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Developmental Dynamics : An Official... Sep 2022The development of the vertebrate limb skeleton requires a complex interaction of multiple factors to facilitate the correct shaping and positioning of bones and joints....
BACKGROUND
The development of the vertebrate limb skeleton requires a complex interaction of multiple factors to facilitate the correct shaping and positioning of bones and joints. Growth and differentiation factor 5 (Gdf5) is involved in patterning appendicular skeletal elements including joints. Expression of gdf5 in zebrafish has been detected in fin mesenchyme condensations and segmentation zones as well as the jaw joint, however, little is known about the functional role of Gdf5 outside of Amniota.
RESULTS
We generated CRISPR/Cas9 knockout of gdf5 in zebrafish and analyzed the resulting phenotype at different developmental stages. Homozygous gdf5 mutant zebrafish displayed changes in segmentation of the endoskeletal disc and, as a consequence, loss of posterior radials in the pectoral fins. Mutant fish also displayed disorganization and reduced length of endoskeletal elements in the median fins, while joints and mineralization seemed unaffected.
CONCLUSIONS
Our study demonstrates the importance of Gdf5 in the development of the zebrafish pectoral and median fin endoskeleton and reveals that the severity of the effect increases from anterior to posterior elements. Our findings are consistent with phenotypes observed in the human and mouse appendicular skeleton in response to Gdf5 knockout, suggesting a broadly conserved role for Gdf5 in Osteichthyes.
Topics: Animal Fins; Animals; Bone and Bones; Gene Expression Regulation, Developmental; Growth Differentiation Factor 5; Mice; Zebrafish; Zebrafish Proteins
PubMed: 34242444
DOI: 10.1002/dvdy.399 -
Frontiers in Endocrinology 2022Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to...
Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water-Fat MRI.
Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22-75 years; 14 female: mean age 50 years, range 29-71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water-fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.
Topics: Adipose Tissue; Animals; Bone Marrow; Bone and Bones; Cross-Sectional Studies; Female; Humans; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Water
PubMed: 35574007
DOI: 10.3389/fendo.2022.815835 -
European Journal of Radiology Aug 2022To describe the appearances of bone marrow in the appendicular skeleton on fat-suppressed T2-weighted sequences as assessed by whole-body MRI in healthy and asymptomatic...
OBJECTIVE
To describe the appearances of bone marrow in the appendicular skeleton on fat-suppressed T2-weighted sequences as assessed by whole-body MRI in healthy and asymptomatic children and adolescents.
MATERIAL AND METHODS
Following ethical approval, we assessed the bone marrow of the extremities on water-only Dixon T2-weighted images as part of a whole-body MRI in 196 healthy and asymptomatic children aged 5-19 years. Based on a newly devised and validated scoring system, we graded intensity (0-2 scale) and extension (1-4 scale) of focal high signal bone marrow areas, and divided them into minor or major findings, based on intensity and extension, reflecting their potential conspicuousness in a clinical setting.
RESULTS
In the upper extremity, we registered 366 areas with increased signal whereof 79 were major findings. In the lower extremities there were 675 areas of increased signal of which 340 were major findings. Hundred-and-fifteen (58.79%) individuals had at least one major finding, mainly located in the hand and proximal humerus, and the feet and knees. We found no differences according to gender, reported hours of sports activity, handedness, or age group, except for more minor findings in the upper extremities amongst 15-18-year-olds as compared to those aged 5-8 years.
CONCLUSION
Focal areas of high signal intensity on whole-body MRI, T2-weighted fat suppressed images that, in a clinical setting could cause concern, were seen in more than half of healthy, asymptomatic children and adolescents. Awareness of this is important when interpreting whole-body MRI in this age group, particularly in the assessment of clinically silent lesions.
