (Ncam1, Icam1, Vcam1), and integrins α-М (Itgam) and β-1 (Itgb1). Also, there was a reliable decrease in expression of genes involved in the cell-to-matrix interaction, including integrins β-3 (Itgb3), β-2 (Itgb2), α-Х (Itgax), α-l (Itga1), α-5 (Itga5), receptor CD44 (Cd44), and molecules of the adhesion complexes, such as α- and β-katenins (Ctnna1, Ctnnb1). These changes in the pattern of cells-to-environment interaction may induce disorders in self-renewal, proliferation and differentiation of stromal and hemopoietic precursors which may end up with distortion of hemopoiesis, change in bone homeostasis leading to osteopenia observed after space missions.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

Deciphering the Differential Impact of Thrombopoietin/MPL Signaling on Hematopoietic Stem Cell Function in Bone Marrow and Spleen

Introduction Thrombopoietin (TPO) and its receptor MPL are key regulators of hematopoietic stem cell (HSC) function. In humans, ablation of either TPO or MPL leads to bone marrow failure in the early years of life. In contrast, mice lacking TPO or MPL display marked thrombocytopenia and severely reduced HSC numbers but manage to maintain normal survival up to one year of age. In this study, we investigated whether these mice eventually develop marrow failure with longer follow up, with a specific focus on understanding the effects of TPO/MPL signaling on HSC regulation in different hematopoietic niches. Methods Marrow and spleen hematopoiesis in the TPO -/- mice and MPL -/- mice were examined during a 2-yr follow-up. Results At 2 yrs of age, TPO -/- and MPL -/- mice exhibited not only a severely decreased platelet count (TPO -/- vs. MPL -/- vs. control: 38 vs. 107 vs. 1255 x 10 9/L) but also a moderate reduction in neutrophil count compared to age-matched wild-type controls (TPO -/- vs. MPL -/- vs. control: 1.1 vs. 1.7vs.3.3 x 10 3/ul). Femur marrow cell count or spleen cell count was not significantly different between TPO -/- or MPL -/- mice and control mice. There was no significant difference in overall survival between the TPO -/- or MPL -/- mice and wild-type controls. Marrow Lin -cKit +Sca1 +CD150 +CD48 - HSC cell numbers were significantly decreased in young (4-6mo) TPO -/- and MPL -/- mice (~4-fold) compared to age-matched control mice. This HSC loss was further worsened in old (~24mo) TPO -/- (25-fold) and MPL -/- (12-fold) mice compared to control mice. In contrast, there was no significant difference in splenic HSC cell numbers between young TPO -/- or MPL -/- mice and control mice, with only a moderate decrease of HSCs in old TPO -/- and MPL -/- (~4-fold) mice compared to control mice. I n vivo using BrdU labeling revealed an increased proliferation of marrow HSCs in TPO -/- and MPL -/- mice compared to age-matched control mice. In contrast, there was no significant increase in splenic HSC proliferation in TPO -/- or MPL -/- mice. These findings suggest that TPO/MPL signaling has distinct effects on both the number and the function of HSCs in the marrow and spleen. Competitive repopulation assays revealed that HSCs from 2yr old TPO -/- or MPL -/- marrow failed to engraft the recipient mice at 12 weeks post-transplantation. We also conducted competitive repopulation assays in which spleen cells from old TPO -/- mice (CD45.2) were injected together with spleen cells from 2yr old wild-type competitor mice (CD45.1) into lethally irradiated wild-type recipients (CD45.1). At 12 days after transplantation, the TPO -/- spleen donor showed comparable engraftment in the Lin -cKit +Sca1 + stem/progenitor cell compartment, similar to the wild-type competitor spleen donor, suggesting that at least the short-term engraftment capacity of the TPO -/- spleen donor was not impaired. We are currently conducting further investigation to assess the long-term repopulation capacity of TPO -/- spleen HSCs. To investigate how TPO/MPL ablation impacts the hematopoietic niche in the marrow and spleen, we used quantitative flow cytometry and/or fluorescence imaging to examine these niche cells and their expression of niche factors. First, while there was no significant difference in the marrow vascular area (measured by in vivo VE-cadherin labeling) between TPO -/- or MPL -/- mice and control mice, we observed a significant increase in the splenic vascular area in TPO -/- and MPL -/- mice. Second, CXCL12 levels were significantly decreased in marrow endothelial cells (ECs; CD45 -CD31 +) from TPO -/- and MPL -/- mice compared to control mice; in contrast, CXCL12 levels were significantly increased in splenic ECs from TPO -/- and MPL -/- mice. Similar results were also observed with marrow and splenic perivascular stromal cells (CD45 -CD31 -Ter119 -Sca1 -). Therefore, TPO/MPL ablation enhanced both the quantity and quality of the splenic hematopoietic niche, which could contribute to the maintenance of splenic hematopoiesis in TPO -/- and MPL -/- mice. Last, consistent with findings from the TPO/MPL ablated mice, exogenous TPO treatment increased marrow HSC proliferation but did not alter splenic HSC proliferation. In addition, TPO treatment increased CXCL12 expression in marrow ECs, but decreased CXCL12 levels in splenic ECs. Taken together, our study revealed the complexity of TPO/MPL signaling in HSC regulation which differs between the marrow and spleen

