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Animals : An Open Access Journal From... Mar 2024An 8-month-old male American Staffordshire terrier was referred for a no-weightbearing lameness of the right pelvic limb, hyperthermia, lethargy and inappetence. Two...
Use of a Custom-Made Patellar Groove Replacement in an American Staffordshire Terrier Puppy with a Severe Bone Defect in the Femoral Trochlea Caused by Hematogenous Osteomyelitis.
An 8-month-old male American Staffordshire terrier was referred for a no-weightbearing lameness of the right pelvic limb, hyperthermia, lethargy and inappetence. Two months before, endocarditis was diagnosed and treated in another veterinary hospital. Orthopedic, radiographic and tomographic examinations revealed a bone sequestrum of 4 × 1.4 cm and active periosteal reaction of the caudo-lateral cortical in the metaphysis and the distal third of the right femoral diaphysis, medullary osteolysis and interruption of the cranio-medial cortical profile, with involvement of the femoral trochlea leading to a secondary medial patella luxation. Hematogenous osteomyelitis was the suspected diagnosis. Once skeletally mature, after 4 months from surgical debridement and aggressive antibiotic therapy against Klebsiella oxytoca revealed by a bacteriological exam, the patient underwent prosthetic surgery for the application of a custom-made patellar groove replacement (PGR) to fill the bone defect and restore the femoral trochlea surface. Despite the serious injury that afflicted the right pelvic limb, the surgery had satisfactory outcomes until the last 18-month postoperative follow up.
PubMed: 38540007
DOI: 10.3390/ani14060909 -
Aging Mar 2024Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both and settings. Mitoquinone (MitoQ) is a selective...
Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both and settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species. To investigate the effect of long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice. Although we observed some beneficial effects of MB and MitoQ , the administration of these compounds did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 in UM-HET3 mice. Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.
Topics: Male; Female; Mice; Animals; Antioxidants; Methylene Blue; Mice, Inbred C57BL; Oxidative Stress; Aging; Mitochondrial Diseases; Organophosphorus Compounds; Ubiquinone
PubMed: 38535998
DOI: 10.18632/aging.205147 -
Annals of Joint 2023The aging population and the increasing number of patients with primary total hip arthroplasties (THA) has equated to an increased incidence of periprosthetic fractures... (Review)
Review
The aging population and the increasing number of patients with primary total hip arthroplasties (THA) has equated to an increased incidence of periprosthetic fractures (PPF) of the hip. These injuries are a significant source of patient morbidity and mortality, placing a financial burden on healthcare systems worldwide. As the volume of PPF is expected to along with the growing volume of primary and revision THA, it is important to understand the outcomes and factors associated with treatment success. The choice of procedure is in large part guided by the help of the Vancouver Classification system, which is a valid and reproducible system that classifies fractures based on several factors including site of fracture, implant stability and bone stock. PPFs account for approximately 18% of revision THA (rTHA) procedures. rTHA for PPFs is commonly indicated in Vancouver B2 and B3 fractures, to bypass a lack of metaphyseal support with diaphyseal fixation. Such revisions are technically challenging and typically require urgent treatment, with inherent difficulties in patient optimization, leading to a notable rate of post-operative complications, re-revision and mortality. This article reviews epidemiology, health economics and risk factors for PPFs. It additionally reviews outcomes associated with rTHA for PPFs including peri-operative complications, indications for re-operation, rates of re-operation and rates of mortality. Finally, it aims to identify evidence-based factors that have been associated with successful management including modifiable patient-related factors, uncemented cemented stems, stem design (porous coated stems fluted tapered stems), modularity, dislocation and its impact on outcomes following rTHA and strategies for managing bone loss.
PubMed: 38529253
DOI: 10.21037/aoj-23-16 -
International Orthopaedics Jul 2024Bone growth is a fascinating process, primarily due to its complexity. Equally engaging is the history of its study, which, however, remains unknown to most anatomists...
INTRODUCTION
Bone growth is a fascinating process, primarily due to its complexity. Equally engaging is the history of its study, which, however, remains unknown to most anatomists and surgeons.
