RESUMEN
The mouse femur, particularly the distal femur, is commonly utilized in orthopedic research. Despite its significance, little is known about the key events involved in the postnatal development of the distal femur. Therefore, investigating the development process of the mouse distal femur is of great importance. In this study, distal femurs of CD-1 mice aged 1, 2, 4, 6, and 8 weeks were examined. We found that the width and height of the distal femur continued to increase till the 4th week, followed with stabilization. Notably, the width to height ratio remained relatively consistent with age. Micro computed tomography analysis demonstrated gradual increases in bone volume/tissue volume, trabecular number, and trabecular thickness from 1 to 6 weeks, alongside a gradual decrease in trabecular separation. Histological analysis further indicated the appearance of the secondary ossification center at approximately 2 weeks, with ossification mostly completed by 4 weeks, leading to the formation of a prototype epiphyseal plate. Subsequently, the epiphyseal plate gradually narrowed at 6 and 8 weeks. Moreover, the thickness and maturity of the bone cortex surrounding the epiphyseal plate increased over time, reaching peak cortical bone density at 8 weeks. In conclusion, to enhance model stability and operational ease, we recommend constructing conventional mouse models of the distal femur between 4 and 8 weeks old.
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Fémur , Animales , Fémur/metabolismo , Fémur/diagnóstico por imagen , Fémur/crecimiento & desarrollo , Ratones , Microtomografía por Rayos X , Placa de Crecimiento/metabolismo , Placa de Crecimiento/crecimiento & desarrollo , Placa de Crecimiento/diagnóstico por imagen , Densidad Ósea , Desarrollo Óseo , Osteogénesis , MasculinoRESUMEN
Premature physeal arrest can cause progressive deformities and functional disabilities of the lower limbs. This study addressed the outcomes after physeal bar resection with or without guided growth (temporary hemiepiphysiodesis) for the treatment of angular limb deformities. We retrospectively analyzed 27 patients (mean 9 years; range, 3-12 years) who underwent physeal bar resection of the distal femur (15 patients), proximal tibia (3 patients), and distal tibia (9 patients) between 2002 and 2020. Fifteen patients underwent physeal bar resection only (Group A), and the other twelve underwent simultaneous guided growth (Group B). The correction angle (angle change between the preoperative and last follow-up values) was compared and analyzed. The overall mean correction angle was 2.9° (range, - 9 to 18.3°). A total of 12 (45%) patients had a > 5° angular deformity improvement (mean, 9.6°; range, 5-18.3°), 9 (33%) had a < 5° angular change; and 6 (22%) had a > 5° worsening of the angular deformity (mean, 6.7°; range, 5.2-9°). The correction angle in Group B (mean 7.6° ± 6.2) was significantly higher than that in Group A (mean - 0.77° ± 6.3) (P = 0.01). We found six (40%) and zero patients with a > 5° angular deformity increase in Groups A and B, respectively (P < 0.047). The group that underwent physeal bar resection with guided growth showed significantly higher correction angles than the group that underwent physeal bar resection alone. Additionally, none of the patients in the guided growth group experienced an increased angular deformity. Therefore, combining guided growth with physeal bar resection may lead to better outcomes in the treatment of growth arrest with angular deformities.
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Fémur , Tibia , Humanos , Niño , Masculino , Femenino , Preescolar , Estudios Retrospectivos , Fémur/cirugía , Fémur/anomalías , Fémur/crecimiento & desarrollo , Tibia/cirugía , Tibia/anomalías , Tibia/crecimiento & desarrollo , Resultado del Tratamiento , Placa de Crecimiento/cirugíaRESUMEN
OBJECTIVES: This study tests if femoral and humeral cross-sectional geometry (CSG) and cross-sectional properties (CSPs) in an ontogenetic series of wild-caught chimpanzees (Pan troglodytes ssp.) reflect locomotor behavior during development. The goal is to clarify the relationship between limb bone structure and locomotor behavior during ontogeny in Pan. MATERIALS AND METHODS: The latex cast method was used to reconstruct cross sections at the midshaft femur and mid-distal humerus. Second moments of area (SMAs) (Ix, Iy, Imax, Imin), which are proportional to bending rigidity about a specified axis, and the polar SMA (J), which is proportional to average bending rigidity, were calculated at section locations. Cross-sectional shape (CSS) was assessed from Ix/Iy and Imax/Imin ratios. Juvenile and adult subsamples were compared. RESULTS: Juveniles and adults have significantly greater femoral J compared to humeral J. Mean interlimb proportions of J are not significantly different between the groups. There is an overall decreasing trend in diaphyseal circularity between the juvenile phase of development and adulthood, although significant differences are only found in the humerus. DISCUSSION: Juvenile chimpanzee locomotion includes forelimb- and hindlimb-biased behaviors. Juveniles and adults preferentially load their hindlimbs relative to their forelimbs. This may indicate similar locomotor behavior, although other explanations including a diversity of hindlimb-biased locomotor behaviors in juveniles cannot be ruled out. Different ontogenetic trends in forelimb and hindlimb CSS are consistent with limb bone CSG reflecting functional adaptation, albeit the complex nature of bone functional adaptation requires cautious interpretations of skeletal functional morphology from biomechanical analyses.