Vertebrae but not femur marrow fat transiently decreases in response to body weight loss in an 18-month randomized control trial.

Increased levels of bone marrow adipose tissue (BMAT) are negatively associated with skeletal health and hematopoiesis. BMAT is known to increase with age; however, the effect of long-term weight loss on BMAT is still unknown. In this study, we examined BMAT response to lifestyle-induced weight loss in 138 participants (mean age 48 y; mean body mass index 31kg/m2), who participated in the CENTRAL-MRI trial. Participants were randomized for dietary intervention of low-fat or low-carb, with or without physical activity. Magnetic resonance imaging (MRI) was used to quantify BMAT and other fat depots at baseline, six and eighteen months of intervention. Blood biomarkers were also measured at the same time points. At baseline, the L3 vertebrae BMAT is positively associated with age, HDL cholesterol, HbA1c and adiponectin; but not with other fat depots or other metabolic markers tested. Following six months of dietary intervention, the L3 BMAT declined by an average of 3.1%, followed by a return to baseline after eighteen months (p<0.001 and p=0.189 compared to baseline, respectively). The decrease of BMAT during the first six months was associated with a decrease in waist circumference, cholesterol, proximal-femur BMAT, and superficial subcutaneous adipose tissue (SAT), as well as with younger age. Nevertheless, BMAT changes did not correlate with changes in other fat depots. We conclude that physiological weight loss can transiently reduce BMAT in adults, and this effect is more prominent in younger adults. Our findings suggest that BMAT storage and dynamics are largely independent of other fat depots or cardio-metabolic risk markers, highlighting its unique functions.

Isolation and Molecular Characterisation of Respirovirus 3 in Wild Boar.

Paramyxoviruses are important pathogens affecting various animals, including humans. In this study, we identified a paramyxovirus in 2004 (180608_2004), isolated from a sample of the femoral marrow bone of a wild boar carcass imported from Australia. Antigenic and morphological characteristics indicated that this virus was similar to members of the family Paramyxoviridae. The complete genome phylogenetic analysis grouped this virus into genotype A of bovine parainfluenza virus type 3 (BPIV-3), recently renamed bovine respirovirus type 3 (BRV3), which also includes two swine paramyxoviruses (SPMV)-Texas-81 and ISU-92-isolated from encephalitic pigs in the United States in 1982 and 1992, respectively. The wild boar 180608_2004 strain was more closely related to both the BRV3 shipping fever (SF) strain and the SPMV Texas-81 strain at the nucleotide and amino acid levels than the SPMV ISU-92 strain. The high sequence identity to BRV3 suggested that this virus can be transferred from cattle to wild boars. The potential for cross-species transmission in the Respirovirus genus makes it essential for intensified genomic surveillance.