Topics: Adolescent; Bone Marrow; Child; Foot; Humans; Humerus; Magnetic Resonance Imaging; Whole Body Imaging
PubMed: 35617871
DOI: 10.1016/j.ejrad.2022.110365 -
Journal of Orthopaedic Research :... Oct 2021The objective of this study is to evaluate, through a systematic review of the scientific literature and meta-analysis, the applications of three-dimensional (3D)... (Meta-Analysis)
Meta-Analysis
The objective of this study is to evaluate, through a systematic review of the scientific literature and meta-analysis, the applications of three-dimensional (3D) printing in the surgical treatment of complex fractures of the appendicular skeleton, mainly in terms of effectiveness and safety. A systematic review of the scientific literature was conducted in MEDLINE (PubMed) and the Cochrane Library combining different keywords. A specific methodological assessment scale was developed and applied to included papers. Ten studies were included; all of them were controlled trials, except for one retrospective observational cohort study. We observed statistically significant differences between the group that used 3D printing and the control group in terms of reduction in surgical time, reduction in the volume of blood lost during surgery and reduction in the number of intraoperative fluoroscopies, in favor of the 3D printing group. No statistically significant differences were observed in terms of fracture healing time, postoperative joint function, or postoperative complications. Meta-analysis revealed more favorable results for 3D-printing compared with conventional surgery, with the greatest difference observed for the number of intraoperative fluoroscopies. 3D printing might be considered effective and safe in the surgical treatment of anatomically complex appendicular skeleton fractures, in terms of reducing surgical time, lost blood volume, and radiation exposure of surgeons and patients.
Topics: Fracture Fixation, Internal; Fractures, Bone; Humans; Observational Studies as Topic; Printing, Three-Dimensional; Retrospective Studies; Skeleton
PubMed: 33280162
DOI: 10.1002/jor.24939 -
Cancers Feb 2022Background: Population-based studies of patients with bone metastases in the appendicular skeleton (aBM) requiring surgery for complete or impending fracture are rare....
Background: Population-based studies of patients with bone metastases in the appendicular skeleton (aBM) requiring surgery for complete or impending fracture are rare. In this epidemiologically-based observational study we created a large population-based cohort of patients treated for aBM, aiming to: (1) monitor possible time-related changes of the incidence of surgical treatment of aBM-lesions, (2) examine differences in the population and care of patients treated at different treatment centers and (3) examine if findings from a previous pilot study regarding absence of a suitable biopsy of the lesions representing debut of cancer or a relapse has improved the awareness of aBM and hereby increased the focus on regular tumor biopsies and follow-up imaging of cancer patients. Methods: We examined a population-based cohort consisting of all patients treated for aBM 2014−2019. Procedures were performed at five secondary surgical centers (SSC) or one tertiary referral Musculoskeletal Tumor Center (MTC). Patients were followed until end of study (30 September 2021) or death. No patients were lost to follow-up. Results: Four-hundred-fifty-seven patients (493 primary aBM-lesions, 482 procedures) were included. Annual incidence of aBM-surgery was 46 aBM-lesions/million. MTC-patients had a significant better preoperative status than SSC-patients considering factors known for survival. Patients with complete fracture experienced longer surgical delay when treated at MTC compared to SSC: 4 (1−9) and 1 (1−3) days (p < 0.001), respectively. Overall survival for the entire cohort was 37% and 11% at 1 and 5 years (MTC and SSC 1 and 5 year respectively: 44% and 15% vs. 29% and 5%, p < 0.001). In patients with debut or relapse of cancer, 8% and 9% had insufficient biopsies, and 21% and 12% had no biopsy, respectively. Comparison showed no change over time. Conclusions: The current study highlights the low awareness on treating aBM at SSC and emphasizes the importance of caution in interpretation of studies not representing an entire population, thus introducing selection bias.
PubMed: 35267566
DOI: 10.3390/cancers14051258 -
Journal of Anatomy May 2022The evolutionary history of archosaurs and their closest relatives is characterized by a wide diversity of locomotor modes, which has even been suggested as a pivotal...