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Diáfisis , Fémur , Húmero , Pan troglodytes , Animales , Pan troglodytes/crecimiento & desarrollo , Pan troglodytes/anatomía & histología , Húmero/anatomía & histología , Húmero/crecimiento & desarrollo , Húmero/fisiología , Diáfisis/anatomía & histología , Diáfisis/crecimiento & desarrollo , Diáfisis/fisiología , Fémur/anatomía & histología , Fémur/crecimiento & desarrollo , Fémur/fisiología , Femenino , Masculino , Locomoción/fisiologíaRESUMEN
As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria-targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)2 , are assembled onto the sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate the synergistic liberation of Zn2+ and Sr2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto-activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr-SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia-induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin-related protein 1 (Drp1) gene down-regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn2+ and Sr2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.
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Diabetes Mellitus/terapia , Hiperglucemia/terapia , Oseointegración/efectos de los fármacos , Prótesis e Implantes , Animales , Benzofenonas/química , Benzofenonas/farmacología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Modelos Animales de Enfermedad , Fémur/efectos de los fármacos , Fémur/crecimiento & desarrollo , Fémur/patología , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Dinámicas Mitocondriales/efectos de los fármacos , Nutrientes/química , Nutrientes/farmacología , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Polietilenglicoles/química , Polietilenglicoles/farmacología , Polímeros/química , Polímeros/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Propiedades de Superficie/efectos de los fármacos , Tibia/efectos de los fármacos , Tibia/crecimiento & desarrollo , Óxido de Zinc/química , Óxido de Zinc/farmacologíaRESUMEN
In ultra-rare bone diseases, information on growth during childhood is sparse. Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin (OPG). OPG inhibits osteoclast activation via the receptor activator of nuclear factor-κB (RANK) pathway. In JPD, overactive osteoclasts result in inflammatory-like bone disease due to grossly elevated bone resorption. Knowledge on the natural history of JPD, including final height and growth, is limited. Most affected children receive long-term antiresorptive treatment, mostly with bisphosphonates, to contain bone resorption, which may affect growth. In this study, we report the follow-up of height, growth velocity, and skeletal maturation in a 16-year-old female patient with JPD. The patient was treated with cyclic doses of pamidronate starting at 2.5 years of age and with 2 doses of denosumab at the age of 8 years, when pamidronate was paused. In the following years, a sustainable decline in a height z-score and a stunted pubertal growth spurt; despite appropriate maturation of the epiphyseal plates of the left hand, the proximal right humerus and both femora were observed. Whether this reflects the growth pattern in JPD or might be associated to the antiresorptive treatments is unclear, since there is very limited information available on the effect of bisphosphonates and denosumab on growth and the growth plate in pediatric patients. Studies are needed to understand the natural history of an ultra-rare bone disease and to assess the effects of antiresorptive treatment on the growing skeleton.
