RESUMEN
BACKGROUND: Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. METHODS: To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. RESULTS: TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.
TTT accelerates wound healing in diabetic rabbit instep ulcers, with both unilateral and bilateral surgeries effective, and bilateral TTT showing enhanced efficacy.TTT boosts angiogenesis and collagen fiber formation, leading to increased granulation tissue and re-epithelialization of wounds.TTT induces the mobilization and homing of endothelial progenitor cells to promote angiogenesis and wound healing.
Asunto(s)
Pie Diabético , Células Progenitoras Endoteliales , Neovascularización Fisiológica , Cicatrización de Heridas , Animales , Pie Diabético/terapia , Pie Diabético/fisiopatología , Pie Diabético/patología , Conejos , Células Progenitoras Endoteliales/metabolismo , Tibia/patología , Modelos Animales de Enfermedad , Masculino , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/fisiopatología , Movimiento CelularRESUMEN
Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy. Building upon prior findings that i) Yoda1, the Piezo1 agonist, promoted bone growth in young adult mice and suppressed bone resorption markers in aged mice, and ii) moderate tibial loading protected bone from breast cancer-induced osteolysis, we hypothesized that combined Yoda1 and moderate loading would improve the structural integrity of adult and aged skeletons in vivo and protect bones from deterioration after chemotherapy. We first examined the effects of 4-week Yoda1 (dose 5 mg/kg, 5 times/week) and moderate tibial loading (4.5 N peak load, 4 Hz, 300 cycles for 5 days/week), individually and combined, on mature mice (â¼50 weeks of age). Combined Yoda1 and loading was found to mitigate age-associated cortical and trabecular bone loss better than individual interventions. As expected, the non-treated controls experienced an average drop of cortical polar moment of inertia (Ct.pMOI) by -4.3 % over four weeks and the bone deterioration occurred in the majority (64 %) of the samples. Relative to no treatment, loading alone, Yoda1 alone, and combined Yoda1 and loading increased Ct.pMOI by +7.3 %, +9.5 %, +12.0 % and increased the % of samples with positive Ct.pMOI changes by +32 %, +26 %, and +43 %, respectively, suggesting an additive protection of aging-related bone loss for the combined therapy. We further tested if the treatment efficacy was preserved in mature mice following two weeks (six injections) of doxorubicin at the dose of 2.5 or 5 mg/kg. As expected, doxorubicin increased osteocyte apoptosis, altered bone remodeling, and impaired bone structure. However, the effects induced by DOX were too severe to be rescued by Yoda1 and loading, alone or combined, although loading and Yoda1 individually, or combined, increased the number of mice showing positive responsiveness by 0 %, +15 %, and +29 % relative to no intervention after doxorubicin exposure. Overall, this study supported the potentials and challenges of the Yoda1-based strategy in mitigating the detrimental skeletal effects caused by aging and doxorubicin.
Asunto(s)
Envejecimiento , Doxorrubicina , Animales , Doxorrubicina/efectos adversos , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Femenino , Ratones , Tibia/efectos de los fármacos , Tibia/diagnóstico por imagen , Tibia/patología , Resorción Ósea/patología , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/inducido químicamente , Ratones Endogámicos C57BL , Fenómenos Biomecánicos/efectos de los fármacos , Microtomografía por Rayos X , Biofisica , Tiofenos/farmacologíaRESUMEN
Hepatocellular carcinoma (HCC), sixth most common cancer world-over, commonly metastasizes to lung, lymph nodes and adrenal glands. Incidence of osseous metastases in HCC has been reported to be 3-20 % which occurs predominantly in the axial skeleton. It only rarely occurs in the appendicular skeleton and that too as the solitary focus of metastatic deposit.3,4 We present a case of HCC with solitary osseous metastases to the proximal tibia.
