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1.
J Bone Miner Metab ; 37(5): 768-772, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31079208

RESUMO

Subchondral insufficiency fractures of the femoral head are generally considered to be osteoporosis-related fragility fractures. There have been reports of microfractures being found in subchondral bone on pathological examination. However, the mechanism of these microfractures is not known. In this report, we describe a patient with osteogenesis imperfecta who developed a subchondral insufficiency fracture of the femoral head after a fall that had resulted in a subcapital femoral neck fracture. Bipolar hemiarthroplasty was performed, and bone at the femoral head and neck was sampled for pathophysiological examination. Hematoxylin and eosin staining revealed microfractures and microcallus in the subchondral bone in the femoral head, indicating healing of a subchondral insufficiency fracture before the subcapital femoral neck fracture. Moreover, decreased bone volume and accumulated microdamage were observed in the subchondral bone but not in the cancellous bone in the femoral neck. These findings suggest that subchondral insufficiency fracture of the femoral head is a stress fracture caused by accumulation of microdamage in fragile subchondral bone.


Assuntos
Cabeça do Fêmur/lesões , Fraturas de Estresse/etiologia , Fraturas do Quadril/etiologia , Osteogênese Imperfeita/complicações , Adulto , Osso Esponjoso/patologia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/patologia , Humanos , Masculino , Tamanho do Órgão , Osteogênese Imperfeita/diagnóstico por imagem
2.
J Food Sci ; 84(6): 1646-1650, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31116433

RESUMO

Pepino (Solanum muricatum), which is an evergreen plant native to South America, is well-known for its effects in antioxidation, antidiabetic activity, anti-inflammation, and antitumor activity. A previous study in our lab indicated that Solanum muricatum (SM) extract promoted osteogenic differentiation by upregulating Wnt and BMP signaling pathway in rat bone marrow stromal cells. The osteogenesis imperfecta (OI) mouse model was used in order to further discover the osteogenic properties of SM extract in the present research. We utilized microCT analysis to collect bone mass and microarchitectural parameters at vertebrae and at femur metaphysis in OI mice. Raman spectrometry was applied to identify change of bone mineral and matrix composition during SM treatment. Finally, collagen synthesis marker PINP and collagen degradation marker CTX were detected using enzyme immunoassay. SM extract could improve the bone mass and microarchitectural parameters both at vertebrae and at femur metaphysis. It also significantly increased the collagen content by promoting its biosynthesis and inhibiting its degradation. By using heterozygous Col1a1Jrt /+ mice as a model of OI, 6 weeks treatment of SM extract could significantly ameliorate the symptoms in OI mice. Thus, SM holds potential for developing new drugs of bone formation and bone remodeling.


Assuntos
Osteogênese Imperfeita/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Solanum/química , Animais , Densidade Óssea/efeitos dos fármacos , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteogênese/efeitos dos fármacos , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/metabolismo , Osteogênese Imperfeita/fisiopatologia , Microtomografia por Raio-X
3.
Acta Orthop Belg ; 85(1): 1-11, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31023194

RESUMO

In our country, the sliding Flexible Intramedullary Nailing is used alone or in combination with Ilizarov frame in children with osteogenesis imperfecta. The study assesses the results of sliding intramedullary nailing in deformity correction in severe types of osteogenesis imperfecta. We retrospectively reviewed 17 consecutive cases (mean age 5.2 y.o.) of types III, IV and VII of osteogenesis imperfecta. In group I (9 patients) the transphyseal FIN was performed using titanium nails. Sliding flexible intramedullary nailing was associated with Ilizarov frame in group II in 8 children. Patients in group I had overall complication rate of 88.9%: proximal nail migration (3), early secondary torsional displacement (4), non-telescoping (12), angular deformity (2), delayed or non-union (2). The reoperation rate was 100%. In group II we observed complications in 6 patients: nail migration (2), bowing of femur (2), non-telescoping (3). The reoperation rate was 87.5%. Flexible intramedullary nailing allows realignment and good functional outcomes. Its major disadvantage is an important complication rate and related reoperation rate. The use of Ilizarov frame provides additional stability and allows early weight-bearing.