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Denosumab/administración & dosificación , Fémur , Placa de Crecimiento , Húmero , Osteítis Deformante , Pamidronato/administración & dosificación , Adolescente , Niño , Preescolar , Femenino , Fémur/crecimiento & desarrollo , Fémur/metabolismo , Fémur/fisiopatología , Placa de Crecimiento/crecimiento & desarrollo , Placa de Crecimiento/metabolismo , Placa de Crecimiento/fisiopatología , Humanos , Húmero/crecimiento & desarrollo , Húmero/fisiopatología , Osteítis Deformante/tratamiento farmacológico , Osteítis Deformante/metabolismo , Osteítis Deformante/fisiopatología , Osteoprotegerina/metabolismoRESUMEN
BACKGROUND: Several methods are available to estimate leg lengths at maturity to facilitate the determination of timing of epiphysiodesis. We compared the Paley multiplier, Sanders multiplier, and White-Menelaus methods in an epiphysiodesis-aged cohort. We assessed intra- and interrater reliability for Sanders skeletal stages and Greulich and Pyle atlas skeletal age. METHODS: Actual growth was recorded in healthy, unoperated femoral and tibial segments from an epiphysiodesis database. The predicted and actual lengths were compared with use of the Paley multiplier and White-Menelaus methods, Greulich and Pyle skeletal age, and the Sanders multiplier using Sanders stages. Intra- and interrater reliability were assessed in a separate group of 76 skeletal age films. RESULTS: The cohort included 148 femora and 195 tibiae in 197 patients. Femoral length at maturity was slightly underestimated by the Sanders multiplier and staging, was overestimated by the Paley multiplier and skeletal age, and was most accurately predicted with use of the White-Menelaus formula and skeletal age. All methods overestimated tibial length at maturity. The whole-leg prediction accuracy of the Sanders multiplier and White-Menelaus formula were comparable and were more accurate than that of the Paley multiplier. For Sanders skeletal staging, the interrater reliability varied from 0.86 to 0.88 and the intrarater reliability varied from 0.87 to 0.96. For Greulich and Pyle skeletal age, the interrater reliability varied from 0.87 to 0.89 and the intrarater reliability varied from 0.91 to 0.95. CONCLUSIONS: Use of the Sanders multiplier and skeletal stages was more accurate than the Paley multiplier and skeletal age in this cohort. Use of the White-Menelaus formula and skeletal age was slightly more accurate in predicting femoral length and slightly less accurate in predicting tibial length compared with the Sanders multiplier. Intra- and interrater reliability were similar between Sanders skeletal stages and Greulich and Pyle atlas skeletal age. The White-Menelaus formula and skeletal age was the recommended method for predicting lower-extremity segment lengths at maturity and epiphysiodesis effect. Although easier to recall without referencing an atlas and not sex-specific, Sanders skeletal staging does not correspond directly to years of growth remaining, and thus cannot be used with the White-Menelaus formula. CLINICAL RELEVANCE: The Greulich and Pyle atlas to determine skeletal age and the White-Menelaus formula to determine growth remaining are reliable predictors of epiphysiodesis effect in the lower extremities.
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Fémur/crecimiento & desarrollo , Fémur/cirugía , Diferencia de Longitud de las Piernas/diagnóstico , Diferencia de Longitud de las Piernas/cirugía , Adolescente , Determinación de la Edad por el Esqueleto , Niño , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. METHODS: In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. RESULTS: An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. CONCLUSIONS: Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.
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Compuestos de Bencidrilo/orina , Disruptores Endocrinos/orina , Fenoles/orina , Sulfonas/orina , Adulto , Peso al Nacer , Femenino , Fémur/anatomía & histología , Fémur/crecimiento & desarrollo , Desarrollo Fetal , Cabeza/anatomía & histología , Cabeza/crecimiento & desarrollo , Humanos , Recién Nacido , Masculino , Embarazo , Estudios ProspectivosRESUMEN
Testosterone and alendronate have been identified as two bone healing compounds which, when combined, synergistically stimulate bone regeneration. This study describes the development of a novel ultrasonic spray coating for sustained release of ancillary amounts of testosterone and alendronate encapsulated in PLGA 5004A as a carrier. Due to the low amounts of testosterone and alendronate used, sensitive in vitro assays were developed to determine in vitro release. The ultrasonic spray coating technology was optimized for coating titanium screws and pericardial collagen membranes, with the aim to improve osseo-integration and (guided) bone regeneration, respectively, without interfering with their primary mode of action. In vitro release analysis of collagen membranes and screws showed up to 21 days sustained release of the compounds without a burst release. Subsequent preclinical studies in rat and rabbit models indicated that testosterone and alendronate coated membranes and screws significantly improved bone regeneration in vivo. Coated membranes significantly improved the formation of new bone in a critical size calvarial defect model in rats (by 160% compared to controls). Coated screws implanted in rabbit femoral condyles significantly improved bone implant contact (69% vs 54% in controls), bone mineral density (121%) and bone volume (119%) up to 1.3 mm from the implant. Based on the results obtained, we suggest that implants or membranes enabled with local sustained delivery of ancillary amounts of testosterone and alendronate can be a promising system to stimulate local bone regeneration resulting in improved osseo-integration of implants and improved healing of bone defects and fractures.
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Alendronato/farmacología , Regeneración Ósea/efectos de los fármacos , Oseointegración/efectos de los fármacos , Testosterona/farmacología , Animales , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacología , Regeneración Ósea/fisiología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Preparaciones de Acción Retardada/farmacología , Modelos Animales de Enfermedad , Fémur/crecimiento & desarrollo , Fémur/cirugía , Humanos , Masculino , Oseointegración/fisiología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Prótesis e Implantes , Conejos , Ratas , Titanio/química , Titanio/uso terapéuticoRESUMEN
In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding 'queen' status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also upregulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength.
