Osteoporosis in swine / Osteoporose em suínos

Forty-six pigs presented muscle weakness, hind limb paresis and paralysis, weight loss, lateral recumbency, and death in a clinical course of 7 to 10 days. Two pigs were necropsied and exhibited bone fragility, bone callus formation, and multiple fractures in the limbs, ribs, and vertebrae. Microscopically, there was a diffuse and marked decrease in thickness and number of trabeculae. These were disconnected, with a "free-floating" appearance, while the cortex of the long bones was thinned, with an increase of the cortical porosity by enlargement of Haversian canals and endosteal erosion and decreased osteoblastic activity. Flame atomic absorption spectrometry in liver samples revealed significant zinc overload (>2300ppm) and copper deficiency (<33.1ppm). In this communication, we present the first pathologic description of an outbreak of osteoporosis in pigs, and we also provide a brief review of metabolic bone diseases in pigs.

Quarenta e seis suínos apresentaram fraqueza muscular, paresia e paralisia de membros pélvicos, perda de peso, decúbito lateral e morte, com um curso clínico de 7 a 10 dias. Dois suínos foram submetidos a necropsia e exibiram fragilidade óssea, formação de calo ósseo, e múltiplas fraturas em membros, costelas e vértebras. Microscopicamente notou-se difusamente um marcado decréscimo na espessura e número de trabéculas ósseas. Essas estavam desconexas, com uma aparência de flutuação, enquanto o córtex dos ossos longos estava afinado, com um aumento da porosidade pela dilatação dos canais de Haversian, erosão endosteal e diminuição da atividade osteoblástica. Espectrofotometria por chama foi realizada em amostras de fígado, e revelou um excesso de zinco (>2300ppm) e deficiência de cobre (<33.1ppm). Neste trabalho, apresentamos a primeira descrição patológica de um surto de osteoporose em suínos, além de fornecer uma breve revisão de doenças metabólicas em suínos.

Osteoporosis de la posmenopausia: ante el desafío de elegir la estrategia terapéutica / Postmenopausal osteoporosis: facing the challenge of choosing a therapeutic strategy

La osteoporosis de la posmenopausia es una enfermedad crónica y progresiva asociada con un bajo pico de masa ósea o una rápida y persistente pérdida de masa ósea como con-secuencia del déficit de estrógenos endógenos y del envejecimiento. A pesar de que en la actualidad la oferta de medicamentos para su tratamiento en distintas etapas de la vida es muy importante, sigue siendo una enfermedad subdiagnosticada y subtratada a nivel global. La edad, las comorbilidades existentes, los tratamientos concomitantes, el riesgo de caídas, y los antecedentes familiares o personales de fracturas recientes o pasadas tanto como la densidad mineral ósea son factores que deben ser considerados en la evaluación de cada paciente para determinar el grado de riesgo de fractura En aquellos considerados con alto riesgo o riesgo inminente de fractura se recomienda iniciar un tratamiento con algún agente anabólico seguido por un anticatabólico para lograr una rápida reducción del riesgo de fractura. Por último, una adecuada adherencia en el tiempo al tratamiento es clave para alcanzar la mayor eficacia terapéutica dirigida a la reducción de la ocurrencia de fracturas por fragilidad ósea. (AU)

Postmenopausal osteoporosis is a chronic and progressive disease associated with low peak bone mass or a fast and persistent loss of bone mass as a consequence of endogenous estrogen deficiency and aging, and it is an underdiagnosed and undertreated disease worldwide. At present, there is a wide range of drugs available for the treatment of postmenopausal osteoporosis, with appropriate treatments for each phase of this stage of a woman's life. All factors that may increase the risk of bone fragility fracture should be considered at the time of patient assessment. These include age, existing comorbidities, concomitant treatments, risk of falling, family history of fractures or recent or past personal history of fractures, and the results of bone mineral density assessment. In those patients at high risk or imminent risk of fracture, it is recommended to start treatment with an anabolic agent followed by an anticatabolic agent, in order to achieve an immediate reduction of fracture risk. Finally, an adequate adherence to treatment over time will allow achieving the greatest effectiveness of the proposed therapy, which is the reduction of bone fragility fracture events. (AU)

Comprehensive Genetic Analysis of 128 Candidate Genes in a Cohort With Idiopathic, Severe, or Familial Osteoporosis.

