Cross-sectional and longitudinal analysis of bone age maturation during peri-pubertal growth in children with type I, III and IV osteogenesis imperfecta.

Osteogenesis imperfecta (OI)is a rare genetically heterogeneous disorder caused by changes in the expression or processing of type I collagen. Clinical manifestations include bone fragility, decreased linear growth, and skeletal deformities that vary in severity. In typically growing children, skeletal maturation proceeds in a predictable pattern of changes in the size, shape, and mineralization on the hand and wrist bones that can be followed radiographically known at the bone age. Assessment of bone age can be clinically used to assess time remaining for linear growth, and the onset and duration of puberty, both of which can be useful in determining the timing of some surgeries or the interpretation of other imaging modalities such as bone densitometry. Additionally, deviations in the expected maturation process of the bone age may prompt or assist in the work up of a significant delay or advancement in a child's growth pattern. The primary aim of our study was to determine whether the bone age in children with a skeletal disorder such as OI follow the same pattern and rate of bone maturation compared to a control population. Using participants from the Natural History Study of the Brittle Bone Disorders Consortium, we analyzed 159 left hand and wrist radiographs (bone age) for a cross-sectional analysis and 55 bone ages repeated at approximately 24 months for a longitudinal analysis of skeletal maturation. Bone ages were read by a pediatric endocrinologist and by an automated analysis using a program called BoneXpert. Our results demonstrated that in children with mild-to-moderate OI (types I and IV), the skeletal maturation is comparable to chronological age-mated controls. For those with more severe forms of OI (type III), there is a delayed pattern of skeletal maturation of less than a year (10.5 months CI 5.1-16) P = 0.0012) at baseline and a delayed rate of maturation over the two-year follow up compared to type I (P = 0.06) and type III (P = 0.02). However, despite these parameters being statistically different, they may not be clinically significant. We conclude the bone age, with careful interpretation, can be used in the OI population in a way that is similar to the general pediatric population.

Root resorption of primary molars and dental development of premolars in children with Osteogenesis Imperfecta medicated with bisphosphonates, grouped according to age and gender.

BACKGROUND: Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility and skeletal alterations. The administration of bisphosphonates (BPs) to patients with OI reduces pain, thereby improving their quality of life. The main mechanism of action of BPs is the inhibition of osteoclast action. In the oral cavity of children with OI during growth and development, physiological processes that require the function of osteoclasts occur. The aim of this investigation was to study the dental development of premolars and the root resorption of primary molars in children with OI medicated with BPs according to age and sex. METHODS: An observational and analytical study was designed. The study sample consisted of 26 6- to 12-year-old children with a confirmed diagnosis of OI treated with BPs with available panoramic radiographs. The control group consisted of 395 children with available panoramic radiographs. Both groups were divided into subgroups according to sex and age. The third quadrant was studied, focusing on the first left temporary molar (7.4), the second left temporary molar (7.5), the first left permanent premolar (3.4) and the second left permanent premolar (3.5). The Demirjian method was used to study the dental development of 3.4 and 3.5, and the Haavikko method was used to study the root resorption of 7.4 and 7.5. The Mann‒Whitney U test was used for comparisons, and p < 0.05 indicated statistical significance. RESULTS: The mean chronological age of the 421 patients was 9.21 years (95% CI 9.05-9.37). The sample was reasonably balanced by sex, with 52.5% (221 patients) boys versus 47.5% (200 patients) girls. Delayed exfoliation and tooth development were described in children with OI (p = 0.05). According to sex, the root resorption of primary molars and tooth development were significantly lower in boys in both groups and in girls in the OI group, but the differences between the age groups were not significant. CONCLUSIONS: Children with OI treated with BPs exhibit delayed dental development of the premolars and delayed root resorption of the primary molars. Boys exhibited delays in both variables, but the differences by age subgroup were not significant. These clinical findings support the importance of clinically and radiographically monitoring the dental development and root resorption of primary teeth in children with OI treated with BPs to avoid alterations of the eruptive process.

Low muscle density in children with osteogenesis imperfecta using opportunistic low-dose chest CT: a case-control study.

BACKGROUND: The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. METHODS: This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. RESULTS: 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm2, p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm2, p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively). CONCLUSIONS: Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children.

Pregnancy complicated by severe osteogenesis imperfecta poses a challenge for the anaesthetist: A case report.