Some social animals are highly cooperative creatures that live in tight-knit colonies. Bees and ants are perhaps the most well-known examples of social insects, while Damaraland mole-rats and naked mole-rats, two rodent species found in southern and eastern Africa, are among the most cooperative mammal species. In these colony-forming animals, only one or a few females reproduce and these fertile females are frequently referred to as "queens". When an animal becomes a queen, her body shape can change dramatically to support the demands of high fertility and frequent reproduction. The molecular basis of such changes has been well-described in social insects. However, they are poorly understood in mammals. To address this knowledge gap, Johnston et al. studied how transitioning to queen status affects bone growth and structural integrity in Damaraland mole-rats, as well as body shape and size. The experiments compared non-breeding female mole-rats with other adult females recently paired with a male to become the sole breeder of a new colony. Johnston et al. also used bone-derived cells grown in the laboratory to assess underlying gene regulatory changes in new queen mole-rats. Johnston et al. showed that transitioning to the role of queen leads to a cascade of skeletal changes accompanied by shifts in the regulation of genetic pathways linked to bone growth. Queen mole-rats show accelerated growth in the spinal column of their lower back. These bones are called lumbar vertebrae and this likely allows them to have larger litters. However, queen mole-rats also lose bone growth potential in their leg bones and develop thinner thigh bones, which may increase the risk of bone fracture. Therefore, unlike highly social insects, mole-rats do not seem to have escaped the physical costs of intensive reproduction. This work adds to our understanding of the genes and physical traits that have evolved to support cooperative behaviour in social animals, including differences between insects and mammals. It also shows, with a striking example, how an animal's genome responds to social cues to produce a diverse range of traits that reflect their designated social role.
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Evolución Biológica , Desarrollo Óseo , Fémur/crecimiento & desarrollo , Fertilidad , Genoma , Vértebras Lumbares/crecimiento & desarrollo , Ratas Topo/crecimiento & desarrollo , Conducta Sexual Animal , Factores de Edad , Animales , Desarrollo Óseo/genética , Conducta Cooperativa , Fertilidad/genética , Regulación de la Expresión Génica , Ratas Topo/genética , Ratas Topo/psicología , Factores Sexuales , Conducta SocialRESUMEN
Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) or inactivating mutations in guanylyl cyclase-B (GC-B), also known as NPR-B or Npr2, cause short-limbed dwarfism. FGFR3 activation causes dephosphorylation and inactivation of GC-B, but the contribution of GC-B dephosphorylation to achondroplasia (ACH) is unknown. GC-B7E/7E mice that express a glutamate-substituted version of GC-B that cannot be inactivated by dephosphorylation were bred with mice expressing FGFR3-G380R, the most common human ACH mutation, to determine if GC-B dephosphorylation is required for ACH. Crossing GC-B7E/7E mice with FGFR3G380R/G380R mice increased naso-anal and long (tibia and femur), but not cranial, bone length twice as much as crossing GC-B7E/7E mice with FGFR3WT/WT mice from 4 to 16 weeks of age. Consistent with increased GC-B activity rescuing ACH, long bones from the GC-B7E/7E/FGFR3G380R/G380R mice were not shorter than those from GC-BWT/WT/FGFR3WT/WT mice. At 2 weeks of age, male but not female FGFR3G380R/G380R mice had shorter long bones and smaller growth plate hypertrophic zones, whereas female but not male GC-B7E/7E mice had longer bones and larger hypertrophic zones. In 2-week-old males, crossing FGFR3G380R/G380R mice with GC-B7E/7E mice increased long bone length and hypertrophic zone area to levels observed in mice expressing WT versions of both receptors. We conclude that preventing GC-B dephosphorylation rescues reduced axial and appendicular skeleton growth in a mouse model of achondroplasia.