Assuntos
Fêmur/cirurgia , Fixação Intramedular de Fraturas/métodos , Osteogênese Imperfeita/cirurgia , Adolescente , Pinos Ortopédicos , Criança , Pré-Escolar , Feminino , Fêmur/diagnóstico por imagem , Humanos , Lactente , Ácido Iodoipúrico , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
4.
BMC Musculoskelet Disord ; 20(1): 92, 2019 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30797234

RESUMO

BACKGROUND: Gnathodiaphyseal dysplasia (GDD) is an extremely rare autosomal dominant disease characterized by cemento-osseous lesions in the jawbones, bone fragility, and diaphyseal sclerosis of the tubular bones. Patients with GDD are prone to sustain fractures by minor accidents. Although over 80 cases have been reported, detailed information about the orthopedic treatment of the fractures is limited. CASE PRESENTATION: A 9-year-old Japanese girl with a known history of GDD presented with pain and deformity in the left thigh after a minor fall. She had a displaced transverse fracture in the mid-shaft of the left femur and underwent a closed reduction and external fixation. In the 25th week after the initial surgery, she had another fracture in the left femur at one of the half-pin insertion sites. She underwent an external fixation again. After this operation, the patient sustained another refracture at the same fracture site and one supracondylar fracture at the distant site of the femur. The supracondylar fracture occurred without any triggering activity before beginning a weight-bearing exercise. The supracondylar fracture was successfully treated conservatively, but she sustained two more diaphyseal fractures at half-pin insertion sites one after another. She eventually underwent a revision surgery with a flexible intramedullary nail. At 3 months postoperatively, the fracture was healed and the patient maintained her ambulatory status without further refracture. CONCLUSIONS: Patients with GDD might have narrower safety ranges of biomechanical and physiological drawbacks, which are considered to be acceptable in ordinary cases. The choice of treatment should be aimed at minimizing these negative effects. We recommend intramedullary devise as the first-choice implant for the treatment of isolated femoral shaft fracture in GDD patients in this age group.


Assuntos
Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/métodos , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/cirurgia , Criança , Feminino , Fraturas do Fêmur/etiologia , Fixação Interna de Fraturas/instrumentação , Humanos , Osteogênese Imperfeita/complicações , Recidiva
5.
J Hum Genet ; 64(4): 291-296, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30692598

RESUMO

A rare form of osteogenesis imperfecta (OI) caused by Wingless-type MMTV integration site family 1 (WNT1) mutations combines central nervous system (CNS) anomalies with the characteristic increased susceptibility to fractures. We report an additional case where arachnoid cysts extend the phenotype, and that also confirms the association of intellectual disabilities with asymmetric cerebellar hypoplasia here. Interestingly, if the cerebellum is normal in this disorder, intelligence is as well, analogous to an association with similar delays in a subset of patients with sporadic unilateral cerebellar hypoplasia. Those cases typically appear to represent vascular disruptions, and we suggest that most brain anomalies in WNT1-associated OI have vascular origins related to a role for WNT1 in CNS angiogenesis. This unusual combination of benign cerebellar findings with effects on higher functions in these two situations raises the possibility that WNT1 is involved in the pathogenesis of the associated sporadic cases as well. Finally, our patient reacted poorly to pamidronate, which appears ineffective with this form of OI, so that a lack of improvement is an indication for molecular testing that includes WNT1.


Assuntos
Sistema Nervoso Central/fisiopatologia , Deficiência Intelectual/genética , Osteogênese Imperfeita/genética , Proteína Wnt1/genética , Cistos Aracnóideos/diagnóstico por imagem , Cistos Aracnóideos/fisiopatologia , Sistema Nervoso Central/anormalidades , Sistema Nervoso Central/diagnóstico por imagem , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/fisiopatologia , Mutação , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/fisiopatologia , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/fisiopatologia , Pamidronato/administração & dosagem , Pamidronato/efeitos adversos
6.
J Hum Genet ; 63(7): 811-820, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29636545

RESUMO

We report a Thai father (patient 1) and his daughter (patient 2) affected with osteogenesis imperfecta type IV and dentinogenesis imperfecta. Both were heterozygous for the c.1451G>A (p.Gly484Glu) mutation in COL1A2. The father, a Thai boxer, had very mild osteogenesis imperfecta with no history of low-trauma bone fractures. Scanning electron micrography of the primary teeth with DI of the patient 2, and the primary teeth with DI of another OI patient with OI showed newly recognized dental manifestations of teeth with DI. Normal dentin and cementum might have small areas of ectopic mineralizations. Teeth affected with DI have well-organized ectopic mineralizations in dentin and cementum. The "French-fries-appearance" of the crystals at the cemento-dentinal junction and abnormal cementum have never been reported to be associated with dentinogenesis imperfecta, either isolated or osteogenesis imperfecta-associated. Our study shows for the first time that abnormal collagen fibers can lead to ectopic mineralization in dentin and cementum and abnormal cementum can be a part of osteogenesis imperfecta.