Asunto(s)
Neoplasias Óseas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Tibia , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/secundario , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Óseas/secundario , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Masculino , Tibia/diagnóstico por imagen , Tibia/patología , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Persona de Mediana EdadRESUMEN
INTRODUCTION: Growth plate damage in long bones often results in progressive skeletal growth imbalance and deformity, leading to significant physical problems. Gangliosides, key glycosphingolipids in cartilage, are notably abundant in articular cartilage and regulate chondrocyte homeostasis. This suggests their significant roles in regulating growth plate cartilage repair. METHODS: Chondrocytes from 3 to 5 day-old C57BL/6 mice underwent glycoblotting and mass spectrometry. Based on the results of the glycoblotting analysis, we employed GD3 synthase knockout mice (GD3-/-), which lack b-series gangliosides. In 3-week-old mice, physeal injuries were induced in the left tibiae, with right tibiae sham operated. Tibiae were analyzed at 5 weeks postoperatively for length and micro-CT for growth plate height and bone volume at injury sites. Tibial shortening ratio and bone mineral density were measured by micro-CT. RESULTS: Glycoblotting analysis indicated that b-series gangliosides were the most prevalent in physeal chondrocytes among ganglioside series. At 3 weeks, GD3-/- exhibited reduced tibial shortening (14.7 ± 0.2 mm) compared to WT (15.0 ± 0.1 mm, P = 0.03). By 5 weeks, the tibial lengths in GD3-/- (16.0 ± 0.4 mm) closely aligned with sham-operated lengths (P = 0.70). Micro-CT showed delayed physeal bridge formation in GD3-/-, with bone volume measuring 168.9 ± 5.8 HU at 3 weeks (WT: 180.2 ± 3.2 HU, P = 0.09), but normalizing by 5 weeks. CONCLUSION: This study highlights that GD3 synthase knockout mice inhibit physeal bridge formation after growth plate injury, proposing a new non-invasive approach for treating skeletal growth disorders.
Asunto(s)
Condrocitos , Gangliósidos , Placa de Crecimiento , Ratones Endogámicos C57BL , Ratones Noqueados , Animales , Placa de Crecimiento/patología , Placa de Crecimiento/metabolismo , Gangliósidos/metabolismo , Condrocitos/metabolismo , Ratones , Diferencia de Longitud de las Piernas , Tibia/diagnóstico por imagen , Tibia/patología , Tibia/metabolismo , Tibia/crecimiento & desarrollo , Microtomografía por Rayos X , Sialiltransferasas/deficiencia , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Modelos Animales de EnfermedadRESUMEN
Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model. Based upon the rapid reduction of bone formation and initial elevation of resorption caused by GCs, we hypothesized that the rate of advance (longitudinal erosion rate; LER) of cortical BMUs would be increased. To test this hypothesis we divided 20 female New Zealand White rabbits into four experimental groups: ovariohysterectomy (OVH), glucocorticoid (GC), OVH + GC and SHAM controls (n = 5 animals each). Ten weeks post-surgery (OVH or sham), and two weeks after the initiation of dosing (daily subcutaneous injections of 1.5 mg/kg of methylprednisolone sodium succinate in the GC-treated groups and 1 ml of saline for the others), the right tibiae were scanned in vivo using Synchrotron Radiation (SR) in-line phase contrast micro-CT at the Canadian Light Source. After an additional 2 weeks of dosing, the rabbits were euthanized and ex vivo images were collected using desktop micro-CT. The datasets were co-registered in 3D and LER was calculated as the distance traversed by BMU cutting-cones in the 14-day interval between scans. Counter to our hypothesis, LER was greatly reduced in GC-treated rabbits. Mean LER was lower in GC (4.27 µm/d; p < 0.001) and OVH + GC (4.19 µm/d; p < 0.001), while similar in OVH (40.13 µm/d; p = 0.990), compared to SHAM (40.44 µm/d). This approximately 90 % reduction in LER with GCs was also associated with an overall disruption of BMU progression, with radial expansion of the remodeling space occurring in all directions. This unexpected outcome suggests that GCs do not simply uncouple formation and resorption within cortical BMUs and highlights the value of the time-lapsed 4D approach employed.