Daytime administration of melatonin has better protective effects on bone loss in ovariectomized rats

ObjectiveTo explore the difference in the protective effects of intraperitoneal injection of exogenous melatonin of daytime or nighttime on bone loss in ovariectomized (OVX) rats.MethodsAfter bilateral ovariectomy and sham surgery, 40 rats were randomly divided into four groups: sham operation group (Sham), ovariectomy (OVX), and daytime melatonin injection group (OVX + DMLT, 9:00, 30 mg/kg/d) and nighttime injection of melatonin (OVX + NMLT, 22:00, 30 mg/kg/d). After 12 weeks of treatment, the rats were sacrificed. The distal femur, blood and femoral marrow cavity contents were saved. The rest of the samples were tested by Micro-CT, histology, biomechanics and molecular biology. Blood was used for bone metabolism marker measurements. CCK-8, ROS, and Cell apoptosis are performed using MC3E3-T1 cells.ResultsCompared with treatment at night, the bone mass of the OVX rats was significantly increased after the daytime administration. All microscopic parameters of trabecular bone increased, only Tb.Sp decreased. Histologically, the bone microarchitecture of the OVX + DMLT was also more dense than the bone microarchitecture of the OVX + LMLT. In the biomechanical experiment, the femur samples of the day treatment group were able to withstand greater loads and deformation. In molecular biology experiments, bone formation-related molecules increased, while bone resorption-related molecules decreased. After treatment with melatonin administration at night, the expression of MT-1β was significantly decreased. In cell experiments, the MC3E3-T1 cells treated with low-dose MLT had higher cell viability and greater efficiency in inhibiting ROS production than the MC3E3-T1 cells treated with high-dose MLT, which in turn more effectively inhibited apoptosis.ConclusionDaytime administration of melatonin acquires better protective effects on bone loss than night in OVX rats.

Electrical Sympathetic Neuromodulation Protects Bone Marrow Niche and Drives Hematopoietic Regeneration during Chemotherapy.

The sympathetic nervous system (SNS) of the bone marrow regulates the regeneration and mobilization of hematopoietic stem cells. Chemotherapy can damage bone marrow SNS, which impairs hematopoietic regeneration and aggravates hematologic toxicities. This leads to long-term bone marrow niche damage and increases mortality in patients undergoing chemotherapy. Electrical neuromodulation has been used to improve functional recovery after peripheral nerve injury. This study demonstrates that electrical sympathetic neuromodulation (ESN) of bone marrow can protect the bone marrow niche from chemotherapy-induced injury. Using carboplatin-treated rats, the SNS via the sciatic nerve innervating the femoral marrow with the effective protocol for bone marrow sympathetic activation is electrically stimulated. ESN can mediate several hematopoietic stem cells maintenance factors and promote hematopoietic regeneration after chemotherapy. It also activates adrenergic signals and reduces the release of pro-inflammatory cytokines, particularly interleukin-1 β, which contribute to chemotherapy-related nerve injury. Consequently, the severity of chemotherapy-related leukopenia, thrombocytopenia, and mortality can be reduced by ESN. As a result, in contrast to current drug-based treatment, such as granulocyte colony-stimulating factor, ESN can be a disruptive adjuvant treatment by protecting and modulating bone marrow function to reduce hematologic toxicity during chemotherapy.

Intramembranous bone regeneration in diversity outbred mice is heritable.

There are over one million cases of failed bone repair in the U.S. annually, resulting in substantial patient morbidity and societal costs. Multiple candidate genes affecting bone traits such as bone mineral density have been identified in human subjects and animal models using genome-wide association studies (GWAS). This approach for understanding the genetic factors affecting bone repair is impractical in human subjects but could be performed in a model organism if there is sufficient variability and heritability in the bone regeneration response. Diversity Outbred (DO) mice, which have significant genetic diversity and have been used to examine multiple intact bone traits, would be an excellent possibility. Thus, we sought to evaluate the phenotypic distribution of bone regeneration, sex effects and heritability of intramembranous bone regeneration on day 7 following femoral marrow ablation in 47 12-week old DO mice (23 males, 24 females). Compared to a previous study using 4 inbred mouse strains, we found similar levels of variability in the amount of regenerated bone (coefficient of variation of 86% v. 88%) with approximately the same degree of heritability (0.42 v. 0.49). There was a trend toward more bone regeneration in males than females. The amount of regenerated bone was either weakly or not correlated with bone mass at intact sites, suggesting that the genetic factors responsible for bone regeneration and intact bone phenotypes are at least partially independent. In conclusion, we demonstrate that DO mice exhibit variation and heritability of intramembranous bone regeneration that will be suitable for future GWAS.