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Acondroplasia/genética , Desarrollo Óseo/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptores del Factor Natriurético Atrial/genética , Animales , Tamaño Corporal/genética , Fémur/crecimiento & desarrollo , Placa de Crecimiento/crecimiento & desarrollo , Placa de Crecimiento/patología , Ratones , Ratones Transgénicos , Tamaño de los Órganos , Fosforilación , Receptores del Factor Natriurético Atrial/metabolismo , Cráneo/crecimiento & desarrollo , Tibia/crecimiento & desarrolloRESUMEN
BACKGROUND: The ability to estimate skeletal maturity using a knee radiograph would be useful in anterior cruciate ligament (ACL) injuries and limb-length discrepancy in immature patients. Currently, a quick, accurate, and reproducible method is lacking. METHODS: Serial knee radiographs made 3 years before to 2 years following the chronologic age associated with 90% of final height (an enhanced skeletal maturity gold standard compared with peak height velocity) were analyzed in 78 children. The Pyle and Hoerr (PH) knee method was simplified by developing discrete stages for the distal part of the femur, the proximal part of the tibia, the proximal part of the fibula, and the patella. The Roche-Wainer-Thissen (RWT) knee method was simplified from the 36 original parameters to 14 parameters by removing parameters that were poorly defined, were not relevant to the peripubertal age range, were poorly correlated with 90% final height, or were poorly reliable on a 20-radiograph pilot analysis. We also compared the recently described central peak value (CPV) of the distal part of the femur. The Greulich and Pyle (GP) left-hand bone age was included for comparison. RESULTS: In this study, 326 left knee radiographs from 41 girls (age range, 7 to 15 years) and 37 boys (age range, 9 to 17 years) were included. Stepwise linear regression showed higher correlation in predicting years from 90% final height using the modified RWT and demographic characteristics (R2 = 0.921) compared with demographic characteristics alone (R2 = 0.840), CPV and demographic characteristics (R2 = 0.866), GP and demographic characteristics (R2 = 0.899), and PH and demographic characteristics (R2 = 0.902). Seven parameters were excluded from the RWT and demographic characteristics model using stepwise linear regression and generalized estimating equations analysis, leaving 7 parameters (2 femoral, 4 tibial, and 1 fibular) in the final model. Compared with RWT and demographic characteristics (R2 = 0.921), there were minimal incremental increases by adding CPV (R2 = 0.921), GP (R2 = 0.925), or PH (R2 = 0.931). CONCLUSIONS: This large analysis of knee skeletal maturity systems isolated 7 discrete radiographic knee parameters that theoretically outperform the GP bone age in estimating skeletal maturity. CLINICAL RELEVANCE: We present a modified knee skeletal maturity system that can potentially preclude the need for additional imaging of the hand and wrist in reliably estimating skeletal maturity.
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Determinación de la Edad por el Esqueleto/métodos , Artrografía/métodos , Rodilla/diagnóstico por imagen , Adolescente , Factores de Edad , Artrografía/estadística & datos numéricos , Estatura , Niño , Femenino , Fémur/diagnóstico por imagen , Fémur/crecimiento & desarrollo , Peroné/diagnóstico por imagen , Peroné/crecimiento & desarrollo , Humanos , Rodilla/crecimiento & desarrollo , Modelos Lineales , Masculino , Rótula/diagnóstico por imagen , Rótula/crecimiento & desarrollo , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Tibia/crecimiento & desarrolloRESUMEN
Cadmium (Cd) is toxic to the skeletal system resulting in bone loss and pain. We aimed at determining the effect of chronic Cd exposure on bone density and microarchitecture along with changes in the density of a subset of sensory and sympathetic nerve fibers innervating the developing rat femur. Newborn male Wistar rats were injected daily for 49 days with CdCl2 (1 mg/kg i.p.) or saline solution (control group). At the day of sacrifice, levels of Cd in the right femur, liver and kidney were determined by atomic absorption spectrophotometry. Additionally, microCT followed by immunohistochemical analyses were performed in the left femur. Results showed Cd accumulation in trabecular bone neared levels seen in liver and kidney. Cd concentration in cortical bone was significantly lower versus trabecular bone. MicroCT analysis revealed that Cd-exposed rats had a significant decrease in trabecular bone parameters at the distal femoral metaphysis; however, most of the cortical bone parameters were not significantly affected. Cd-exposed rats showed a significant loss of TH+ sympathetic nerve fibers, but not of CGRP+ sensory nerve fibers, at the level of bone marrow of the femoral diaphysis as compared to control rats. This study shows that Cd negatively affects bone density and microarchitecture of trabecular bone and decreases the density of sympathetic nerve fibers innervating rat femur. Future studies are warranted to determine the toxigenic mechanisms of Cd on sympathetic nerves and how sympathetic denervation influences bone loss in animals exposed to Cd.
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Densidad Ósea/efectos de los fármacos , Cadmio/toxicidad , Hueso Esponjoso/efectos de los fármacos , Fémur/efectos de los fármacos , Fibras Nerviosas/efectos de los fármacos , Animales , Cadmio/administración & dosificación , Femenino , Fémur/crecimiento & desarrollo , Inyecciones Intraperitoneales , Embarazo , Ratas , Ratas WistarRESUMEN
ABSTRACT: Age estimation in forensic medicine practice is of particular importance to the legal systems, and it is one of the current research topics in forensic medicine. Age determination is most frequently performed by radiological methods, but recently, nonionized methods are preferred for nonmedical indications. Therefore, we aimed to examine feasibility of MRI imaging, which provides nonionized, noninvasive, and detailed images, in forensic age estimation and to expand the database on this subject. The MRI images of the patients between the ages of 10 and 25 years, who visited Cukurova University Faculty of Medicine between January 2012 and April 2018 for any reason, were retrospectively analyzed according to the staging method described by Dedouit et al. The stage 5 ossification in distal femoral epiphysis indicated an age over 18 years in both sexes (except for 2 cases of 14 and 15 years). The stage 5 ossification in proximal tibial epiphysis indicated an age older than 18 years (except for 1 male case at the age of 15 years and 2 female cases at the age of 14 and 17 years, respectively). It was determined that stage 1 and stage 2 in both distal femur and proximal tibial epiphysis were last seen in younger than 18 years in both sexes. Our study data show that MRI imaging is a nonionized method that can be used in addition to other radiological methods in determining the age limit of 18 years.