MATERIALS AND METHODS
A literature search was performed in original publications and historical sources.
RESULTS
The early history of bone growth study may be divided into two periods. Firstly, the experimental one, between 1722 and 1847, which consisted in the study of bone growth by the drilling of benchmark holes into the diaphysis, and examination of growing bones in madder-fed animals. In the course of one century, four French scientists (Henri-Louis Duhamel du Monceau, Marie-Jean-Pierre Flourens, Gaspard Auguste Brullé and Frédéric Léopold Hugueny) and one British researcher (John Hunter) proved experimentally that the longitudinal growth of long bones occurred only at its epiphyseal ends and their final shape resulted from apposition and resorption processes taking place simultaneously both on the periosteal and intramedullary surfaces of the bone. In the second, the microscopic period (1836-1875), the physeal growth cartilage was discovered and described in detail, including its importance for the longitudinal growth of long bones. The first description of growth cartilage was published by a Swiss anatomist Miescher in 1836. Subsequently, this structure was studied by a number of English, German and French anatomists and surgeons. This whole period was concluded by Alfred Kölliker´s extensive study of bone resorption and its significance for typical bone shapes and Karl Langer´s study of the vascular supply of the growing and mature bone.
CONCLUSION
Research by French, English, German and Swiss scientists between 1727 and 1875 yielded fundamental insights into the growth of long bones, most of which are still valid today.
Topics: History, 19th Century; Bone Development; History, 18th Century; Humans; Animals
PubMed: 38528251
DOI: 10.1007/s00264-024-06157-w -
Bone Jun 2024Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as...
Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as intellectual disability and behavioral comorbidities, including autism and anxiety. Tatton-Brown-Rahman Syndrome is one type of overgrowth and intellectual disability disorder caused by heterozygous missense mutations in the DNA methyltransferase 3A (DNMT3A) gene. Numerous DNMT3A mutations have been identified in Tatton-Brown-Rahman Syndrome patients and may be associated with varying phenotype severities of clinical presentation. Two such mutations are the R882H and P904L mutations which result in severe and mild phenotypes, respectively. Mice with paralogous mutations (Dnmt3a and Dnmt3a) exhibit overgrowth in their long bones (e.g., femur, humerus), but the mechanisms responsible for their skeletal overgrowth remain unknown. The goal of this study is to characterize skeletal phenotypes in mouse models of Tatton-Brown-Rahman Syndrome and identify potential cellular mechanisms involved in the skeletal overgrowth phenotype. We report that mature mice with the Dnmt3a or Dnmt3a mutation exhibit tibial overgrowth, cortical bone thinning, and weakened bone mechanical properties. Dnmt3a mutants also contain larger bone marrow adipocytes while Dnmt3a mutants show no adipocyte phenotype compared to control animals. To understand the potential cellular mechanisms regulating these phenotypes, growth plate chondrocytes, osteoblasts, and osteoclasts were assessed in juvenile mutant mice using quantitative static histomorphometry and dynamic histomorphometry. Tibial growth plates appeared thicker in mutant juvenile mice, but no changes were observed in osteoblast activity or osteoclast number in the femoral mid-diaphysis. These studies reveal new skeletal phenotypes associated with Tatton-Brown-Rahman Syndrome in mice and provide a rationale to extend clinical assessments of patients with this condition to include bone density and quality testing. These findings may be also informative for skeletal characterization of other mouse models presenting with overgrowth and intellectual disability phenotypes.
Topics: Humans; Animals; Mice; DNA (Cytosine-5-)-Methyltransferases; Intellectual Disability; Mutation, Missense; DNA Methyltransferase 3A; Abnormalities, Multiple; Mutation; Musculoskeletal Abnormalities
PubMed: 38522809
DOI: 10.1016/j.bone.2024.117085 -
Experimental Gerontology May 2024Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the...
BACKGROUND
Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis.
METHODS
The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules.
RESULTS
The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing β-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction.
CONCLUSIONS
The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice.