Osseointegration and Remodeling of Mineralized Bone Graft Are Negatively Impacted by Prior Treatment with Bisphosphonates.

Bisphosphonates limit resorption by inhibiting osteoclast formation and activation. They are removed during preparation of demineralized bone matrix (DBM) particles, but it is not known if osteogenesis and incorporation of mineralized bone allografts from patients treated with oral bisphosphonates are affected in vivo. Human block allografts from 3 bisphosphonate-treated donors and 3 age and sex-matched control donors who had not received bisphosphonates were obtained (Musculoskeletal Transplant Foundation); one-half from each donor was demineralized. In the first study, 3 × 2-mm mineralized and demineralized cylindrical grafts were implanted bilaterally in the femoral metaphysis of 56 rats. In the second study, samples from each group were pooled, prepared as particles, and implanted bilaterally in the femoral marrow canal of 24 rats. Osseointegration, defined as native bone in contact with allograft, was assessed at 10 weeks by micro-computed tomography (CT) and histomorphometry. Micro-CT showed greater bone volume in sites treated with demineralized samples compared with the control mineralized and bisphosphonate-exposed mineralized samples. More new bone was generated along the cortical-endosteal interface compared with mineralized samples. Histology showed significantly less new bone in contact with the mineralized bisphosphonate-exposed allograft (10.4%) compared with mineralized samples that did not receive bisphosphonates (22.8%) and demineralized samples (31.7% and 42.8%). A gap was observed between native bone and allograft in the bisphosphonate-exposed mineralized samples (0.50 mm 2 ). The gap area was significantly greater compared with mineralized samples that did not receive bisphosphonates (0.16 mm 2 ) and demineralized samples (0.10 and 0.03 mm 2 ). Mineralized allografts were osseointegrated, but not remodeled or replaced by living bone, preventing full regeneration of the bone defect. Prior treatment of the donor with bisphosphonates affected osteogenesis, preventing osteointegration and remodeling of the allograft into the regenerating bone. Clinical use of mineralized allografts from patients who had received bisphosphonate therapy needs to be evaluated; in this animal model, such grafts were not integrated into the host bone or remodeled, and full regeneration of the bone defects was prevented.

MicroRNA-148a-3p is a candidate mediator of increased bone marrow adiposity and bone loss following spinal cord injury.

Spinal cord injury is often followed by osteoporosis characterized by rapid and severe bone loss. This leads to an increased risk of osteoporotic fracture in people with spinal cord injury, resulting in increased healthcare costs, morbidity, and mortality. Though it is common, the mechanisms underlying this osteoporosis are not completely understood and treatment options are limited. No biomarkers have been identified for predicting fracture risk. In this study, we sought to investigate microRNA mediated mechanisms relating to osteoporosis following spinal cord injury. We studied subjects with acute SCI (n=12), chronic SCI (n=18), and controls with no SCI (n=23). Plasma samples from all subjects underwent transcriptomic analysis to quantify microRNA expression, after which miR-148a-3p was selected for further study. We performed CT scans of the knee on all subjects with SCI and analyzed these scans to quantify bone marrow adipose tissue volume. MiR-148a-3p was upregulated in subjects with acute SCI vs chronic SCI, as well as in acute SCI vs no SCI. Subjects with chronic SCI had greater levels of marrow adiposity in the distal femoral diaphysis compared to subjects with acute SCI. MiR-148a-3p levels were negatively associated with distal femoral diaphysis marrow adiposity. A multivariable model showed that miR-148a-3p and BMI explained 24% of variation in marrow adiposity. A literature search revealed that miR-148a-3p has multiple bone and fat metabolism related targets. Our findings suggest that miR-148a-3p is a mediator of osteoporosis following spinal cord injury and a potential future therapeutic target.