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Determinación de la Edad por el Esqueleto/métodos , Epífisis/diagnóstico por imagen , Fémur/diagnóstico por imagen , Imagen por Resonancia Magnética , Osteogénesis , Tibia/diagnóstico por imagen , Adolescente , Adulto , Niño , Epífisis/crecimiento & desarrollo , Femenino , Fémur/crecimiento & desarrollo , Humanos , Masculino , Estudios Retrospectivos , Tibia/crecimiento & desarrollo , Adulto JovenRESUMEN
The evaluation of epiphyseal areas by magnetic resonance imaging (MRI) for forensic age estimation is an important supportive diagnostic method to prevent repeated radiation exposure without a valid medical reason. There are still not enough individuals being analyzed with MRI for age estimation. The aim of this study was to investigate the utility of T1-weighted turbo spin echo (T1-TSE) MRI sequences in determining the degree of ossification of the distal femoral and proximal tibial epiphyses in a Turkish population. In this study, images from 649 patients (335 males and 314 females) aged 10-30 years were retrospectively evaluated with sagittal T1-weighted turbo spin echo (T1-TSE) MRI sequences of the knee. Proximal tibial and distal femoral epiphysis were scored by two different observers twice using the combined staging system described by Schmeling and Kellinghaus. Spearman's rank correlation analysis indicated a significant positive relationship between age and ossification stages of the distal femoral and proximal tibial epiphyses (p < 0.001). The intra- and inter-observer reliabilities in evaluating the femur and tibia were separately determined and gave promising results and Cohen's kappa statistics ranged from κ = 0.886 and κ = 0.961. The minimal ages of patients with stage 4 ossification were 15.1 years for females and 15.8 years for males for the distal tibial epiphysis and 15.4 years for females and 17 years for males for the distal femoral epiphysis. This study show that (T1-TSE) MRI and the applicability and Schmeling and Kellinghaus staging method of the knee can be performed for living 14- to 17-year-old individuals in need of a supportive noninvasive method for estimating forensic age.
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Determinación de la Edad por el Esqueleto , Epífisis/diagnóstico por imagen , Fémur/diagnóstico por imagen , Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Osteogénesis/fisiología , Tibia/diagnóstico por imagen , Adolescente , Adulto , Niño , Epífisis/crecimiento & desarrollo , Femenino , Fémur/crecimiento & desarrollo , Humanos , Masculino , Tibia/crecimiento & desarrollo , Turquía/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to investigate how much variation in adult stature and body mass can be explained by growth disruption among soldiers who served in Napoleon's Grand Army during the Russian Campaign of 1812. METHODS: Linear enamel hypoplasia (LEH) were recorded as representations of early life growth disruption, while the impact on future growth was assessed using maximum femur length (n = 73) as a proxy for stature and maximum femoral head diameter (n = 25) as a proxy for body mass. LEH frequency, severity, age at first formation, and age at last formation served as explanatory variables in a multiple regression analysis to test the effect of these variables on maximum femur length and maximum femoral head diameter. RESULTS: The multiple regression model produced statistically significant results for maximum femur length (F-statistic = 3.05, df = 5 and 67, P = .02), with some variation in stature (adjusted r2 = 0.13) attributable to variation in growth disruption. The multiple regression model for maximum femoral head diameter was not statistically significant (F-statistic = 1.87, df = 5 and 19, P = .15). CONCLUSIONS: We hypothesized stress events during early life growth and development would have significant, negative, and cumulative effects on growth outcomes in adulthood. The results did not support our hypothesis. Instead, some variables and interactions had negative effects on stature, whereas others had positive effects. This is likely due to catch-up growth, the relationship between acute and chronic stress and growth, resilience, and plasticity in human growth over the life course.
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Estatura , Índice de Masa Corporal , Hipoplasia del Esmalte Dental/patología , Fémur/crecimiento & desarrollo , Crecimiento , Personal Militar/historia , Arqueología , Esmalte Dental/patología , Cabeza Femoral/crecimiento & desarrollo , Francia , Historia del Siglo XIX , Humanos , Lituania , Masculino , Personal Militar/estadística & datos numéricos , Federación de RusiaRESUMEN
The shortcomings of autografts and allografts in bone defect healing have prompted researchers to develop suitable alternatives. Numerous biomaterials have been developed as bone graft substitutes each with their own advantages and disadvantages. However, in order to test if these biomaterials provide an adequate replacement of the clinical standard, a clinically representative animal model is needed to test their efficacy. In this chapter, we describe a mouse model that establishes a critical sized defect in the mid-diaphysis of the femur to evaluate the performance of bone graft substitutes. This is achieved by performing a femoral ostectomy and stabilization utilizing a femoral plate and titanium screws. The resulting defect enables the bone regenerative potential of bone graft substitutes to be investigated. Lastly, we provide instruction on assessing the torsional strength of the healed femurs to quantitatively evaluate the degree of healing as a primary outcome measure.