Assuntos
Colágeno Tipo I/genética , Dentinogênese Imperfeita/genética , Mutação , Osteogênese Imperfeita/genética , Adulto , Pré-Escolar , Colágeno Tipo I/metabolismo , Cemento Dentário/diagnóstico por imagem , Cemento Dentário/metabolismo , Cemento Dentário/patologia , Dentina/diagnóstico por imagem , Dentina/metabolismo , Dentina/patologia , Dentinogênese Imperfeita/diagnóstico por imagem , Dentinogênese Imperfeita/metabolismo , Dentinogênese Imperfeita/patologia , Família , Feminino , Expressão Gênica , Heterozigoto , Humanos , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/metabolismo , Osteogênese Imperfeita/patologia , Tailândia , Sequenciamento Completo do Exoma
7.
Rev. clín. esp. (Ed. impr.) ; 218(3): 121-127, abr. 2018. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-174241

RESUMO

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


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fatores de Risco , Densidade Óssea/efeitos da radiação , Glucocorticoides/uso terapêutico , Absorciometria de Fóton/métodos , Pós-Menopausa , Densitometria/métodos , Modelos Lineares , Osteogênese Imperfeita/diagnóstico por imagem , Antropometria/métodos , Análise de Variância , Osteoporose/diagnóstico por imagem
8.
Int J Prosthodont ; 31(2): 138-141, 2018 Mar/Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29518808

RESUMO

This case history report describes the long-term prosthodontic treatment of a patient with gnathodiaphyseal dysplasia (GDD). The patient was initially diagnosed with osteomyelitis in the maxilla in 1986, followed by osteonecrosis spread throughout the mandible. GDD was genetically diagnosed in 2006. Despite the severe alveolar bone resorption, prosthodontic treatment improved the patient's satisfaction and ability to perform essential functions. Regular prosthesis adjustments and periodic follow-up should continue to avoid future complications.


Assuntos
Reabilitação Bucal/métodos , Osteogênese Imperfeita/reabilitação , Adulto , Prótese Dentária Fixada por Implante , Prótese Total , Progressão da Doença , Feminino , Humanos , Osteogênese Imperfeita/diagnóstico por imagem , Radiografia Panorâmica
9.
Med Biol Eng Comput ; 56(9): 1633-1643, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29479660

RESUMO

Vertebral fractures are common in children with osteogenesis imperfecta (OI). Current imaging methods for fracture detection (X-ray and DXA) use ionising radiation. This pilot study explored whether the alteration in blood flow in vertebral fractures results in skin temperature changes that may be detected using high resolution thermal imaging (HRTI) and thus assist diagnosis and monitoring of fractures in OI patients. Eleven participants aged 5-18 years with OI and known vertebral fractures were enrolled. Small metal discs were placed on the skin surface alongside the vertebrae before participants had DXA and X-ray scans and thermal imaging of their backs. Visibility of the discs on the DXA and X-ray scans and thermal images allowed the temperatures of the skin surface above vertebrae without (healthy) and with fractures to be compared to their respective adjacent skin surface regions (region of reference, ROR) by calculating the temperature percentage change (TPC). The TPC between the skin temperature over the fractured thoracic vertebrae (n = 11) and the ROR was significant (1.44%, p = 0.002, 95% confidence). TPC between the skin temperature over healthy thoracic vertebrae and ROR was not significant (0.97%, p = 0.15, 95% confidence). HRTI may provide a novel tool for assisting in detection of vertebral fractures in OI. Graphical abstract • Patients (aged 5-18) with osteogenesis imperfecta and known vertebral fractures. • Thermal imaging was performed alongside routine imaging (DXA scan and spinal X-ray). • The temperature above each vertebra was compared with its adjacent skin region to assist with diagnosis of the fracture.


Assuntos
Imagem Tridimensional , Osteogênese Imperfeita/complicações , Osteogênese Imperfeita/fisiopatologia , Temperatura Cutânea/fisiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/fisiopatologia , Absorciometria de Fóton , Adolescente , Criança , Pré-Escolar , Demografia , Humanos , Osteogênese Imperfeita/diagnóstico por imagem , Fraturas da Coluna Vertebral/complicações , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/fisiopatologia
10.
Mol Med Rep ; 17(3): 4433-4439, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29344653