CONTEXT: The genetic bases of osteoporosis (OP), a disorder with high heritability, are poorly understood at an individual level. Cases of idiopathic or familial OP have long puzzled clinicians as to whether an actionable genetic cause could be identified. OBJECTIVE: We performed a genetic analysis of 28 cases of idiopathic, severe, or familial osteoporosis using targeted massively parallel sequencing. DESIGN: Targeted sequencing of 128 candidate genes was performed using Illumina NextSeq. Variants of interest were confirmed by Sanger sequencing or SNP array. PATIENTS AND SETTING: Thirty-seven patients in an academic tertiary hospital participated (54% male; median age, 44 years; 86% with fractures), corresponding to 28 sporadic or familial cases. MAIN OUTCOME MEASURE: The identification of rare stop-gain, indel, splice site, copy-number, or nonsynonymous variants altering protein function. RESULTS: Altogether, we identified 28 variants of interest, but only 3 were classified as pathogenic or likely pathogenic variants: COL1A2 p.(Arg708Gln), WNT1 p.(Gly169Asp), and IDUA p.(His82Gln). An association of variants in different genes was found in 21% of cases, including a young woman with severe OP bearing WNT1, PLS3, and NOTCH2 variants. Among genes of uncertain significance analyzed, a potential additional line of evidence has arisen for GWAS candidates GPR68 and NBR1, warranting further studies. CONCLUSIONS: While we hope that continuing efforts to identify genetic predisposition to OP will lead to improved and personalized care in the future, the likelihood of identifying actionable pathogenic variants in intriguing cases of idiopathic or familial osteoporosis is seemingly low.

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: revisión de la literatura actual / Osteogenesis imperfecta: review of current literature

La osteogénesis imperfecta (OI) abarca un grupo de enfermedades de origen genético, caracterizadas por un aumento de la fragilidad ósea, debido a una alteración cualitativa y cuantitativa de la masa ósea, que conlleva un riesgo mayor de recurrencia de fracturas y produce deformidades de diversa magnitud, especialmente en los huesos largos. La incidencia en el ámbito mundial es de aproximadamente 1 en 12 000 a 15 000 nacidos vivos. En nuestro país esta patología es poco conocida y además se lleva un sub-registro de los casos que se presentan. Conclusión: La OI es el trastorno hereditario más común del tejido conectivo; en el 90 % de los casos, se debe a las mutaciones de colágeno tipo I. Los tipos I a V son autosómicos dominantes y del VI al XIII son autosómicos recesivos. Las intervenciones terapéuticas existentes no son curativas. El manejo con bifosfonatos puede mejorar significativamente la historia natural de la enfermedad de tipo III y IV.

Osteogenesis imperfecta (OI) covers a group of diseases of genetic origin, is characterized by an increase in fragility of the bones due to a qualitative and quantitative alteration of bone mass, which entails a higher risk of fractures and produce deformities specially of long bones. The incidence worldwide is approximately 1 in 12,000 to 15,000 live births. In our country this pathology is little known and there is an under-reporting of OI cases. Conclusion: OI is the most common inherited disorder of connective tissue. 90% is due to mutations of type I collagen. Type I to type V are autosomal dominant and type VI to type XIII are autosomal recessive. The existing therapeutic interventions are not curative. Management with bisphosphonates can improve the natural history of type III and type IV disease.