Topics: Mice; Animals; Osteocytes; Ferroptosis; In Situ Hybridization, Fluorescence; NF-E2-Related Factor 2; Vitamin D; RNA, Messenger
PubMed: 38521178
DOI: 10.1016/j.exger.2024.112408 -
Cureus Feb 2024Scurvy is a disease caused by a lack of vitamin C. It is a nutritional deficiency that is associated with multiple severe conditions. Although developed countries report...
Scurvy is a disease caused by a lack of vitamin C. It is a nutritional deficiency that is associated with multiple severe conditions. Although developed countries report these cases rarely now due to advancements in food and nutritional supplements, they are still prevalent in developing countries, albeit rare, because of poor nutritional status. Due to the lower prevalence of scurvy, diagnosis is delayed in the majority of cases and sometimes missed completely, which results in serious complications and unnecessary workups. Here, we present a rare case of a four-year-old female child with severe acute malnutrition (SAM) presenting with scurvy. The initial clinical signs showed SAM. X-ray and MRI of the left femur and knee were done to further evaluate the orthopedic parameters. Clinical presentation and radiographic imaging confirmed all the signs of scurvy. The patient was started on the Formula 75 (F-75) diet to address the severe malnutrition, and steady weight gain was observed.
PubMed: 38516488
DOI: 10.7759/cureus.54506 -
Orthopaedic Journal of Sports Medicine Mar 2024Soft tissue plays an important role in stabilizing the hinge point for osteotomy around the knee. However, insufficient data are available on the anatomic features of...
BACKGROUND
Soft tissue plays an important role in stabilizing the hinge point for osteotomy around the knee. However, insufficient data are available on the anatomic features of the soft tissue around the hinge position for lateral closing-wedge distal femoral osteotomy (LCWDFO).
PURPOSE
To (1) anatomically analyze the soft tissue around the hinge position for LCWDFO, (2) histologically analyze the soft tissue based on the anatomic analysis results, and (3) radiologically define the appropriate hinge point to prevent unstable hinge fracture based on the results of the anatomic and histological analyses.
STUDY DESIGN
Descriptive laboratory study.
METHODS
In 20 cadaveric knees (age, 82.7 ± 7.8 years; range, 60-96 years), the soft tissue of the distal medial side of the femur was anatomically analyzed. The thicknesses of the periosteum and direct insertion of the adductor tendon (AT) were histologically examined and measured using an electron microscope. The thickness of the periosteum was visualized graphically, and the graph of the periosteum and radiograph of the knee were overlaid using image editing software. The appropriate hinge position was determined based on the periosteal thickness and attachment of the AT.
RESULTS
The mean thickness of the periosteum of the metaphysis was 352.7 ± 58.6 µm (range, 213.6-503.4 µm). The overlaid graph and radiograph revealed that the thickness of the periosteum changed at the part corresponding to the transition between the diaphyseal and metaphyseal ends of the femur. The mean width of the AT attached to the distal medial femur from the adductor tubercle toward the distal direction was 7.9 ± 1.3 mm (range, 6.3-9.7 mm).
CONCLUSION
Results indicated that the periosteum and AT support the hinge for LCWDFO within the area surrounded by the apex of the adductor tubercle and the upper border of the posterior part of the lateral femoral condyle.
CLINICAL RELEVANCE
When the hinge point is located within the area surrounded by the apex of the adductor tubercle and the upper border of the posterior part of the lateral femoral condyle, these soft tissues work as stabilizers, and there is no risk of cutting into the joint space.
PubMed: 38510318
DOI: 10.1177/23259671241233014 -
BMC Musculoskeletal Disorders Mar 2024Surgical treatment of irreducible distal radius diaphyseal- metaphyseal junction fractures involves difficulties as the fracture remains too proximal for K-wire fixation...
BACKGROUND
Surgical treatment of irreducible distal radius diaphyseal- metaphyseal junction fractures involves difficulties as the fracture remains too proximal for K-wire fixation and too distal for the elastic stable intramedullary nail. Our study aims to present the clinical results of applying an elastic stable intramedullary nail with a poller K-wire to achieve both reduction and stable fixation.