Pregnant women with severe osteogenesis imperfecta (OI) are uncommon, and there are limited data regarding anaesthesia for caesarean section in these high-risk individuals. The presence of anatomical and physiological abnormalities can pose technical challenges for the anaesthetist. This report describes the successful implementation of epidural anaesthesia in a parturient with severe OI. To our knowledge, this is the first documented use of ultrasound-assisted neuraxial anaesthesia and wrist blood pressure monitoring in such patients undergoing caesarean section. Understanding the pathophysiological changes associated with OI is crucial for ensuring safe administration of anaesthesia to these women.

Gnathodiaphyseal dysplasia: Diagnostic clues from two fetal cases and literature review.

This article presents two fetal cases of gnathodiaphyseal dysplasia (GDD), a rare autosomal dominant disorder, and reviews the relevant literature. The cases involved two fetuses exhibiting bone bowing, which led to the diagnosis of GDD. Genetic testing revealed two de novo variants of the ANO5 gene, confirming the diagnosis. A literature review was conducted to explore GDD's clinical and paraclinical presentation, diagnosis, and management. GDD is a rare but frequently inherited cause of bone fragility and jaw lesions characterized by a gain-of-function variant within the ANO5 gene. Clinical manifestations range from recurrent dental infections with mild jaw lesions to severe bone fragility with several fractures associated with large jaw lesions requiring disfiguring surgeries. Diagnostic techniques depend on the context and include targeted genetic testing of ANO5, untargeted molecular analysis with whole-exome sequencing, or whole-genome sequencing. This case report highlights the importance of recognizing GDD as a novel cause of bone bowing and fractures during pregnancy. By summarizing the literature, this article contributes to healthcare professionals' knowledge and improves the recognition, diagnosis, and care of patients with GDD.

Bone microarchitecture and strength assessment in adults with osteogenesis imperfecta using HR-pQCT: normative comparison and challenges.

Data on bone microarchitecture in osteogenesis imperfecta (OI) are scarce. The aim of this cross-sectional study was to assess bone microarchitecture and strength in a large cohort of adults with OI using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to evaluate challenges of using HR-pQCT in this cohort. Second-generation HR-pQCT scans were obtained at the distal radius and tibia in 118 men and women with Sillence OI type I, III, or IV using an extremity-length-dependent scan protocol. In total, 102 radius and 105 tibia scans of sufficient quality could be obtained, of which 11 radius scans (11%) and 14 tibia scans (13%) had a deviated axial scan angle as compared with axial angle data of 13 young women. In the scans without a deviated axial angle and compared with normative HR-pQCT data, Z-scores at the radius for trabecular bone mineral density (BMD), number, and separation were -1.6 ± 1.3, -2.5 ± 1.4, and -2.7 (IQR: 2.7), respectively. They were -1.4 ± 1.5 and -1.1 ± 1.2 for stiffness and failure load and between ±1 for trabecular thickness and cortical bone parameters. Z-scores were significantly lower for total and trabecular BMD, stiffness, failure load, and cortical area and thickness at the tibia. Additionally, local microarchitectural inhomogeneities were observed, most pronounced being trabecular void volumes. In the scans with a deviated axial angle, the proportion of Z-scores <-4 or >4 was significantly higher for trabecular BMD and separation (radius) or most total and trabecular bone parameters (tibia). To conclude, especially trabecular bone microarchitecture and bone strength were impaired in adults with OI. HR-pQCT may be used without challenges in most adults with OI, but approximately 12% of the scans may have a deviated axial angle in OI due to bone deformities or scan positioning limitations. Furthermore, standard HR-pQCT parameters may not always be reliable due to microarchitectural inhomogeneities nor fully reflect all inhomogeneities.

OI is a rare condition with large clinical heterogeneity. One of the major characteristics associated with OI is the increased fracture risk due to defects in bone structure and material. Data on the defects in bone structure at the micrometer level (i.e. bone microarchitecture) are scarce. Bone microarchitecture can be assessed noninvasively using HR-pQCT, but its use in OI has not extensively been described. Yet, potential challenges may arise related to among others the occurrence of short extremities and skeletal deformities in OI. We assessed bone microarchitecture and strength in 118 adults with OI types I, III, or IV using HR-pQCT with an extremity-length-dependent scan protocol. Additionally, we evaluated potential challenges of using HR-pQCT in this cohort. Our results demonstrated that predominantly trabecular microarchitecture­especially trabecular number and separation­and overall bone strength were impaired in adults with OI as compared with normative data. Furthermore, we observed various microarchitectural inhomogeneities, most pronounced being trabecular void volumes. Regarding applicability, HR-pQCT could be used without challenges in most adults with OI. However, deviations in scan region may potentially influence HR-pQCT parameters, and standard HR-pQCT analyses may not always give accurate results due to microarchitectural inhomogeneities nor fully reflect all microarchitectural inhomogeneities.