Asunto(s)
Hueso Cortical , Glucocorticoides , Tibia , Microtomografía por Rayos X , Animales , Conejos , Glucocorticoides/farmacología , Femenino , Tibia/efectos de los fármacos , Tibia/diagnóstico por imagen , Tibia/patología , Hueso Cortical/efectos de los fármacos , Hueso Cortical/diagnóstico por imagen , Remodelación Ósea/efectos de los fármacosRESUMEN
We present a case detailing the diagnosis and management of a periprosthetic giant cell tumour in a female patient in her 70s, who had undergone total knee arthroplasty (TKA) for primary osteoarthritis in her right knee 7 years prior. The patient reported 4 months of painful weight-bearing. Various imaging modalities, including plain radiographs, CT scans and MRI, revealed a sizeable lytic lesion beneath the TKA prosthesis, along with loosening of the tibial component.Blood tests and analyses of synovial fluid ruled out periprosthetic joint infection, and a biopsy confirmed the diagnosis of a giant cell tumour of the bone. Treatment entailed en bloc resection of the tumour and revision of the TKA using a hinged, oncological-type megaprosthesis. Surgical procedures involved careful resection of the proximal tibia, preservation of vasculature and the creation of a medial gastrocnemius muscle flap. Following surgery, the patient underwent supervised rehabilitation with a functional brace.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Neoplasias Óseas , Tumor Óseo de Células Gigantes , Prótesis de la Rodilla , Reoperación , Tibia , Humanos , Femenino , Tibia/cirugía , Tibia/patología , Tibia/diagnóstico por imagen , Artroplastia de Reemplazo de Rodilla/métodos , Tumor Óseo de Células Gigantes/cirugía , Tumor Óseo de Células Gigantes/patología , Tumor Óseo de Células Gigantes/diagnóstico por imagen , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Anciano , Falla de PrótesisRESUMEN
Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients with CPT are affected by the multisystemic genetic disorder neurofibromatosis type 1 (NF1) caused by mutations in the NF1 tumor suppressor gene, a negative regulator of RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Here, we analyzed patients with CPT and Prss56-Nf1 knockout mice to elucidate the pathogenic mechanisms of CPT-related fibrous nonunion and explored a pharmacological approach to treat CPT. We identified NF1-deficient Schwann cells and skeletal stem/progenitor cells (SSPCs) in pathological periosteum as affected cell types driving fibrosis. Whereas NF1-deficient SSPCs adopted a fibrotic fate, NF1-deficient Schwann cells produced critical paracrine factors including transforming growth factor-ß and induced fibrotic differentiation of wild-type SSPCs. To counteract the elevated RAS-MAPK signaling in both NF1-deficient Schwann cells and SSPCs, we used MAPK kinase (MEK) and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Combined MEK-SHP2 inhibition in vivo prevented fibrous nonunion in the Prss56-Nf1 knockout mouse model, providing a promising therapeutic strategy for the treatment of fibrous nonunion in CPT.
Asunto(s)
Ratones Noqueados , Neurofibromina 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Seudoartrosis , Células de Schwann , Animales , Femenino , Humanos , Masculino , Ratones , Diferenciación Celular/efectos de los fármacos , Fibrosis , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Neurofibromatosis 1/patología , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/complicaciones , Neurofibromina 1/metabolismo , Neurofibromina 1/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/antagonistas & inhibidores , Seudoartrosis/patología , Seudoartrosis/metabolismo , Seudoartrosis/congénito , Células de Schwann/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/patología , Células Madre/metabolismo , Células Madre/efectos de los fármacos , Tibia/patologíaRESUMEN
We evaluated the potential of sclerostin antibody (SclAb) therapy to enhance osseointegration of dental and orthopaedic implants in a mouse model (Brtl/+) mimicking moderate to severe Osteogenesis Imperfecta (OI). To address the challenges in achieving stable implant integration in compromised bone conditions, our aim was to determine the effectiveness of sclerostin antibody (SclAb) at improving bone-to-implant contact and implant fixation strength. Utilizing a combination of micro-computed tomography, mechanical push-in testing, immunohistochemistry, and Western blot analysis, we observed that SclAb treatment significantly enhances bone volume fraction (BV/TV) and bone-implant contact (BIC) in Brtl/+ mice, suggesting a normalization of bone structure toward WT levels. Despite variations in implant survival rates between the maxilla and tibia, SclAb treatment consistently improved implant stability and resistance to mechanical forces, highlighting its potential to overcome the inherent challenges of OI in dental and orthopaedic implant integration. These results suggest that SclAb could be a valuable therapeutic approach for enhancing implant success in compromised bone conditions.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Anticuerpos , Colágeno Tipo I , Mutación , Oseointegración , Animales , Oseointegración/efectos de los fármacos , Ratones , Mutación/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Anticuerpos/farmacología , Microtomografía por Rayos X , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Huesos/patología , Péptidos y Proteínas de Señalización Intercelular , Implantes Dentales , Tibia/diagnóstico por imagen , Tibia/patología , Tibia/efectos de los fármacosRESUMEN