PATIENTS AND METHODS
A retrospective analysis was performed on 26 patients who underwent ESIN with a poller K-wire for distal radius diaphyseal-metaphyseal region fracture. Reduction parameters such as residual angulation and alignment were evaluated on postoperative follow-up radiographs. Changes in angular and alignment parameters on follow-up radiographs were recorded. Wrist and forearm functions were evaluated at the last follow-up.
RESULT
There were 17 male and nine female patients with an average age of 10.9. The residual angulation in coronal and sagittal planes on immediate postoperative radiographs was 4.0 ± 1.62° and 3.0 ± 1.26°, respectively. The mean translation rate on immediate postoperative radiographs was 6.0 ± 1.98% and 5.0 ± 2.02% in the coronal and sagittal planes, respectively. No change was observed in translation rates in the last follow-ups. The mean angulation in the coronal and sagittal planes measured on 6th-week radiographs was 4.0 ± 1.72°and 3.0 ± 1.16°, respectively. No significant difference was observed in angular changes in the sagittal and coronal planes at the last follow-up (p > 0.05). No tendon injury or neurovascular injury was observed in any of the patients.
CONCLUSION
In the surgical treatment of pediatric DRDMJ fractures, applying ESIN with poller K-wire is an effective, safe, and novel method for achieving reduction and stable fixation.
Topics: Humans; Child; Male; Female; Retrospective Studies; Radius; Fracture Fixation, Intramedullary; Bone Wires; Radius Fractures; Treatment Outcome; Bone Nails
PubMed: 38509566
DOI: 10.1186/s12891-024-07358-5 -
Biological & Pharmaceutical Bulletin 2024Osteoporosis is caused by imbalance between osteogenesis and bone resorption, thus, osteogenic drugs and resorption inhibitors are used for treatment of osteoporosis....
Osteoporosis is caused by imbalance between osteogenesis and bone resorption, thus, osteogenic drugs and resorption inhibitors are used for treatment of osteoporosis. The present study examined the effects of (R)-4-(1-hydroxyethyl)-3-{4-[2-(tetrahydropyran-4-yloxy)ethoxy]phenoxy}benzamide (KY-273), a diphenyl ether derivative, on CDK8/19 activity, osteoblast differentiation and femoral bone using micro-computed tomography in female rats. KY-273 potently inhibited CDK8/19 activity, promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity, and gene expression of type I collagen, ALP and BMP-4 in mesenchymal stem cells (ST2 cells). In female rat femur, ovariectomy decreased metaphyseal trabecular bone volume (Tb.BV), mineral content (Tb.BMC), yet had no effect on metaphyseal and diaphyseal cortical bone volume (Ct.BV), mineral content (Ct.BMC) and strength parameters (BSPs). In ovaries-intact and ovariectomized rats, oral administration of KY-273 (10 mg/kg/d) for 6 weeks increased metaphyseal and diaphyseal Ct.BV, Ct.BMC, and BSPs without affecting medullary volume (Med.V), but did not affect Tb.BV and Tb.BMC. In ovariectomized rats, alendronate (3 mg/kg/d) caused marked restoration of Tb.BV, Tb.BMC and structural parameters after ovariectomy, and increased metaphyseal but not diaphyseal Ct.BV, Ct.BMC, and BSPs. In ovaries-intact and ovariectomized rats, by the last week, KY-273 increased bone formation rate/bone surface at the periosteal but not the endocortical side. These findings indicate that KY-273 causes osteogenesis in cortical bone at the periosteal side without reducing Med.V. In conclusion, KY-273 has cortical-bone-selective osteogenic effects by osteoblastogenesis via CDK8/19 inhibition in ovaries-intact and ovariectomized rats, and is an orally active drug candidate for bone diseases such as osteoporosis in monotherapy and combination therapy.
Topics: Humans; Rats; Female; Animals; Osteogenesis; Bone Density; Rats, Sprague-Dawley; X-Ray Microtomography; Osteoporosis; Ovariectomy; Mesenchymal Stem Cells; Minerals; Cyclin-Dependent Kinase 8
PubMed: 38508765
DOI: 10.1248/bpb.b23-00834