Imaging in osteogenesis imperfecta: Where we are and where we are going.

Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may be confirmed by genetic testing. However, imaging remains pivotal in the evaluation of this disease. The aim of this article is to review the current role played by the various radiologic techniques in the diagnosis and monitoring of OI in the postnatal setting as well as to discuss recent advances and future perspectives in OI imaging. Conventional Radiography and Dual-energy X-ray Absorptiometry (DXA) are currently the two most used imaging modalities in OI. The cardinal radiographic features of OI include generalized osteopenia/osteoporosis, bone deformities, and fractures. DXA is currently the most available technique to assess Bone Mineral Density (BMD), specifically areal BMD (aBMD). However, DXA has important limitations and cannot fully characterize bone fragility in OI based on aBMD. Novel DXA-derived parameters, such as Trabecular Bone Score (TBS), may provide further insight into skeletal changes induced by OI, but evidence is still limited. Techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can be useful as problem-solvers or in specific settings, including the evaluation of cranio-cervical abnormalities. Recent evidence supports the use of High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) as a promising tool to improve the characterization of bone fragility in OI. However, HR-pQCT remains a primarily research technique at present. Quantitative Computed Tomography (QCT) is an alternative to DXA for the determination of BMD at central sites, with distinct advantages but considerably higher radiation exposure. Quantitative Ultrasound (QUS) is a portable, inexpensive, and radiation-free modality that may complement DXA evaluation, providing information on bone quality. However, evidence of usefulness of QUS in OI is poor. Radiofrequency Echographic Multi Spectrometry (REMS) is an emerging non-ionizing imaging method that holds promise for the diagnosis of low BMD and for the prediction of fracture risk, but so far only one published study has investigated its role in OI. To conclude, several different radiologic techniques have proven to be effective in the diagnosis and monitoring of OI, each with their own specificities and peculiarities. Clinicians should be aware of the strategic role of the various modalities in the different phases of the patient care process. In this scenario, the development of international guidelines including recommendations on the role of imaging in the diagnosis and monitoring of OI, accompanied by continuous active research in the field, could significantly improve the standardization of patient care.

Association of Antenatal Evaluations with Postmortem and Genetic Findings in the Series of Fetal Osteogenesis Imperfecta.

INTRODUCTION: Counseling osteogenesis imperfecta (OI) pregnancies is challenging due to the wide range of onsets and clinical severities, from perinatal lethality to milder forms detected later in life. METHODS: Thirty-eight individuals from 36 families were diagnosed with OI through prenatal ultrasonography and/or postmortem clinical and radiographic findings. Genetic analysis was conducted on 26 genes associated with OI in these subjects that emerged over the past 20 years; while some genes were examined progressively, all 26 genes were examined in the group where no pathogenic variations were detected. RESULTS: Prenatal and postnatal observations both consistently showed short limbs in 97%, followed by bowing of the long bones in 89%. Among 32 evaluated cases, all exhibited cranial hypomineralization. Fractures were found in 29 (76%) cases, with multiple bones involved in 18 of them. Genetic associations were disclosed in 27 families with 22 (81%) autosomal dominant and five (19%) autosomal recessive forms, revealing 25 variants in six genes (COL1A1, COL1A2, CREB3L1, P3H1, FKBP10, and IFITM5), including nine novels. Postmortem radiological examination showed variability in intrafamily expression of CREBL3- and P3H1-related OI. CONCLUSION: Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetics, and postmortem evaluation.

Uso de protocolos de examen radiográfico para la evaluación diagnóstica de la osteogénesis imperfecta / Use of radiographic examination protocols for diagnostic evaluation of osteogenesis imperfecta

RESUMEN La osteogénesis imperfecta (OI), también conocida como enfermedad de los huesos de cristal, es una enfermedad rara, causada principalmente por mutaciones en los genes COL1A1 y COL1A2. Aunque el 85-90% de los eventos son causados por mutaciones en el propio colágeno, las formas recesivas pueden ser el resultado de otros defectos. Dado que pueden ocurrir hallazgos similares entre la OI y otras enfermedades, es necesario un diagnóstico diferencial para una adopción más rápida de los tratamientos apropiados. Debido a la necesidad constante de exámenes, estos pacientes tienen más probabilidades de tener complicaciones por la radiación ionizante, por lo que es muy importante cumplir estrictamente con todos los requisitos de protección radiológica. OBJETIVO Verificar la existencia de protocolos de imagen utilizados en el diagnóstico de la OI y describir las técnicas radiográficas involucradas en el proceso. METODOLOGIA Se trata de un estudio cualitativo en el que se utilizaron las revistas PubMed, BIREME, CAPES y ScienceDirect, con el objetivo de verificar la presencia de investigaciones dirigidas a la creación de protocolos de imagen para auxiliar el diagnóstico de la OI. CONSIDERACIONES FINALES: Si bien ha demostrado ser de gran utilidad, debido a los riesgos a los que están expuestos los pacientes con OI, el uso de herramientas que liberan radiaciones ionizantes debe ser monitoreado constantemente. Por lo tanto, los protocolos deben revisarse para que, incluso con una reducción de la dosis, no se pierda la resolución y el detalle de la imagen.