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Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos , Trasplante Óseo/métodos , Diáfisis/efectos de los fármacos , Fémur/cirugía , Animales , Autoinjertos/trasplante , Tornillos Óseos , Sustitutos de Huesos/farmacología , Diáfisis/crecimiento & desarrollo , Modelos Animales de Enfermedad , Fémur/crecimiento & desarrollo , Fémur/fisiopatología , Curación de Fractura/efectos de los fármacos , Humanos , RatonesRESUMEN
Here we examine the bone histology of the femora and humeri of the Western Grey Kangaroo, Macropus fuliginosus. Our results reveal that bone modelling in response to ontogenetic growth and the development of tuberosities on the femur, and especially in the humerus, lead to a highly complex histology. We propose that the alternating fast and slow rates of bone deposition are seasonal, and are likely correlated with heterothermy related to ecological constraints during the summer months. In females, after the fourth growth mark in the femur, there is a distinctive change to a more lamellar textured bone deposition with sparse vascularisation, directly indicating a slowdown in growth. However, in males, the zones remain woven textured and well vascularised, which is indicative of continued fast growth. Here we also report the novel occurrence of a fibrocartilaginous entheses for the attachment of the m. quadratus femoris to the caudal femoral tuberosity. Using a combination of methodologies, we show that perimeter measurements of growth marks provide a reasonable estimation of the age of kangaroos. Additionally, we observed large individuals that have ceased diaphyseal appositional growth of the femur and the humerus, as well as fusion of the distal epiphyses of both bones, though the proximal epiphyses may remain unfused.
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Desarrollo Óseo , Fémur/crecimiento & desarrollo , Fibrocartílago/crecimiento & desarrollo , Húmero/crecimiento & desarrollo , Macropodidae/crecimiento & desarrollo , Animales , Femenino , Masculino , Estaciones del AñoRESUMEN
Overexpression of the nucleotide-binding leucine-rich repeat protein 3 (NLRP3) inflammasome in chronic auto-immune diseases leads to skeletal anomalies, with severe osteopenia due to the activation of osteoclasts. Reproducing this phenotype in Nlrp3 knock-in mice has provided insights into the role of NLRP3 in bone metabolism. We studied the role of NLRP3 in physiological bone development using a complete Nlrp3 knock-out mouse model. We found impaired skeletal development in Nlrp3-/- mice, resulting in a shorter stature than that of Nlrp3+/+ mice. These growth defects were associated with altered femur bone growth, characterized by a deficient growth plate and an osteopenic profile of the trabeculae. No differences in osteoclast recruitment or activity were observed. Instead, Nlrp3-/- femurs showed a less mineralized matrix in the trabeculae than those of Nlrp3+/+ mice, as well as less bone sialoprotein (BSP) expressing hypertrophic chondrocytes. In vitro, primary osteoblasts lacking NLRP3 expression showed defective mineralization, together with the downregulation of BSP expression. Finally, follow-up by micro-CT highlighted the role of NLPR3 in bone growth, occurring early in living mice, as the osteopenic phenotype diminishes over time. Overall, our data suggest that NLRP3 is involved in bone edification via the regulation of hypertrophic chondrocyte maturation and osteoblast activity. Furthermore, the defect appeared to be transitory, as the skeleton recovered with aging.