Swimming training potentiates the recovery of femoral neck strength in young diabetic rats under insulin therapy

OBJECTIVE: To test whether swimming training benefits femoral neck strength in young diabetic rats under insulin therapy. METHODS: A total of 60 male Wistar rats (age: 40 days) were divided equally into the following six groups: control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetes was induced with a unique intraperitoneal injection (60 mg/kg body weight) of streptozotocin. Seven days after the injection and after 12 hours of fasting, the animals with blood glucose levels ≥300 mg/dL were considered diabetic. Seven days after the induction of diabetes, the animals in the exercise groups were subjected to progressive swimming training (final week: 90 min/day; 5 days/week; 5% load) for eight weeks. The animals in the insulin groups received a daily dose of insulin (2-4 U/day) for the same period. RESULTS: Severe streptozotocin-induced diabetes reduced the structural properties of the femoral neck (trabecular bone volume, trabecular thickness and collagen fiber content). The femoral neck mechanical properties (maximum load and tenacity) were also impaired in the diabetic rats. Insulin therapy partially reversed the damage induced by diabetes on the structural properties of the bone and mitigated the reductions in the mechanical properties of the bone. The combination of therapies further increased the femoral neck trabecular bone volume (∼30%), trabecular thickness (∼24%), collagen type I (∼19%) and type III (∼13%) fiber contents, maximum load (∼25%) and tenacity (∼14%). CONCLUSIONS: Eight weeks of swimming training potentiates the recovery of femoral neck strength in young rats with severe streptozotocin-induced diabetes under insulin therapy.

Effects of a telescopic intramedullary rod for treating patients with osteogenesis imperfecta of the femur.

PURPOSE: To introduce a new model of telescopic intramedullary rod (TIR), evaluate its effects on treating patients presenting with moderate and severe osteogenesis imperfecta (OI) and to compare the findings with those of other telescopic rods. METHODS: A total of 21 patients (nine girls and 12 boys; mean age at first operation, 6.6 years, 1.52 to 13.18) who underwent 52 femoral operations were monitored during a mean of 9.96 years (3.39 to 14.54). Patient characteristics, telescoping rod capability and its complications were examined. RESULTS: According to the Sillence classification, we investigated one patient with type I, nine with type III and 11 with type IV OI. Revision rates at up to five years (36%) were inferior to those found for the Fassier-Duval rod (46%). The main cause of revision was fracture (15 patients), followed by rod migration (nine), and infection (two). The rod exhibited higher telescopic capacity in boys than girls. Type III most commonly required an operation; the age group with the highest number of procedures was five to ten years. Male migration was the main cause of rod migration. CONCLUSION: The TIR has a satisfactory cost-benefit ratio with less complication rates and low production costs. The TIR is a feasible alternative to the commonly used Fassier-Duval rod. LEVEL OF EVIDENCE: IV.

Osteogênese Imperfeita em cão jovem da raça pinscher / Osteogenesis Imperfect in an young pinscher dog

Background: Osteogenesis imperfecta is a severe genetic disease rarely described in veterinary medicine. This multisystemic condition is caused by a defect in the production and metabolization of collagen, which implicates in bone fragility. This disease has been described in cattle, sheep, domestic felines, mouse and dogs of different breeds, including collie, golden retriever, beagle, dachshund and chow chow. Animals affected by this condition present multiple fractures without previous occurrence of trauma. Therefore, this report aimed to describe a case of osteogenesis imperfecta type III in a miniature pinscher dog.Case: A 1-year-old male miniature pinscher dog, was admitted for clinical evaluation in Fortaleza, Brazil, with a history of spontaneous fractures without known causes. This animal was maintained indoors, fed on dry feed and presented recurrent events of claudication and pain. In the physical examination, the individual walked solely with the forelimbs, avoiding the use of the hind limbs and presented pain behavior. Bulging of the skull was observed laterally, which promoted a triangular appearance of head and face. Fontanelles were soft, and the eyes presented blueish sclera and corneal opacity. Teeth were small, translucid, fragile and deformed. Radiography images revealed bulging of the calvaria and persistent fontanelles with open cranial sutures. In addition, cranial convolutions were less clear, which was compatible with hydrocephalus. Dental roots were narrow, short and presented partial pulp obliteration. The radiographic contrast of the dentin was low with a reduction of periapical radiolucency. Bone radiopacity was low in the bones of the abdomen and pelvis, in addition to femur. Metaphysis of the right tibia was enlarged and angular. Multiple fractures were identified in the pelvis with the formation of opaque bony calluses and bone marrow sclerosis. Physiological parameters and blood test results were unaltered.[...]