ABSTRACT: The osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare disease, mainly caused by mutations in genes COL1A1 and COL1A2. Although 85-90% of events are caused by mutations in collagen itself, the recessive forms may be the result of other defects. Since similar findings may occur between OI and other diseases, a differential diagnosis is required for faster adoption of appropriate treatments. Due to the constant need for tests, these patients are more likely to have complications due to ionizing radiation, so it is very important to strictly comply with all radiological protection requirements. OBJETIVO To verify the existence of imaging protocols used in the diagnosis of OI and to describe the radiographic techniques involved in the process. METHODOLOGY This is a qualitative study in which PubMed, BIREME, CAPES y ScienceDirect databases were used, with the objective of verifying the presence of research aimed at the creation of imaging protocols to assist in the diagnosis of OI. FINAL CONSIDERATIONS Although it has proved very useful, because of the risks to which patients with OI are exposed, the use of tools that release ionizing radiation should be monitored constantly. With this, the protocols should be reviewed so that even with a dose reduction, the resolution and detail of the image are not lost

Osteogénesis imperfecta. Descripción de 15 casos / Osteogenesis imperfecta. Report of 15 cases

La osteogénesis imperfecta (OI) es un trastorno hereditario del tejido conectivo generalmente relacionado con mutaciones de los genes del colágeno tipoI. El diagnóstico se basa en los hallazgos clínicos y radiológicos. El manejo clínico de la OI en adultos no está del todo establecido y comprende desde la rehabilitación física y los procedimientos quirúrgicos hasta el uso de tratamientos antirresortivos y osteoformadores. El objetivo del presente trabajo ha sido analizar las características clínicas y analíticas de estos pacientes en la edad adulta, así como evaluar los diferentes tratamientos administrados. Se han revisado los casos de OI diagnosticados en nuestro centro en los últimos 12 años (2005-2017). Se describen 15 pacientes adultos con OI

Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered. We reviewed the cases of OI diagnosed in our center over the last 12 years (2005-2017). We describe 15 adult patients with OI

Enfermedad de Pyle: un modelo humano de homeostasis corticotrabecular diferenciada / Pyle's Disease: a human model of differentiated cortical and trabecular homeostasis

La enfermedad de Pyle (OMIN número 265900) es una displasia metafisaria de curso benigno que se hereda con un patrón autosómico recesivo. Se han descrito unos 30 casos genuinos hasta el momento. La causa de este proceso se conoce desde 2016, cuando se descubre su relación con mutaciones en el gen que codifica la proteína sFRP, un conocido inhibidor de la vía Wnt. Se presenta el caso de un varón de 58 años, diagnosticado de enfermedad de Pyle con base en sus características clínicas y radiográficas, cuyo fenotipo muestra un control diferencial de la homeostasis del hueso cortical y trabecular

Pyle's disease (OMIN number 265900) is a metaphyseal dysplasia of benign course, inherited with an autosomal recessive pattern. Some 30 genuine cases have been described so far. The cause of this process has been known since 2016, when its relationship to mutations in the gene encoding the sFRP protein, a known inhibitor of the Wnt pathway, was discovered. We report the case of a 58-year-old man, diagnosed with Pyle's disease based on his clinical and radiographic characteristics, whose phenotype suggested a differential control of cortical and trabecular bone homeostasis

Osteogénesis imperfecta de tipo III en niño ecuatoriano / Osteogenesis imperfecta type III in an Ecuadorian child