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Hueso Esponjoso/crecimiento & desarrollo , Diferenciación Celular , Fémur/crecimiento & desarrollo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Osteoblastos/metabolismo , Osteogénesis , Factores de Edad , Animales , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/metabolismo , Hueso Esponjoso/patología , Células Cultivadas , Condrocitos/metabolismo , Condrocitos/patología , Femenino , Fémur/diagnóstico por imagen , Fémur/metabolismo , Fémur/patología , Genotipo , Inflamasomas/genética , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Osteoblastos/patología , Osteoclastos/metabolismo , Osteoclastos/patología , Osteopontina/metabolismo , Fenotipo , Microtomografía por Rayos XRESUMEN
Introdução - As elevadas taxas de mortalidade neonatal e a prevalência de bebês nascidos pequenos para idade gestacional (PIG) ainda apresentadas por regiões de baixa e média renda indicam a necessidade de investigação sobre fatores que influenciam o crescimento fetal. Medidas biométricas fetais
Introduction Elevated rates of neonatal mortality and small-for-gestational-age (SGA) babies in low- and middle-income regions indicate the need to investigate factors associated with fetal growth. Fetal biometric measurements below the 10th percentile for gestational age (GA) reflect failure in achieving growth potential and provide opportunities for prenatal interventions. Objective To investigate factors associated with fetal biometric measurements below the 10th percentile assessed at early third trimester among pregnant women in the MINA-Brazil study. Methods This was a prospective analysis of pregnant women living in the urban area of Cruzeiro do Sul (AC), followed up since the antenatal period. Screening of participants took place from February 2015 to January 2016. A sociodemographic and health history interview was carried out along with two clinical assessments, scheduled between the second and third trimesters of pregnancy, to collect data on lifestyle factors and complications during pregnancy, anthropometric evaluation, blood collection, and ultrasound scan assessing fetal biometric measurements of head circumference (HC), abdominal circumference (AC) and femoral length (FL). Poisson regression models with hierarchical selection of variables were fitted for factors associated with occurrence of fetal measurements below the 10th percentile at early third trimester. Prevalence ratios (PR) and 95% confidence intervals (95%CI) were estimated. Results Among 426 participants (mean age 25 years (SD 6.4) and gestational age 27.8 weeks (SD 1.7)), 11.3%, 8.9% e 9.4% had fetuses with HC, AC, FL below the 10th percentile at early third trimester. Fetal biometric measurements below the 10th percentile were negatively associated with higher maternal education level, which denoted over 50% of protection (HC: PR 0.47, 95%CI 0.28; 0.81; AC: PR 0.48, 95%CI 0.26; 0.87; and FL: PR 0.48, 95%CI 0.27; 0.86). Adjusted for maternal education level, nulliparity (PR 1.94, 95%CI 1.10; 3.43), higher pre-gestational body mass index (BMI) (PR 1.06, 95%CI 1.01; 1.11), and pre-gestational alcohol consumption (PR 1.80, 95%CI 0.98; 3.30) were associated with HC measurements below the 10th percentile. Maternal height (p for trend 0.039) and pre-gestational alcohol consumption (PR 2.55, 95%CI 1.31; 4.96) were also associated with AC measurements below the 10th percentile. Association between higher average screen time per day during antenatal follow-up and FL measurements below the 10th percentile were observed as well (p for trend 0.031). Higher maternal education level, which may provide better material and non-material conditions, seems to protect fetal growth from failure to reach potential fetal size for GA. Positive associations observed with obstetric and antenatal conditions may be mediated by biological factors or gestational dysfunctions to incur in fetal measurements below the 10th percentile. Conclusion The occurrence of fetal biometric measurements below the 10th percentile for GA and their associated factors corroborate pre-pregnancy and antenatal care improvements anchored in equity policies, and for new strategies prior to birth that optimize the window of opportunity in the first thousand days of life.
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Recién Nacido Pequeño para la Edad Gestacional , Cefalometría , Biometría , Circunferencia Abdominal , Fémur/crecimiento & desarrollo , Retardo del Crecimiento Fetal , FetoRESUMEN
Polychlorinated biphenyls (PCBs) are ubiquitous, persistent, organic pollutants also considered endocrine-disrupting chemicals. Our study examined the effects of lactational exposure to nondioxin-like PCB-155 and/or dioxin-like PCB-169 on longitudinal femur growth at the distal epiphyseal growth plate (EGP) in young rats at three different ages [postnatal days (PNDs) 9, 22, and 42]. After delivery, lactating rats were divided into four groups (PCB-169, PCB-155, PCB-155 + 169, and control) and administered PCBs intraperitoneally. The femurs of offspring were used to estimate growth rate (µm/day), and histomorphometric analysis on the distal femur included the thickness of the EGP and zones of proliferation and hypertrophy with calcification. Stereometry was used to determine trabecular bone volume density. In the PCB-169 and PCB-155 + 169 groups, PCB-169 affected longitudinal bone growth in the early postnatal period by interfering with chondrocytes in the EGP zone of proliferation and, to a lesser extent, the zone of hypertrophy. Morphometric alterations in EGP structure diminished until puberty. A slow growth rate persisted in the PCB-169 group until PND 42, while in the PCB-155 group, a fast growth rate between PNDs 9 to 22 was significantly reduced between PNDs 22 to 42. Sterometric assessment showed decreased trabecular bone volume in the PCB-155 + 169 group compared with that in the control on PND 9 and increased in the PCB-169 group compared with that in the PCB-155 group on PND 42. To summarize, studied PCB congeners exerted congener- and age-dependent effects on femur growth rate and its histomorphometric characteristics.