Osteogênese Imperfeita em cão jovem da raça pinscher / Osteogenesis Imperfect in an young pinscher dog

Background: Osteogenesis imperfecta is a severe genetic disease rarely described in veterinary medicine. This multisystemic condition is caused by a defect in the production and metabolization of collagen, which implicates in bone fragility. This disease has been described in cattle, sheep, domestic felines, mouse and dogs of different breeds, including collie, golden retriever, beagle, dachshund and chow chow. Animals affected by this condition present multiple fractures without previous occurrence of trauma. Therefore, this report aimed to describe a case of osteogenesis imperfecta type III in a miniature pinscher dog.Case: A 1-year-old male miniature pinscher dog, was admitted for clinical evaluation in Fortaleza, Brazil, with a history of spontaneous fractures without known causes. This animal was maintained indoors, fed on dry feed and presented recurrent events of claudication and pain. In the physical examination, the individual walked solely with the forelimbs, avoiding the use of the hind limbs and presented pain behavior. Bulging of the skull was observed laterally, which promoted a triangular appearance of head and face. Fontanelles were soft, and the eyes presented blueish sclera and corneal opacity. Teeth were small, translucid, fragile and deformed. Radiography images revealed bulging of the calvaria and persistent fontanelles with open cranial sutures. In addition, cranial convolutions were less clear, which was compatible with hydrocephalus. Dental roots were narrow, short and presented partial pulp obliteration. The radiographic contrast of the dentin was low with a reduction of periapical radiolucency. Bone radiopacity was low in the bones of the abdomen and pelvis, in addition to femur. Metaphysis of the right tibia was enlarged and angular. Multiple fractures were identified in the pelvis with the formation of opaque bony calluses and bone marrow sclerosis. Physiological parameters and blood test results were unaltered.[...](AU)

Biomecánica de las fracturas por stress / Biomechanical features of stress fractures

Se define como estrés (stress) tanto la fuerza que una carga externa ejerce sobre un cuerpo sólido como la fuerza reactiva que acompaña a la primera (Ley de Newton), por unidad de área imaginaria transversal a su dirección. Las cargas internas reactivas inducen deformaciones proporcionales del cuerpo. La resistencia del cuerpo a deformarse se llama rigidez. La deformación puede resquebrajar el cuerpo y, eventualmente, producir una fractura por confluencia de trazos. La resistencia del cuerpo a separarse en fragmentos por esa causa se llama tenacidad. La resistencia del cuerpo a la fractura es proporcional al stress que puede soportar sin separarse en fragmentos por deformación (no hay fractura sin deformación y sin stress previo). El stress máximo que un cuerpo puede soportar sin fracturarse resulta de una combinación de ambas propiedades: rigidez y tenacidad, cada una con distintos determinantes biológicos. Una o varias deformaciones del cuerpo pueden provocarle resquebrajaduras sin fracturarlo. La acumulación de resquebrajaduras determina la "fatiga" del material constitutivo del cuerpo, que reduce su rigidez, tenacidad y resistencia a la fractura para la próxima ocasión ("fragilidad por fatiga"). En el caso de los huesos, en general, los términos stress y fatiga tienen las connotaciones amplias referidas, respecto de todas las fracturas posibles. La fatiga predispone a fracturas a cargas bajas, que se denominan (correctamente) "fracturas por fatiga" y también (incorrectamente) "fracturas por stress", para distinguirlas de las que ocurren corrientemente, sin resquebrajaduras previas al trauma, que se denominan (incorrectamente) "fracturas por fragilidad, o por insuficiencia". En realidad, todas las fracturas se producen por stress y por fragilidad o insuficiencia (en conjunto); pero la distinción grosera entre fracturas "por fatiga, o por stress", por un lado, y "por fragilidad" o "por insuficiencia", por otro, aceptando las amplias connotaciones referidas antes, tiene valor en la práctica clínica. Este artículo intenta explicar esas particularidades biomecánicas y describir las distintas condiciones que predisponen a las fracturas "por fatiga o por stress" en la clínica, distinguiéndolas de las fracturas "por fragilidad o por insuficiencia" (manteniendo estas denominaciones) y detallando las características de interés directo para su diagnóstico y tratamiento. (AU)