Introducción: la osteogénesis imperfecta es una rara enfermedad genética hereditaria caracterizada por su heterogeneidad causada por defectos del tejido conectivo con el rasgo de fragilidad ósea determinante de múltiples fracturas, incluso prenatales; deformidades de huesos largos y columna vertebral y otros síntomas extra-esqueléticos, como escleróticas de color azul, dentinogénesis imperfecta, trastorno de audición y afectación cardiovascular. Objetivo: Presentar un paciente con las características clínicas e imagenológicas de osteogénesis imperfecta de tipo III. Presentación del caso: Niño ecuatoriano de 4 años de edad de baja talla con antecedente de fracturas múltiples desde los 8 meses de nacido, con deformidad en columna vertebral demostrada por radiología por cifoescoliosis en forma de "S" y fracturas vertebrales, con deformidad progresiva en huesos largos; ha sufrido 16 fracturas, no deambula, sensorio presente, orientado en tiempo y espacio, desarrollo cognitivo normal para la edad. La fragilidad ósea del niño según el fenotipo clasifica al diagnóstico de tipo III de osteogénesis imperfecta, el cual es progresivo e invalidante por las deformidades óseas y múltiples fracturas demostradas en exámenes imagenológicos, sin modificaciones en el color de escleróticas, de herencia presumiblemente dominante. Conclusiones: La descripción clínica y radiológica de osteogénesis imperfecta, afección poco conocida, correspondiente al fenotipo III de la enfermedad, reportada en niño ecuatoriano de 4 años de edad, con talla baja que no deambula, expresión de la severidad de su afección genética, con severas alteraciones óseas por su fragilidad con fracturas múltiples en huesos largos y vértebras(AU)

Introduction: Osteogenesis imperfecta is a rare hereditary genetic disease characterized by its heterogeneity caused by connective tissue defects with the feature of bone fragility determining multiple fractures, even prenatal ones; also deformities of long bones and spine, and other extra-skeletal symptoms, such as blue sclerotic, dentinogenesis imperfecta, hearing disorder and cardiovascular affectations. Objective: To present a patient with clinical and radiological findings of osteogenesis imperfect type III. Case presentation: Ecuadorean male child of 4 years old, with a short height, history of multiple fractures from 8 months of age, with spinal deformity demonstrated by radiology due to "S" shaped kyphoscoliosis and vertebral fractures, with progressive deformity in long bones. The boy has suffered 16 fractures, he does not wander, and he is sensory present, oriented in time and space, with normal cognitive development for his age. The bone fragility of the child according to the phenotype classifies in the type III diagnosis of osteogenesis imperfecta, which is progressive and invalidating due to bone deformities and multiple fractures evidenced in imaging tests, without changes in the color of sclerotics and of presumably dominant inheritance. Conclusions: The clinical and radiological description of osteogenesis imperfecta, which is little-known pathology, corresponding to type III phenotype is reported in a 4-year-old boy who, due to his involvement, has a short height and does not wander as a consequence of the severity of bone affectations with fractures in long bones and vertebrae, mainly produced by the fragility of the bones due to his genetic disease(AU)

Osteogénesis imperfecta tipo VII con parto a término. Diagnóstico y manejo / Osteogenesis imperfecta type VII with term birth. Diagnosis and management

Las displasias esqueléticas fetales constituyen un conjunto heterogéneo e infrecuente de anomalías en el crecimiento y desarrollo de las estructuras osteocartilaginosas que resultan en una alteración tanto en la forma como en el tamaño de los huesos largos. La identificación ecográfica de las displasias esqueléticas no es difícil puesto que la medición femoral es una rutina en el exámen ecográfico del feto, pero el diagnóstico diferencial de las mismas es complejo. El estudio genético prenatal ha suspuesto un gran avance en su diagnóstico, basándose de forma práctica la orientación diagnóstica en la determinación de su letalidad. La osteogénesis imperfecta tipo VII es un tipo de displasia ósea severa, infrecuente y de herencia autosómica recesiva. Se manifiesta por una rizomielia con deformidades tempranas sobre todo de miembros inferiores. Presenta fracturas neonatales y su pronóstico es desfavorable, siendo la causa más frecuente de muerte neonatal las complicaciones respiratorias con estrechamiento y compresión torácica. El objetivo de este trabajo es exponer un caso de osteogénesis imperfecta tipo VII y hacer una revisión de las principales displasias esqueléticas. Se discute el diagnóstico y manejo de las mismas