RESUMO

Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone fragility and fractures, and associated with bone deformity, short stature, dentin, ligament and blue­gray eye sclera. OI is caused by a heterozygous mutation in collagen α­1(I) chain (COL1A1) or collagen α­2(I) chain (COL1A2) genes that encode α chains of type I collagen. Collagen α chain peptide contains an N­propeptide, which has a role in assembly and processing of collagen. Point mutations in the N­propeptide domain appear to trigger OI. In the present study, a novel heterozygous missense mutation, c.281T>A (p.Val94Asp), was identified in the von Willebrand C domain of N­terminal of type I collagen in an individual with type IV OI. The majority of N­terminal mutations are associated with OI/Ehlers­Danlos syndrome (EDS); however, in the present study, the affected individual did not suffer from EDS and the level of serum phosphorus of the patient was low (0.67 mmol/l). A number of clinical phenotypes were observed at the same variation site or in the same region on the polypeptide chain of COL1A, which suggests that additional genetic and environmental factors may influence the severity of OI. The present study may provide insight into the phenotype­genotype association in collagen-associated diseases and improve clinical diagnosis of OI.


Assuntos
Colágeno Tipo I/genética , Osteogênese Imperfeita/diagnóstico , Fósforo/sangue , Sequência de Bases , Criança , Colágeno Tipo I/química , Análise Mutacional de DNA , Estudos de Associação Genética , Humanos , Masculino , Mutação de Sentido Incorreto , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/genética , Linhagem , Estrutura Terciária de Proteína
11.
Metabolism ; 80: 27-37, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28625337

RESUMO

Osteogenesis imperfecta (OI) is the most common inherited form of bone fragility and includes a heterogenous group of genetic disorders which most commonly result from defects associated with type 1 collagen. 85%-90% of cases are inherited in an autosomal dominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects in type 1 collagen. In the last decade, defects in several other proteins involved in the normal processing of type 1 collagen have been described. Recent advances in genetics have called for reconsideration of the classification of OI, however, most recent classifications align with the classic clinical classification by Sillence. The hallmark of the disease is bone fragility but other tissues are also affected. Intravenous bisphosphonates (BPs) are the most widely used intervention, having significant favorable effects regarding areal bone mineral density (BMD) and vertebral reshaping following fractures in growing children. BPs have a modest effect in long bone fracture incidence, their effects in adults with OI concerns only BMD, while there are reports of subtrochanteric fractures resembling atypical femoral fractures. Other therapies showing promising results include denosumab, teriparatide, sclerostin inhibition, combination therapy with antiresorptive and anabolic drugs and TGF-ß inhibition. Gene targeting approaches are under evaluation. More research is needed to delineate the best therapeutic approach in this heterogeneous disease.


Assuntos
Osteogênese Imperfeita/terapia , Adulto , Densidade Óssea , Criança , Humanos , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(6): 797-801, 2017 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-29188603

RESUMO

OBJECTIVE: To explore genetic mutations and clinical features of osteogenesis imperfecta type V. METHODS: Clinical record of five patients (including one familial case) with osteogenesis imperfecta type V were retrospectively analyzed. Peripheral blood samples of the patients, one family member, as well as healthy controls were collected. Mutation of IFITM5 gene was identified by PCR amplification and Sanger sequencing. RESULTS: A heterozygous mutation (c.-14C>T) in the 5-UTR of the IFITM5 gene was identified in all of the patients and one mother. The clinical findings included frequent fractures and spine and/or extremities deformities, absence of dentinogenesis imperfecta, absence of hearing impairment, and blue sclera in 1 case. Radiographic findings revealed calcification of the interosseous membrane between the radius-ulna in all cases. Hyperplastic callus formation was found in 3 cases. Four had radial-head dislocation. CONCLUSION: A single heterozygous mutation c.-14C>T was found in the 5-UTR of the IFITM5 gene in 5 patients with osteogensis imperfecta type V. The patients showed specific radiological features including calcification of interosseous membrane, hyperplastic callus formation, and radial-head dislocation.


Assuntos
Mutação , Osteogênese Imperfeita/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Adulto Jovem
13.
Br J Oral Maxillofac Surg ; 55(9): 971-973, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29037585

RESUMO

To the best of our knowledge, this is the first report to discuss the possible mechanisms of an iatrogenic fracture during operation on an original mandibular fracture in a patient with osteogenesis imperfecta.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Mandibulares/etiologia , Fraturas Mandibulares/cirurgia , Osteogênese Imperfeita/cirurgia , Adulto , Humanos , Doença Iatrogênica , Masculino , Má Oclusão de Angle Classe III/diagnóstico por imagem , Fraturas Mandibulares/diagnóstico por imagem , Osteogênese Imperfeita/diagnóstico por imagem , Radiografia Panorâmica
14.
J Biomech ; 64: 103-111, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-28988680

RESUMO

Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32-65% lower in the OI group (p<0.001). Yield strain did not differ between groups (p≥0.197). In both groups, modulus and strength were lower in the transverse direction (p≤0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p<0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p=0.086). Volumetric bone mineral density was lower in the OI group (p<0.001), but volumetric tissue mineral density was not (p=0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p≤0.024) but not volumetric tissue mineral density (p≥0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI.