Background: Osteoarthritis (OA) is a degenerative disease requiring additional research. This study compared gene expression and immune infiltration between lesioned and preserved subchondral bone. The results were validated using multiple tissue datasets and experiments. Methods: Differentially expressed genes (DEGs) between the lesioned and preserved tibial plateaus of OA patients were identified in the GSE51588 dataset. Moreover, functional annotation and protein-protein interaction (PPI) network analyses were performed on the lesioned and preserved sides to explore potential therapeutic targets in OA subchondral bones. In addition, multiple tissues were used to screen coexpressed genes, and the expression levels of identified candidate DEGs in OA were measured by quantitative real-time polymerase chain reaction. Finally, an immune infiltration analysis was conducted. Results: A total of 1,010 DEGs were identified, 423 upregulated and 587 downregulated. The biological process (BP) terms enriched in the upregulated genes included "skeletal system development", "sister chromatid cohesion", and "ossification". Pathways were enriched in "Wnt signaling pathway" and "proteoglycans in cancer". The BP terms enriched in the downregulated genes included "inflammatory response", "xenobiotic metabolic process", and "positive regulation of inflammatory response". The enriched pathways included "neuroactive ligand-receptor interaction" and "AMP-activated protein kinase signaling". JUN, tumor necrosis factor α, and interleukin-1ß were the hub genes in the PPI network. Collagen XI A1 and leucine-rich repeat-containing 15 were screened from multiple datasets and experimentally validated. Immune infiltration analyses showed fewer infiltrating adipocytes and endothelial cells in the lesioned versus preserved samples. Conclusion: Our findings provide valuable information for future studies on the pathogenic mechanism of OA and potential therapeutic and diagnostic targets.
Asunto(s)
Mapas de Interacción de Proteínas , Humanos , Perfilación de la Expresión Génica , Osteoartritis/genética , Osteoartritis/inmunología , Osteoartritis/patología , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/inmunología , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/metabolismo , Masculino , Tibia/patología , Tibia/inmunología , Tibia/metabolismo , Regulación hacia Abajo , FemeninoRESUMEN
BACKGROUND: The purpose of this study was to clarify (1) the differences in cortical bone thickness (CBT) of the tibial diaphysis between healthy and osteoarthritic knees and (2) the influences of the femorotibial angle (FTA) and inclination of the medial compartment of the proximal tibia (MCT) on tibial CBT. METHODS: The study assessed 60 subjects with varus knee osteoarthritis (OA) (22 males and 38 females; mean age, 74 ± 7 years) and 53 healthy elderly subjects (28 males and 25 females; mean age, 70 ± 6 years). Three-dimensional estimated CBT of the tibial diaphysis was automatically calculated for 2752-11,296 points using high-resolution measurements from CT. The standardized CBT was assessed in 24 regions by combining six heights and four areas. Additionally, the association between the CBT, each FTA, and MCT inclination was investigated. RESULTS: The OA group showed a thicker CBT in the medial areas than in the lateral areas of the proximal tibia, while the healthy group had a thicker lateral CBT. The medial-to-lateral ratio of the proximal tibia was significantly higher in the OA group than in the healthy group. The proximal-medial CBT correlated with FTA and MCT inclinations in the OA group. CONCLUSIONS: This study demonstrated that varus osteoarthritic knees showed a different trend of proximal-medial CBT with associations in FTA and MCT inclination from healthy knees, possibly due to medial load concentration.
Asunto(s)
Hueso Cortical , Diáfisis , Osteoartritis de la Rodilla , Tibia , Humanos , Masculino , Femenino , Tibia/diagnóstico por imagen , Tibia/patología , Anciano , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/patología , Diáfisis/diagnóstico por imagen , Diáfisis/patología , Anciano de 80 o más Años , Tomografía Computarizada por Rayos X , Extremidad Inferior/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
Significant alterations to subchondral trabecular bone microarchitecture are observed in late-stage osteoarthritis (OA). However, detailed investigation of these changes to bone in the ankle are under-reported. This study aimed to fully characterise the trabecular morphology in OA ankle bone specimens compared to non-diseased (ND) controls using both standard and individual-trabecular segmentation-based (ITS) analyses. Ten ND tibial bone specimens were extracted from three cadaveric ankles, as well as five OA bone specimens from patients undergoing total ankle arthroplasty surgery. Each specimen was scanned using microcomputed tomography from which a 4 mm cuboidal volume was extracted for analysis. Morphological parameters for the subchondral trabecular bone were measured using BoneJ (NIH ImageJ) and 3D ITS for whole volumes and at each depth level in 1 mm increments. The results show an overall increase in bone volume fraction (p<0.01) and trabecular thickness (p<0.001) with OA, with a decrease in anisotropy (p<0.05). ITS analysis showed OA bone was composed of more rod-like trabeculae and plate-like trabeculae compared to ND bone. Numerous properties were depth dependent, but the results demonstrated that towards the subchondral bone plate, both rod- and plate-like trabeculae were thicker, rods were longer and plates had increased surface area. Overall, this study has verified key microstructural alterations to ankle subchondral bone that are found in other OA lower-limb joints. Depth-based analysis has highlighted differences of interest for further evaluation into the remodelling mechanisms that occur with OA, which is critical to understanding the role of subchondral bone microarchitecture in the progression of the disease.