Fetal skeletal dysplasias constitute a heterogeneous and infrequent set of abnormalities in the growth and development of osteocartilaginous structures that result in an alteration in both the shape and size of long bones. The ultrasonographic identification of skeletal dysplasias is not difficult because the femoral measurement is a routine in the ultrasound examination of the fetus, but the differential diagnosis of theme is complex. The prenatal genetic study has shown a great advance in its diagnosis, based in a practical way the diagnostic orientation in the determination of its lethality. Osteogenesis imperfecta type VII is a type of severe, infrequent bone dysplasia with recessive autosomal inheritance. It is manifested by a rhizomyelia with early deformities especially of lower limbs. It presents neonatal fractures and its prognosis is unfavorable, being the most frequent cause of neonatal death the respiratory complications with narrowing and thoracic compression. The objective of this paper is to present a case of osteogenesis imperfecta type VII and to review the main skeletal dysplasias. We discuss the diagnosis and management of them

De la osteología a la osteomiología: tres décadas de aportes originales continuos al análisis biomecánico osteomuscular / From osteology to osteo-myology: three decades of continuous, original contributions to musculoskeletal biomechanical analysis

En consonancia con la orientación tradicional de nuestras investigaciones, la Osteología está incorporando progresivamente el análisis estructural-biomecánico óseo y las interacciones músculo-esqueléticas. En este artículo se sintetizan los aportes originales del CEMFoC a la Osteología moderna en el terreno biomecánico en forma didáctica, para que el lector aprecie sus posibles aplicaciones clínicas. Los hallazgos aportaron evidencias sucesivas en apoyo de dos proposiciones fundamentales: a) los huesos deben interpretarse como estructuras resistivas, biológicamente servocontroladas ("Los huesos tienden siempre a mantener un factor de seguridad que permite al cuerpo trabajar normalmente sin fracturarse" ­ Paradigma de Utah) y b) los huesos interactúan con su entorno mecánico, determinado principalmente por las contracciones musculares, en forma subordinada al entorno metabólico ("Los huesos son lo que los músculos quieren que sean, siempre que las hormonas lo permitan"). Los avances producidos se refieren, tanto cronológica como didácticamente, al conocimiento osteológico en general y al desarrollo de recursos novedosos para el diagnóstico no invasivo de fragilidad ósea, para distinguir entre osteopenias y osteoporosis, y para discriminar entre sus etiologías 'mecánica' y 'sistémica'. Finalmente, el nuevo conocimiento se integra en la proposición de un algoritmo diagnóstico para osteopenias y osteoporosis. El espíritu general de la presentación destaca que la evaluación osteomuscular dinámicamente integrada genera un nuevo espacio de análisis personalizado de los pacientes para la atención de cualquier osteopatía fragilizante con criterio biomecánico. (AU)

In consonance with the traditional spirit of our studies, skeletal research is being progressively focused on the structural-biomechanical analysis of bone and the muscle-bone interactions. In this article, the CEMFoC's members summarize their original findings in bone biomechanics and their potential clinical applications. These findings provided evidence supporting two fundamental hypotheses, namely, A. bones constitute resistive structures, which are biologically servo-controlled ('Bones tend to maintain a safety factor which allows the body to function normally avoiding fractures' ­ the 'Utah paradigm'), and B. the interactions of bones with their mechanical environment mainly are determined by the contraction of local muscles - 'bone-muscle units'), and are subordinated to the control of the metabolic environment ('Bones are what muscles wish them to be, provided that hormones allow for it'). The achievements in the field are presented in a chronological and didactical sequence concerning the general knowledge in Osteology and the development of novel resources for non-invasive diagnosis of bone fragility, aiming to distinguish between osteopenias and osteoporosis and the 'mechanical' and 'metabolic' etiology of these conditions. Finally, the integrated new knowledge is presented as supporting for a proposed diagnostic algorithm for osteopenias and osteoporosis. In general terms, the article highlights the dynamic evaluation of the musculoskeletal system as a whole, opening a new diagnostic field for a personalized evaluation of the patients affected by a boneweakening disease, based on functional and biomechanical criteria. (AU)

Utilidad del Trabecular Bone Score en la valoración del riesgo de fractura osteoporótica / Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic fracture