Bone Marrow Relative Biological Effectiveness for a 212Pb-labeled Anti-HER2/neu Antibody

We have determined the in vivo relative biological effectiveness (RBE) of an alpha-particle-emitting radiopharmaceutical therapeutic agent (212Pb-labeled anti-HER2/neu antibody) for the bone marrow, a potentially dose-limiting normal tissue. The RBE was measured in mice using femur marrow cellularity as the biological endpoint. External beam radiation therapy (EBRT), delivered by a small-animal radiation research platform was used as the reference radiation. Alpha-particle emissions were delivered by 212Bi after the decay of its parent nuclide 212Pb, which was conjugated onto an anti-HER2/neu antibody. The alpha-particle absorbed dose to the marrow after an intravenous administration (tail vein) of 122.1 to 921.3 kBq 212Pb-TCMC-7.16.4 was calculated. The mice were sacrificed at 0 to 7 days after treatment and the radioactivity from the femur bone marrow was measured. Changes in marrow cellularity were assessed by histopathology. The dose response for EBRT and 212Pb-anti-HER2/neu antibody were linear-quadratic and linear, respectively. On transforming the EBRT dose-response relationship into a linear relationship using the equivalent dose in 2-Gy fractions of external beam radiation formalism, we obtained an RBE (denoted RBE2) of 6.4, which is independent of cellularity and absorbed dose. Because hematologic toxicity is dose limiting in almost all antibody-based RPT, in vivo measurements of RBE are important in helping identify an initial administered activity in phase 1 escalation trials. Applying the RBE2 and assuming typical antibody clearance kinetics (biological half-life of 48 hours), using a modified blood-based dosimetry method, an average administered activity of approximately 185.5 MBq (5.0 mCi) per patient could be administered before hematologic toxicity is anticipated.

Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study

SummaryWe assessed lower-limb geometry in adults with X-linked hypophosphatemia (XLH) and controls. We found large differences in multiple measures including femoral and tibial torsion, bowing and cross-sectional area and acetabular version and coverage which may contribute to clinical problems such as osteoarthritis, fractures and altered gait common in XLH.PurposeIndividuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These two factors may be linked, as altered biomechanics is a risk factor for osteoarthritis. This exploratory evaluation aims at providing clues and concepts for this association to facilitate future larger-scale and longitudinal studies on that aspect.MethodsFor this observational study, 13 patients with XLH, aged 18–65 years (6 female), were compared with sex-, age- and weight-matched healthy individuals at a single German research centre. Femoral and hip joint geometry, including femoral and tibial torsion and femoral and tibial shaft bowing, bone cross-sectional area (CSA) and acetabular version and coverage were measured from magnetic resonance imaging (MRI) scans.ResultsTotal femoral torsion was 29° lower in individuals with XLH than in controls (p < 0.001), mainly resulting from lower intertrochanteric torsion (ITT) (p < 0.001). Femoral lateral and frontal bowing, tibial frontal bowing, mechanical axis, femoral mechanical–anatomical angle, acetabular version and acetabular coverage were all greater and tibial torsion lower in individuals with XLH as compared to controls (all p < 0.05). Greater femoral total and marrow cavity CSA, greater tibial marrow cavity CSA and lower cortical CSA were observed in XLH (all p < 0.05).DiscussionWe observed large differences in clinically relevant measures of tibia and particularly femur bone geometry in individuals with XLH compared to controls. These differences may plausibly contribute to clinical manifestations of XLH such as early-onset osteoarthritis, pseudofractures and altered gait and therefore should be considered when planning corrective surgeries.