The term "stress" expresses the force exerted by an external load on a solid body and the accompanying, opposed force (Newton's Law), expressed per unit of an imaginary area perpendicular to the loading direction. The internal loads generated this way deform (strain) proportionally the body's structure. The resistance of the body to strain expresses its stiffness. Critical strain magnitudes may induce micro-fractures (microdamage), the confluence of which may fracture the body. The body's resistance to separation into fragments determines its toughness. Hence, the body's resistance to fracture is proportional to the stress the body can support (or give back) while it is not fractured by the loadinduced strain (no stress, no strain -> no fracture). Therefore, the maximal stress the body can stand prior to fracture is determined by a combination of both, its stiffness and its toughness; and each of those properties is differently determined biologically. One or more deformations of the body may induce some microdamage but not a fracture. Microdamage accumulation determines the fatigue of the material constitutive of the body and reduces body's toughness, leading to a "fatigue-induced fragility". In case of bones, in general, both stress and fatigue have the referred, wide connotations, regarding any kind of fractures. In particular, bone fatigue predisposes to low-stress fractures, which are named (correctly) "fatigue fractures" and also misnamed "stress fractures", to distinguish them from the current fractures that occur without any excess of microdamage, that are named (wrongly) "fragility" or "insufficiency" fractures. In fact, all fractures result from all stress and fragility or insufficiency as a whole; however, the gross distinction between "fatigue or stress fractures", on one side, and "fragility or insufficiency fractures", on the other, accepting the wide connotations of the corresponding terminology, is relevant to clinical practice. This article aims to explain the above biomechanical features and describe the different instances that predispose to "fatigue or stress fractures" in clinical practice, as a different entity from "insufficiency or fragility fractures" (maintaining this nomenclature), and describe their relevant features to their diagnosis and therapy. (AU)

New insights on diabetes and bone metabolism / Novos conceitos em diabetes e metabolismo ósseo

Diabetes mellitus is a common chronic metabolic disease worldwide whose prevalence has increased during the last decades. Besides its more commonly recognized complications, such as macrovascular disease, retinopathy, nephropathy and neuropathy, diabetes related bone disease has gained growing attention. Diabetic patients are more prone to fracture than the general population as well as to low turnover bone disease in the chronic kidney disease setting. In this review, we discuss the relationship between diabetes and bone as well as the pathogenesis of bone fragility in T2D.

Resumos O diabetes mellitus é uma desordem metabólica crônica cuja prevalência tem aumentado no mundo todo ao longo das últimas décadas. Além de suas complicações mais reconhecidas, como a doença macrovascular, retinopatia, nefropatia e neuropatia, as alterações ósseas relacionadas ao diabetes têm ganhado um crescente interesse. Os pacientes diabéticos são mais suscetíveis a fraturas do que a população geral e à doença de baixa remodelação entre os pacientes com doença renal crônica. Nesta revisão, iremos discutir a relação entre diabetes e o tecido ósseo, assim como a patogênese da fragilidade óssea no diabetes tipo 2.

Pore cross-section area on predicting elastic properties of trabecular bovine bone for human implants.

A clear understanding of the dependence of mechanical properties of bone remains a task not fully achieved. In order to estimate the mechanical properties in bones for implants, pore cross-section area, calcium content, and apparent density were measured in trabecular bone samples for human implants. Samples of fresh and defatted bone tissue, extracted from one year old bovines, were cut in longitudinal and transversal orientation of the trabeculae. Pore cross-section area was measured with an image analyzer. Compression tests were conducted into rectangular prisms. Elastic modulus presents a linear tendency as a function of pore cross-section area, calcium content and apparent density regardless of the trabecular orientation. The best variable to estimate elastic modulus of trabecular bone for implants was pore cross-section area, and affirmations to consider Nukbone process appropriated for marrow extraction in trabecular bone for implantation purposes are proposed, according to bone mechanical properties. Considering stress-strain curves, defatted bone is stiffer than fresh bone. Number of pores against pore cross-section area present an exponential decay, consistent for all the samples. These graphs also are useful to predict elastic properties of trabecular samples of young bovines for implants.