Introducción y objetivos. El Trabecular Bone Score (TBS) es una técnica de imagen que evalúa el estado de la microarquitectura trabecular. Resultados preliminares sugieren que, junto a la valoración de la densidad mineral ósea, podría mejorar la estimación del riesgo de fractura ostoporótica. El objetivo de este estudio fue analizar los valores de TBS y su relación con las características clínicas, densidad mineral ósea y antecedentes de fracturas en una cohorte de mujeres posmenopáusicas. Material y métodos. Analizamos 2.257 mujeres posmenopáusicas procedentes de la cohorte FRODOS, constituida para determinar los factores de riesgo de fractura osteoporótica mediante una encuesta clínica y densitometría ósea con morfometría vertebral. Se aplicó el TBS a las imágenes densitométricas. Valores de TBS ≤1,230 se consideraron indicativos de microarquitectura degradada. Se realizó una regresión lineal simple y múltiple para determinar los factores asociados con este índice. Resultados. El valor medio de TBS en L1-L4 fue de 1,203±0,121. El 55,3% de las mujeres presentaban valores de microarquitectura degradada. En el análisis de regresión lineal múltiple los factores asociados a los valores bajos de TBS fueron la edad, el peso, la altura, escala T de columna lumbar, tratamiento con glucocorticoides, presencia de diabetes tipo 2 y antecedentes de fractura por fragilidad. Conclusiones. El TBS mostró valores de microarquitectura degradada en las participantes de la cohorte FRODOS y se asoció a factores antropométricos, valor bajo de densidad mineral ósea, presencia de fracturas, antecedentes de diabetes mellitus tipo 2 y uso de glucocorticoides

Introduction and objectives. The trabecular bone score (TBS) is an imaging technique that assesses the condition of the trabecular microarchitecture. Preliminary results suggest that TBS, along with the bone mineral density assessment, could improve the calculation of the osteoporotic fracture risk. The aim of this study was to analyse TBS values and their relationship with the clinical characteristics, bone mineral density and history of fractures of a cohort of posmenopausal women. Material and methods. We analysed 2,257 posmenopausal women from the FRODOS cohort, which was created to determine the risk factors for osteoporotic fracture through a clinical survey and bone densitometry with vertebral morphometry. TBS was applied to the densitometry images. TBS values ≤1230 were considered indicative of degraded microarchitecture. We performed a simple and multiple linear regression to determine the factors associated with this index. Results. The mean TBS value in L1-L4 was 1.203±0.121. Some 55.3% of the women showed values indicating degraded microarchitecture. In the multiple linear regression analysis, the factors associated with low TBS values were age, weight, height, spinal T-score, glucocorticoid treatment, presence of type 2 diabetes and a history of fractures due to frailty. Conclusions. TBS showed microarchitecture degradation values in the participants of the FRODOS cohort and was associated with anthropometric factors, low bone mineral density values, the presence of fractures, a history of type 2 diabetes mellitus and the use of glucocorticoids

Osteogénesis Imperfecta. A propósito de un caso tipo II / Osteogenesis Imperfecta. About a type II case

RESUMEN El síndrome de Osteogénesis Imperfecta (OI) tipo II está dentro del grupo de trastornos del tejido conectivo de origen genético-hereditario que se caracteriza por fragilidad ósea, fracturas múltiples, huesos largos anchos y acortados, además de una pobre mineralización ósea. Su frecuencia de aparición se calcula en aproximadamente 1: 55.000 nacidos vivos y es el resultado de mutaciones de dos genes que codifican las cadenas de colágeno tipo 1. El riesgo de recurrencia es alrededor de 6 % pero si ambos padres fueran heterocigotos, aumentaría a 10-25 %. También se han reportado casos esporádicos por mutación de novo. El diagnóstico se suele realizar por los hallazgos ecográficos en el segundo trimestre o en ecografías previas si los hallazgos son muy evidentes. Las pruebas invasivas son útiles sobretodo en casos de antecedentes familiares con formas leves de OI. En nuestro caso, encontramos durante la ecografía de las 20 semanas una notable hipomineralización de la calota fetal sospechada por hiporrefringencia de la misma, acortamiento de extremidades superiores e inferiores con múltiples fracturas óseas, arcos costales cortos, arqueados y una desproporción toraco-abdominal. En los casos en donde se prosigue con el embarazo más de 60% de los recién nacidos mueren el primer día de vida, el resto lo hace durante el primer mes y la sobrevivencia más allá de un año es rara. La principal causa de muerte postnatal suele ser por falla respiratoria.

SUMMARY Osteogenesis Imperfecta (OI) type II is within the group of connective tissue disorders hereditary genetic-origin characterized by bone fragility, multiple fractures, broad long bones and shortened, and a poor bone mineralization. Their frequency is estimated at approximately 1: 55,000 live births, and is the result of mutations of genes which encoding chains of type 1 collagen. The risk of recurrence is around 6% but if both parents were heterozygous, increase to 10-25%. There has also been reported sporadic cases with de novo mutation. The diagnosis is usually made by ultrasound findings in second trimester or previously if the findings are very obvious. Invasive tests are useful especially in cases of family history with mild forms of OI. In our case, we found during ultrasound 20 weeks a remarkable hypomineralization of fetal calvarial, shortening of upper and lower extremities with multiple bone fractures and short costal arches, arched and thoracoabdominal disproportion. In cases where continued pregnancy more than 60% of newborns die during the first day of life, 80% die in the first month and survival beyond one year is rare. Death can occur prenatally or postnatamente from respiratory failure.