Exosomes derived from NGF-overexpressing bone marrow mesenchymal stem cell sheet promote spinal cord injury repair in a mouse model

Cell transplantation has been an appealing way to improve the recovery of motor, sensory, and autonomic functions following spinal cord injury (SCI). Herein, we sought to elucidate the function of bone marrow mesenchymal stem cells (BMSCs) sheet in the progression of SCI and its underlying mechanism. BMSCs were extracted from bone marrow of femur and tibia collected from C57BL/6 mice, and the BMSC sheet was prepared when cells grew to 100% confluence after approximately 14 days. Exosomes (Exos) derived from BMSCs were isolated and characterized. The expression of NGF in the isolated Exos and neural stem cells (NSCs) was quantified. NSCs were co-cultured with Exos derived from the BMSC sheet that was treated with overexpressed NGF (oe-NGF) (Exos-oe-NGF). NSC differentiation, axonal regeneration and locomotor function were detected in vitro and in vivo. The BMSC sheet was successfully prepared and exerted a promoting effect on NSC differentiation into neuronal cells and axonal regeneration after SCI by releasing Exos. Co-culture data showed that NGF was highly expressed in the BMSC sheet-loaded Exos and facilitated neuronal differentiation of NSCs and axonal regeneration. In vivo experimental results unveiled that transplantation of BMSC sheet-loaded Exos-oe-NGF into SCI mice displayed enhanced functional recovery. Collectively, Exo-oe-NGF loaded on the BMSC sheet can accelerate NSC differentiation, axonal regeneration and SCI repair, therefore offering us with a potential therapeutic target for treating SCI.

DISEASE BURDEN OF AVASCULAR NECROSIS OF FEMORAL HEAD IN NON-TRAUMATIC HIP PAIN WITH REVIEW OF LITERATURE

Objective: Avascular Necrosis happens to be one of the most common diseases in patients presenting with a chronic painful hip. We have evaluated these patients in the background of demographic details. Material and Method: Prospective study evaluating 319 patients using conventional X-ray and MRI. Imaging findings were evaluated and staging of AVN was done on both modalities. Demographic details were documented in the background of clinical settings. Results: 10.6% of the cases were diagnosed on X-Ray (34 patients). Sequential MRI examination picked up 21% MRI (68 patients). X-ray was missing the diagnosis of AVN in nearly 50% of the cases. 46% of the cases (147 patients) were from age groups ranging from 20-40 years, followed by older patients. It is comparatively rare in young, and if present is associated with other systemic diseases. 60% of the patients were male and 40% of the patients were females. Bilateral hip pain was present in 31% of the cases (100 patients). Right side involvement (37%) was slightly more common than left (32%) in cases with unilateral hip pain. Commonly encountered imaging findings associated were femoral head marrow oedema in 59 patients (87%), double-line sign in 54 patients (79%), subchondral cysts in 42 patients (62%), followed by joint effusion, joint space reduction, femoral head altered contour, femoral head fragmentation with collapse. Conclusion: X-ray alone can miss up to 50% of the cases of Avascular Necrosis of the femoral head, especially in milder and potentially salvageable cases. Correct imaging interpretation and grading make the role of MRI pivotal.

Vertebrae But Not Femur Marrow Fat Transiently Decreases in Response to Body Weight Loss in an 18-Month Randomized Control Trial

Vertebrae But Not Femur Marrow Fat Transiently Decreases in Response to Body Weight Loss in an 18-Month Randomized Control Trial

Fatty Acid Composition of Proximal Femur Bone Marrow Adipose Tissue in Subjects With Systemic Lupus Erythematous Using 3T Magnetic Resonance Spectroscopy.

Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease with common musculoskeletal manifestations, notably reductions in bone quality. Bone marrow adipose tissue composition and quantity has been previously linked to bone quality and may play a role in SLE pathophysiology but has not been thoroughly studied. To use magnetic resonance spectroscopy (MRS) to investigate bone marrow adipose tissue quantity and composition in proximal femur subregions of untreated SLE patients compared to controls and treated patients. Prospective. A total of 64 female subjects: 28 SLE, 15 glucocorticoid (GC)-treated SLE and 21 matched controls. Stimulated echo acquisition mode (STEAM) sequence at 3 T. MRS was performed at multiple echo times in the femoral neck and trochanter regions and fatty acids (FA) composition was computed. Intergroup comparisons were carried out using ANOVA. A P value < 0.05 was considered statistically significant. SLE patients had significantly higher saturated FA compared to controls in both the femoral neck (+0.12) and trochanter (+0.11), significantly lower monounsaturated FA in the trochanter compared to controls (-0.05), and significantly lower polyunsaturated FA in the femoral neck compared to both controls (-0.07) and SLE patients on GC therapy (-0.05). SLE patients have altered proximal femur marrow fat metabolism, which may reflect a manifestation of, or play a role in, the altered inflammatory response of these patients. 2 TECHNICAL EFFICACY: Stage 2.

In vivo typing of Escherichia coli obtained from laying chickens with the E. coli peritonitis syndrome

ABSTRACT Fourteen genetically different chicken Escherichia coli strains were biotyped in hens to examine if any E. coli strain at high dose can induce the E. coli peritonitis syndrome (EPS). Moreover, biotyping was performed in embryos and the median lethal dose (LD50) of three strains was determined in hens. Nine strains were obtained from femur marrow and one strain from caecum of hens that had died from EPS. One strain originated from the inflamed pericardium of a broiler and three strains from the cloaca of specified pathogen-free (SPF) broiler breeders. Strains were inoculated intratracheally into separate groups of 32 productive SPF White Leghorn (WL) hens at a dose of 7.8–9.2 log10 colony forming units (CFU) per hen and into the allantoic cavity of separate groups of 20 SPF WL embryos incubated during 14 days in a dose of 4.2–4.6 log10 CFU per embryo. The embryo test was replicated. Bone marrow and pericardium strains induced EPS, the other strains did not. Based on mortality in hens, EPS-inducing strains could be classified as very virulent (59–100% mortality), moderately virulent (38% mortality) and low virulent (6% mortality). In productive SPF WL hens, the LD50 of three very virulent strains ranged from <2.7 to 5.3 log10 CFU. Virulent and avirulent strains killed 60–95% and 0–30% of embryos, respectively. The embryo lethality test, which showed good reproducibility, did not discriminate within virulent strains, but can nevertheless be considered as a useful alternative for biotyping E. coli in productive hens. RESEARCH HIGHLIGHTS Even at high doses, no E. coli strain could induce EPS. Substantial differences in virulence exist within very virulent E. coli strains. The embryo lethality test is a useful alternative for biotyping E. coli in laying hens. Broiler colibacillosis may represent a source of EPS strains for layers and vice versa.

Optical and thermal fields induced in the bone marrow by external laser irradiation

In regenerative medicine, the problem of growing mesenchymal stem cells from the bone marrow often arises. In such cases is important that the number of initial cells was large enough and their proliferative activity was high. We believe that this problem can be solved by short-term heating of local areas of the bone marrow in vivo with laser radiation. In this regard, it is of interest to study the optical and temperature fields induced inside the tubular bone under external laser irradiation. In this work, we obtained experimental data on the spatial distribution of temperature in the bone marrow of the rat femur in vitro under external exposure to laser radiation with wavelengths of 970 and 1940nm. Radiation delivery was carried out using an optical fiber which tip contacted the surface of the femur bone. A thin thermocouple was used to measure the temperature in a local area of the bone marrow. By moving the optical fiber tip discretely along the longitudinal axis of the bone, and the thermocouple in the perpendicular direction, the spatial temperature distributions in dynamics were measured. Similarly, the spatial distributions of the laser radiation intensity were measured by replacing thermocouple with optical fiber probe. A thermal camera was used to control the temperature of the bone surface near the tip of the fiber. It was shown that the marrow could be heated from the outside by about 5-10°C during 10s without significant overheating of the bone tissue. The data obtained make it possible to estimate the volume of the bone marrow heated by the laser to a predetermined temperature and to make a reasonable choice of laser exposure modes to stimulate the proliferative activity of bone marrow mesenchymal stem cells in vivo.