Asunto(s)
Articulación del Tobillo , Osteoartritis , Tibia , Microtomografía por Rayos X , Humanos , Osteoartritis/patología , Osteoartritis/diagnóstico por imagen , Femenino , Anciano , Masculino , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/patología , Persona de Mediana Edad , Tibia/patología , Tibia/diagnóstico por imagen , Hueso Esponjoso/patología , Hueso Esponjoso/diagnóstico por imagen , Anciano de 80 o más AñosRESUMEN
Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (40.43%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone-targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications.
Asunto(s)
Alendronato , Neoplasias Óseas , Nanopartículas , Osteólisis , Tibia , Alendronato/administración & dosificación , Alendronato/farmacocinética , Alendronato/química , Animales , Osteólisis/prevención & control , Osteólisis/tratamiento farmacológico , Femenino , Nanopartículas/química , Nanopartículas/administración & dosificación , Tibia/efectos de los fármacos , Tibia/patología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Porosidad , Línea Celular Tumoral , Humanos , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacocinética , Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/farmacocinética , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Ratones Endogámicos BALB C , Ratones , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patologíaRESUMEN
SummaryGiant cell tumours of bone are benign and locally aggressive tumours that usually occur in young adults and at the epiphysial locations after physeal closure. Occurrence outside of epiphysial locations and appearance in geriatric patients is rare. We report a case of a woman in her late 60s with a giant cell tumour of the mid-shaft of the right tibia. Extended curettage and biological reconstruction were performed with autologous double-barrel fibular struts and tri-cortical iliac crest bone grafting. At the 28-month follow-up examination, we noted full bony union at both ends with successful consolidation of the fibular struts, and importantly, no evidence of recurrence or other complications was observed.
Asunto(s)
Neoplasias Óseas , Tumor Óseo de Células Gigantes , Tibia , Humanos , Femenino , Tibia/diagnóstico por imagen , Tibia/cirugía , Tibia/patología , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Neoplasias Óseas/diagnóstico por imagen , Tumor Óseo de Células Gigantes/cirugía , Tumor Óseo de Células Gigantes/patología , Tumor Óseo de Células Gigantes/diagnóstico por imagen , Legrado , Trasplante Óseo/métodos , Persona de Mediana Edad , Ilion/diagnóstico por imagen , Peroné/diagnóstico por imagen , Peroné/patología , Peroné/cirugía , Diáfisis/cirugía , Resultado del TratamientoRESUMEN
We present a novel case of a malignant transformation of an extremity soft tissue angioleiomyoma to leiomyosarcoma in a man in his late 70s who presented with a painful and increasing lump on his anterior tibia. Initial imaging and biopsy showed a benign angioleiomyoma which was excised for symptomatic reasons. An analysis of the resulting specimen revealed a 50×42×15 mm smooth muscle neoplasm consistent with angioleiomyoma with a 22×11 mm entirely intralesional nodular component in keeping with a grade 1 leiomyosarcoma. The malignant constituent of the lesion was entirely encased in benign angioleiomyoma negating the need for further surgery. Systemic staging investigation revealed no evidence of metastatic disease spread final staging as per the eighth edition of the American Joint Committee on Cancer (AJCC) Staging T1N0M0 R0 Stage 1 a.