Alternative option for osteogenesis imperfecta and trigeminal neuralgia / Opção alternativa em tratamento da neuralgia do trigêmeo com osteogênese imperfeita

Summary Osteogenesis imperfecta (OI) is a bone disorder that can lead to skull base deformities such as basilar invagination, which can cause compression of cranial nerves, including the trigeminal nerve. Trigeminal neuralgia in such cases remains a challenge, given distorted anatomy and deformities. We present an alternative option, consisting in cannulation of the foramen ovale and classical percutaneous treatment. Percutaneous balloon microcompression was performed in a 28 year-old woman with OI and severe trigeminal neuralgia using computed tomography (CT) and radiographic-guided cannulation of the Gasserian ganglion without neuronavigation or stereotactic devices. The patient developed hypoesthesia on the left V1, V2 and V3 segments with good pain control. This alternative technique with a CT-guided puncture, using angiosuite without the need of any Mayfield clamp, neuronavigation systems, frame or frameless stereotactic devices can be a useful, safe and efficient alternative for patients with trigeminal neuralgia with other bone deforming diseases that severely affect the skull base.

Resumo Osteogênese imperfeita (OI) é uma doença óssea que pode levar a deformidades de base de crânio, como invaginação basilar que pode provocar compressão de nervo craniano, incluindo o nervo trigêmeo. Nestes casos, a neuralgia do trigêmeo permanece como um desafio, pela anatomia distorcida e pelas deformidades. Apresentamos uma alternativa que consiste na canulação do forame oval e no tratamento percutâneo clássico. A microcompressão percutânea por balão foi realizada em uma paciente de 28 anos apresentando OI e grave neuralgia do trigêmeo, sendo realizadas tomografia computadorizada (CT) e canulação guiadas do gânglio gasseriano sem neuronavegação ou dispositivos estereotáxicos. A paciente apresentou hipoestesia à esquerda dos segmentos V1, V2 e V3, com bom controle da dor. Essa técnica alternativa com punção orientada por CT utilizando o angiosuite sem a necessidade de qualquer grampo de Mayfield, sistemas de neuronavegação, ou dispositivos com ou sem arcos estereotáxicos, pode ser uma opção útil, segura e eficiente para pacientes com neuralgia do trigêmeo cursando com outras doenças deformativas que afetem a base craniana de modo grave.

Síndrome de la esclerótica azul: manejo perinatal en un hospital especializado / Blue sclera syndrome: perinatal management in a specialized hospital

RESUMEN La Osteogénesis Imperfecta (OI) se presenta en 1 de cada 20.000 a 1 de cada 60.000 nacimientos. Se trata de un grupo heterogéneo de trastornos, caracterizados por anomalías del colágeno tipo I que interfieren en el proceso normal de osificación del hueso. Debido a lo complejo del manejo del manejo de un niño con OI es recomendable manejar dicho diagnóstico en la etapa fetal de manera a estar preparados tanto los padres como los profesionales para el cuidado y seguimiento, de ahí la importancia de los estudios ecográficos, más los antecedentes genéticos y otros estudios ideales durante el control prenatal de la madre. El ultrasonido es el procedimiento menos invasivo para el diagnóstico prenatal y por lo tanto comporta un menor riesgo utilizarlo. El médico puede examinar el esqueleto del feto buscando curvaturas (torceduras de los huesos de la pierna o el brazo), fracturas, acortamientos o cualquier otra anormalidad ósea que pueda indicar la presencia de OI.Se presenta un caso de OI del Hospital Distrital de Lambaré.

ABSTRACT Osteogenesis Imperfecta (OI) occurs in 1 in 20,000 to 1 in 60,000 births. It is a heterogeneous group of disorders characterized by abnormalities of type I collagen that interfere with the normal process of bone ossification. Due to the complexity of handling the management of a child with OI is advisable to handle that diagnosis in the fetal stage so be prepared both parents and professionals for the care and monitoring, hence the importance of ultrasound studies plus genetic background and other ideals studies during antenatal mother. The ultrasound is less invasive procedure for prenatal diagnosis and therefore is less risky use. The doctor can examine the fetal skeleton looking curvatures (sprained bones of the leg or arm), fractures, bone shortening or other abnormalities that may indicate the presence of OI. A case OI District Hospital of Lambaré is presented.