The evolutionary history of archosaurs and their closest relatives is characterized by a wide diversity of locomotor modes, which has even been suggested as a pivotal aspect underlying the evolutionary success of dinosaurs vs. pseudosuchians across the Triassic-Jurassic transition. This locomotor diversity (e.g., more sprawling/erect; crouched/upright; quadrupedal/bipedal) led to several morphofunctional specializations of archosauriform limb bones that have been studied qualitatively as well as quantitatively through various linear morphometric studies. However, differences in locomotor habits have never been studied across the Triassic-Jurassic transition using 3D geometric morphometrics, which can relate how morphological features vary according to biological factors such as locomotor habit and body mass. Herein, we investigate morphological variation across a dataset of 72 femora from 36 different species of archosauriforms. First, we identify femoral head rotation, distal slope of the fourth trochanter, femoral curvature, and the angle between the lateral condyle and crista tibiofibularis as the main features varying between bipedal and quadrupedal taxa, all of these traits having a stronger locomotor signal than the lesser trochanter's proximal extent. We show a significant association between locomotor mode and phylogeny, but with the locomotor signal being stronger than the phylogenetic signal. This enables us to predict locomotor modes of some of the more ambiguous early archosauriforms without relying on the relationships between hindlimb and forelimb linear bone dimensions as in prior studies. Second, we highlight that the most important morphological variation is linked to the increase of body size, which impacts the width of the epiphyses and the roundness and proximodistal position of the fourth trochanter. Furthermore, we show that bipedal and quadrupedal archosauriforms have different allometric trajectories along the morphological variation in relation to body size. Finally, we demonstrate a covariation between locomotor mode and body size, with variations in femoral bowing (anteroposterior curvature) being more distinct among robust femora than gracile ones. We also identify a decoupling in fourth trochanter variation between locomotor mode (symmetrical to semi-pendant) and body size (sharp to rounded). Our results indicate a similar level of morphological disparity linked to a clear convergence in femoral robusticity between the two clades of archosauriforms (Pseudosuchia and Avemetatarsalia), emphasizing the importance of accounting for body size when studying their evolutionary history, as well as when studying the functional morphology of appendicular features. Determining how early archosauriform skeletal features were impacted by locomotor habits and body size also enables us to discuss the potential homoplasy of some phylogenetic characters used previously in cladistic analyses as well as when bipedalism evolved in the avemetatarsalian lineage. This study illuminates how the evolution of femoral morphology in early archosauriforms was functionally constrained by locomotor habit and body size, which should aid ongoing discussions about the early evolution of dinosaurs and the nature of their evolutionary "success" over pseudosuchians.
Topics: Animals; Biological Evolution; Dinosaurs; Femur; Habits; Locomotion; Lower Extremity; Phylogeny
PubMed: 34841511
DOI: 10.1111/joa.13598 -
BMC Musculoskeletal Disorders May 2022Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. In contrast, focal hematopoietic islands within the axial skeleton are a rare entity...
BACKGROUND
Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. In contrast, focal hematopoietic islands within the axial skeleton are a rare entity and can confuse with osteoblastic metastases. This study aimed to characterize typical MRI and CT findings of hematopoietic islands in distinction from osteoblastic metastases to help both radiologists and clinicians, on the one hand, not to overdiagnose this entity and, on the other hand, to decide on a reasonable work-up.
METHODS
We retrospectively analyzed the imaging findings of 14 hematopoietic islands of the axial skeleton in ten patients (nine females, median age = 65.5 years [range, 49-74]) who received both MRI and CT at initial diagnosis between 2006 and 2020. CT-guided biopsy was performed in five cases to confirm the diagnosis, while the other five patients received long-term MRI follow-up (median follow-up = 28 months [range, 6-96 months]). Diffusion-weighted imaging was available in three, chemical shift imaging respectively F- fluorodeoxyglucose PET/CT in two, and Technetium 99 m skeletal scintigraphy in one of the patients.
RESULTS
All lesions were small (mean size = 1.72 cm) and showed moderate hypointense signals on T1- and T2-weighted MRI sequences. They appeared isointense to slightly hyperintense on STIR images and slightly enhanced after gadolinium administration. To differentiate this entity from osteoblastic metastases, CT provides important additional information, as hematopoietic islands do not show sclerosis.
CONCLUSIONS
Hematopoietic islands within the axial skeleton can occur and mimic osteoblastic metastases. However, the combination of MRI and CT allows for making the correct diagnosis in most cases.
Topics: Aged; Bone Neoplasms; Bone and Bones; Female; Fluorodeoxyglucose F18; Gadolinium; Humans; Magnetic Resonance Imaging; Middle Aged; Positron Emission Tomography Computed Tomography; Retrospective Studies
PubMed: 35550061
DOI: 10.1186/s12891-022-05402-w -
Acta Ortopedica Mexicana 2021A metastasis is the tumor cell capacity to migrate from the primary tumor and implant itself in tissues of an organ at a distance by hematogenous, lymphatic or... (Observational Study)
Observational Study
INTRODUCTION
A metastasis is the tumor cell capacity to migrate from the primary tumor and implant itself in tissues of an organ at a distance by hematogenous, lymphatic or contiguity. The main causes of bone metastases are: breast, prostate and lung cancer. It usually occurs in patients over 50 years of age. There is a predilection for metastasizing to the axial skeleton.
OBJECTIVE
To determine the frequency of tumors that produce bone metastases in our institution.