Asunto(s)
Angiomioma , Leiomiosarcoma , Tibia , Humanos , Masculino , Leiomiosarcoma/patología , Leiomiosarcoma/cirugía , Leiomiosarcoma/diagnóstico por imagen , Tibia/patología , Tibia/diagnóstico por imagen , Angiomioma/patología , Angiomioma/cirugía , Angiomioma/diagnóstico por imagen , Anciano , Transformación Celular Neoplásica/patología , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Biopsia , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Neoplasias Óseas/diagnóstico por imagenRESUMEN
PURPOSE: Managing the distal tibiofibular (DTF) joint remains a challenge despite recent developments. Ankle arthroscopy is emerging as a diagnostic and therapeutic means. Our study aimed to compare preoperative imaging data and arthroscopic data, with the hypothesis that imaging alone is insufficient to evaluate acute laxity, and with arthroscopy as the reference examination. METHODS: All patients treated in 2023 in our department for an acute isolated DTF lesion were included prospectively. Preoperative radiographic and MRI imaging were compared with arthroscopic data. RESULTS: Ten patients were treated. For five patients, the instability was doubtful after carrying out an appropriate imaging assessment (X-rays of both ankles, MRI). For four of these five patients, instability was confirmed by arthroscopy. Arthroscopy was useful for suturing the anterior bundle of the DTF joint for two patients and allowed for verifying the reduction in the sagittal and coronal planes for two patients. No complications were detected. CONCLUSIONS: Arthroscopy in isolated acute DTF lesions seems to provide a diagnostic and therapeutic advantage. Its use may allow for exhaustive assessment and complete repair of lesions. It must be offered as soon as possible; a delay in specialized imaging may delay therapeutic care.
Asunto(s)
Articulación del Tobillo , Artroscopía , Inestabilidad de la Articulación , Imagen por Resonancia Magnética , Humanos , Artroscopía/métodos , Masculino , Femenino , Adulto , Articulación del Tobillo/cirugía , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/patología , Imagen por Resonancia Magnética/métodos , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/diagnóstico por imagen , Estudios Prospectivos , Persona de Mediana Edad , Adulto Joven , Traumatismos del Tobillo/cirugía , Traumatismos del Tobillo/diagnóstico , Traumatismos del Tobillo/diagnóstico por imagen , Peroné/cirugía , Peroné/diagnóstico por imagen , Resultado del Tratamiento , Radiografía/métodos , Adolescente , Tibia/cirugía , Tibia/diagnóstico por imagen , Tibia/patologíaRESUMEN
Distal femoral osteotomy (DFO) is performed alone or with high tibial osteotomy (HTO) for patients with osteoarthritis and distal femur deformities. DFO is technically demanding, particularly when creating an anterior flange. Herein, we examined the morphological characteristics of the distal femur based on the cortical shape as a surgical reference for biplanar DFO. Computed tomography images of 50 valgus and 50 varus knees of patients who underwent biplanar DFO or total knee arthroplasty were analyzed. Axial slices at the initial level of the transverse osteotomy in the DFO and slices 10 mm proximal and 10 mm distal to that level were selected. The medial and lateral cortical angles and heights (MCLA, LCLA, MCH, and LCH) were measured on axial slices. Statistical comparisons were performed between the medial and lateral cortices and valgus and varus knees. MCLA and MCH were significantly smaller and lower, respectively, than LCLA and LCH (P < 0.01). The MCLA and MCH of varus knees were significantly smaller and lower, respectively, than those of valgus knees (P < 0.01). Surgeons should carefully observe morphological differences in the distal femur cortex, distinguishing between medial and lateral knees and varus and valgus knees during the creation of the anterior flange in the DFO.
Asunto(s)
Fémur , Osteotomía , Tomografía Computarizada por Rayos X , Humanos , Osteotomía/métodos , Fémur/cirugía , Fémur/diagnóstico por imagen , Fémur/anatomía & histología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Artroplastia de Reemplazo de Rodilla/métodos , Tibia/cirugía , Tibia/diagnóstico por imagen , Tibia/anatomía & histología , Tibia/patología , AdultoRESUMEN
Subchondral bone remodeling, mediated by osteocytes within the lacuno-canalicular network, plays a crucial role in osteoarthritis (OA) progression. Following cell death, lacunae preserve integrity, offering insights into bone remodeling mechanisms. Limited and controversial data on osteocyte lacuna morphology in OA result from small sample sizes and two-dimensional (2D) techniques that have been used thus far. This study aimed to quantify three-dimensional (3D) osteocyte lacunar characteristics at well-defined tibial plateau locations, known to be differently affected by OA. Specifically, 11 tibial plateaus were obtained from end-stage knee-OA patients with varus deformity. Each plateau provided one sample from the less affected lateral compartment and two samples from the medial compartment, at minimum and maximum bone volume fraction (BV/TV) locations. High-resolution desktop micro-computed tomography (micro-CT) at 0.7 µm voxel resolution imaged the 33 samples. Lacuna number density (Lc.N/BV) and lacuna volume density (Lc.TV/BV) were significantly lower (p < 0.02) in samples from the medial side with maximum BV/TV compared to lateral side samples. In the medial compartment at maximum local BV/TV, mean lacuna volume (Lc.V), total lacuna volume (Lc.TV), and Lc.TV/BV were significantly (p < 0.001) lower than in the region with minimum BV/TV. Lc.N/BV was also significantly lower (p < 0.02) at the maximum local BV/TV location compared to the region with minimum BV/TV. Our findings suggest that subchondral bone lacunae adapt to the changing loads in end-stage OA.