Assuntos
Osso e Ossos/fisiopatologia , Fenômenos Mecânicos , Osteogênese Imperfeita/fisiopatologia , Adolescente , Anisotropia , Fenômenos Biomecânicos , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Criança , Elasticidade , Feminino , Análise de Elementos Finitos , Humanos , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Porosidade , Microtomografia por Raio-X
15.
Osteoporos Int ; 28(11): 3277-3280, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28866852

RESUMO

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteogênese Imperfeita/tratamento farmacológico , Adolescente , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Mutação , Osteogênese Imperfeita/complicações , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/genética , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/etiologia , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia
17.
Medicine (Baltimore) ; 96(39): e7783, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953610

RESUMO

Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation.A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis.The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen.We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen.


Assuntos
Colágeno Tipo I/genética , Mutação de Sentido Incorreto , Osteogênese Imperfeita/genética , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Osteogênese Imperfeita/diagnóstico por imagem , Linhagem , Gravidez , Ultrassonografia Pré-Natal
18.
Curr Osteoporos Rep ; 15(5): 419-424, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28808977

RESUMO

PURPOSE OF REVIEW: This review highlights how skeletal dysplasias are diagnosed and how our understanding of some of these conditions has now translated to treatment options. RECENT FINDINGS: The use of multigene panels, using next-generation sequence technology, has improved our ability to quickly identify the genetic etiology, which can impact management. There are successes with the use of growth hormone in individuals with SHOX deficiencies, asfotase alfa in hypophosphatasia, and some promising data for c-type natriuretic peptide for those with achondroplasia. One needs to consider that a patient with short stature has a skeletal dysplasia as options for management may be available.


Assuntos
Osteocondrodisplasias/diagnóstico , Acondroplasia/diagnóstico , Acondroplasia/diagnóstico por imagem , Acondroplasia/tratamento farmacológico , Acondroplasia/genética , Fosfatase Alcalina/uso terapêutico , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/tratamento farmacológico , Doenças do Desenvolvimento Ósseo/genética , Terapia de Reposição de Enzimas , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/diagnóstico por imagem , Hipofosfatasia/tratamento farmacológico , Hipofosfatasia/genética , Imunoglobulina G/uso terapêutico , Natriuréticos/uso terapêutico , Peptídeo Natriurético Tipo C/uso terapêutico , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/tratamento farmacológico , Osteocondrodisplasias/genética , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/genética , Radiografia , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes , Análise de Sequência de DNA , Proteína de Homoeobox de Baixa Estatura/deficiência , Proteína de Homoeobox de Baixa Estatura/genética
20.
Radiol Med ; 122(11): 880-891, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28674909

RESUMO

OBJECTIVE: The purpose of the paper was to assess the morphometric parameters to improve the specificity of the ultrasound (US) signs for the early differential diagnosis between two lethal dysplasias, as thanatophoric dysplasia (TD) and osteogenesis imperfecta type 2 (OI-2). METHOD: The diaphyseal length and the bowed shape of long bones associated with vertebral body dimension assessment were investigated in a group of 14 pregnancy terminations carried out in the time period 2007-2013. The definitive diagnosis was established after pregnancy termination by means of skeletal standardized X-rays, histopathology and gene analysis. RESULTS: TD and OI-2 long bones were significantly shorter than controls. No significant differences were observed between the two dysplasias. The bowing angle was higher in OI-2; a true angulation or eventually axial displacement was present only in the latter. Furthermore, they did not show any evidence of vertebral collapse. The thanatophoric dysplasia presented less bowed long bones, and never true angulation. The spine was steadily characterized by flattened anterior vertebral bodies. CONCLUSION: Long bone shortening is not a sufficient and accurate sign for early sonographic differential diagnosis between TD and OI-2. Angled diaphysis, axial diaphyseal displacement and a conserved vertebral body height in the prenatal period support the diagnosis of osteogenesis imperfecta type 2, while moderately regular bowed diaphysis associated with platyspondyly that of thanatophoric dysplasia.


Assuntos
Osteogênese Imperfeita/diagnóstico por imagem , Diagnóstico Pré-Natal , Displasia Tanatofórica/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Osteogênese Imperfeita/genética , Fenótipo , Reação em Cadeia da Polimerase , Gravidez , Displasia Tanatofórica/genética , Ultrassonografia Pré-Natal , Raios X
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