MATERIAL AND METHODS
Observational, cross-sectional, descriptive study, for retrospective analysis of the cases of patients diagnosed with bone metastases.
RESULTS
193 cases; 121 women and 72 men with an age range of 42 to 84 years. Cancers associated with bone metastases were breast, lung, prostate, cervical and renal cancers; to a lesser extent other such as colon, thyroid, liver and skin. The most affected bones were axial skeleton: lumbar and dorsal spine, and in appendicular skeleton the femur in the diaphysiary region and in the humerus the proximal third. At present it has not been possible to improve the effectiveness of timely detection strategies, so bone pain should begin with a protocol of tumor suspicion.
CONCLUSIONS
More than 80% of the patients came for fracture. All patients had a history of pain greater than 12 months with no prior study protocol.
Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Cross-Sectional Studies; Female; Femur; Humans; Humerus; Male; Middle Aged; Retrospective Studies
PubMed: 34731924
DOI: No ID Found -
Annals of the Rheumatic Diseases Dec 2007Entheses are sites where tendons, ligaments, joint capsules or fascia attach to bone. Inflammation of the entheses (enthesitis) is a well-known hallmark of... (Review)
Review
Entheses are sites where tendons, ligaments, joint capsules or fascia attach to bone. Inflammation of the entheses (enthesitis) is a well-known hallmark of spondyloarthritis (SpA). As entheses are associated with adjacent, functionally related structures, the concepts of an enthesis organ and functional entheses have been proposed. This is important in interpreting imaging findings in entheseal-related diseases. Conventional radiographs and CT are able to depict the chronic changes associated with enthesitis but are of very limited use in early disease. In contrast, MRI is sensitive for detecting early signs of enthesitis and can evaluate both soft-tissue changes and intraosseous abnormalities of active enthesitis. It is therefore useful for the early diagnosis of enthesitis-related arthropathies and monitoring therapy. Current knowledge and typical MRI features of the most commonly involved entheses of the appendicular skeleton in patients with SpA are reviewed. The MRI appearances of inflammatory and degenerative enthesopathy are described. New options for imaging enthesitis, including whole-body MRI and high-resolution microscopy MRI, are briefly discussed.
Topics: Humans; Image Processing, Computer-Assisted; Joints; Lower Extremity; Magnetic Resonance Imaging; Rheumatic Diseases; Spondylarthritis; Upper Extremity
PubMed: 17526551
DOI: 10.1136/ard.2007.070243 -
Journal of Clinical Medicine Nov 2023: The aim of this study is to determine MRI features that may be prognostic indicators of local recurrence (LR) in patients treated with curettage and cementation of...
Magnetic Resonance Imaging Features and Prognostic Indicators of Local Recurrence after Curettage and Cementation of Atypical Cartilaginous Tumour in the Appendicular Skeleton.
: The aim of this study is to determine MRI features that may be prognostic indicators of local recurrence (LR) in patients treated with curettage and cementation of atypical cartilaginous tumours (ACTs) in the appendicular skeleton. : This study is a retrospective review of adult patients with histologically confirmed appendicular ACT. The data collected included age, sex, skeletal location and histology from curettage, the presence of LR and oncological outcomes. The pre-operative MRI characteristics of the ACT reviewed by a specialist MSK radiologist included lesion location, lesion length, degree of medullary filling, bone expansion, cortical status and the presence of soft tissue extension. : A total of 43 patients were included, including 9 males and 34 females with a mean age of 42.8 years (range: 25-76 years). Tumours were located in the femur (n = 19), humerus (n = 15), tibia (n = 5), fibula (n = 2) and radius and ulna (n = 1 each). A total of 19 lesions were located in the diaphysis, 12 in the metadiaphysis, 6 in the metaphysis and 6 in the epiphysis. The mean tumour length was 61.0 mm (range: 12-134 mm). The mean follow up was 97.7 months (range: 20-157 months), during which 10 (23.3%) patients developed LR, 7 (70%) of which were asymptomatic and 3 (30%) of which presented with pain. Four patients required repeat surgery with no associated death or evidence of metastatic disease. LR was significantly commoner with tumours arising in the epiphysis or metadiaphysis, but no MRI features were predictive of LR. : No relationship was found between the apparent 'aggressiveness' of an ACT of the appendicular skeleton on MRI and the development of LR following treatment with curettage and cementation.
PubMed: 37959370
DOI: 10.3390/jcm12216905