Asunto(s)
Remodelación Ósea , Osteoartritis de la Rodilla , Osteocitos , Tibia , Microtomografía por Rayos X , Humanos , Osteocitos/patología , Tibia/patología , Tibia/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/diagnóstico por imagen , Masculino , Anciano , Femenino , Persona de Mediana Edad , Microtomografía por Rayos X/métodos , Remodelación Ósea/fisiologíaRESUMEN
OBJECTIVE: Understanding gender-specific differences in patterns of cartilage loss can improve our knowledge of the pathogenesis of knee osteoarthritis (KOA) development and progression and may inform clinical trials of treatments for KOA. The goal of our observational study was to examine gender differences in patterns of cartilage loss in the central weight-bearing regions of the femur. METHODS: We measured cartilage volume change in the indexed knee of 700 subjects with Kellgren-Lawrence 1, 2, or 3 from the Osteoarthritis Initiative for four follow-up periods (baseline [BL] to 24 mo, BL to 48 mo, BL to 72 mo, and BL to 96 mo) using the local area cartilage segmentation (LACS) method. Briefly, the LACS method uses robust coordinate systems fixed to anatomical landmarks to measure patterns of change in cartilage volume in sub-regions using responsiveness heat maps. RESULTS: We observed a statistically significant gender difference in cartilage change in the medial femur (MF), lateral femur (LF), and medial tibia. The heat maps showed loss was primarily in the posterior central weight-bearing portion of the LF and more general in the LT and MF. Similar patterns were observed for each of the four follow-up periods. CONCLUSIONS: The LACS method was capable of illustrating gender-specific differences in patterns of cartilage loss that may offer insight into the variation of gender differences in the natural history of KOA and may be useful in evaluating the benefit of interventions for KOA.
Asunto(s)
Cartílago Articular , Fémur , Osteoartritis de la Rodilla , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Cartílago Articular/patología , Cartílago Articular/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Fémur/patología , Fémur/diagnóstico por imagen , Factores Sexuales , Imagen por Resonancia Magnética , Soporte de Peso/fisiología , Articulación de la Rodilla/patología , Progresión de la Enfermedad , Tibia/patología , Caracteres SexualesRESUMEN
Bone tissue is subjected to increased mechanical stress during high-intensity work. Inadequate bone remodeling reparability can result in the continuous accumulation of microdamage, leading to stress fractures. The aim of this work was to investigate the characteristics and repair mechanisms of tibial microdamage under several degrees of overload. Also, we aimed at better understanding the effects of overload on the multi-scale structure and mechanical properties of bone. Sixty 5-month female rats were divided into three groups with different time points. Micro-CT was used to evaluate the three-dimensional microstructure, and three-point bending, quasi-static fracture toughness and creep mechanical test were carried out to evaluate the mechanical properties. SEM was used to observe the morphological characteristics of fracture surfaces. Section staining was used to count the microdamage parameters and numbers of osteoblasts and osteoclasts. The microarchitectures of cancellous and cortical bones in the three overload groups showed different degrees of damage. Overload led to a messy crystal structure of cortical bone, with slender microcracks mixed in, and a large number of broken fibers of cancellous bone. The properties associated with the elastic plasticity, fracture toughness, and viscoelasticity of cortical bone reduced in three groups, with that corresponding to day 30 presenting the highest damage. The accumulation of microdamage mainly occurred in the first 14 days, that is, the crack density peaked on day 14. Peak-targeted bone remodeling of cortical and cancellous bones occurred mainly between days 14 and 30. The influence of overload mechanical environment on bone quality at different time points was deeply investigated, which is of great significance for the etiology and treatment of stress fractures.