RESUMEN
BACKGROUND: For children with Osteogenesis Imperfecta (OI), a rare genetic bone disease, walking can be difficult to carry out due to a combination of bone fragility and deformity, muscle weakness, joint hypermobility, and pain. Bisphosphonate treatment has facilitated more children being able to walk, but for many, foot and ankle hypermobility is a limiting factor. Current evidence on foot orthoses in children with OI is sparse. This study aimed to evaluate gait characteristics in children with OI walking barefoot as compared to walking with foot orthoses. METHODS: Twenty-three children with OI and hypermobility (mean age 8.3 ± 3.0 years) were included in this cross-sectional study. Children conducted three-dimensional gait analysis barefoot, and with foot orthoses and appropriate foot wear (stable yet light-weight), respectively. Walking speed, step length, lower limb kinematics and kinetics were collected. Differences in gait characteristics between test conditions were evaluated using paired sample t-tests. RESULTS: When walking with foot orthoses, the external foot progression angle was reduced, peak ankle dorsiflexion angle increased, and peak plantarflexion moment increased as compared to barefoot. No difference was found in walking speed between test conditions, however, children with OI walked with longer steps with foot orthoses as compared to barefoot. CONCLUSION: The observed gait alterations suggest that foot orthoses, aiming to support the foot and ankle joint, contributed to reduced overall foot rotation as measured by external foot progression, increased peak plantarflexion moment, and increased step length. In a wider perspective, the ability to walk provides the opportunity to be physically active, and thereby increase skeletal loading and prevent fractures, thus, foot orthoses may be an important treatment option to consider in children with OI. LEVEL OF EVIDENCE: III.
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Ortesis del Pié , Marcha , Osteogénesis Imperfecta , Humanos , Osteogénesis Imperfecta/terapia , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/fisiopatología , Estudios Transversales , Niño , Femenino , Masculino , Fenómenos Biomecánicos , Preescolar , Adolescente , Caminata/fisiología , Análisis de la Marcha , Inestabilidad de la Articulación/fisiopatología , Inestabilidad de la Articulación/terapia , Inestabilidad de la Articulación/diagnósticoAsunto(s)
Absorciometría de Fotón , Anticuerpos Monoclonales , Conservadores de la Densidad Ósea , Densidad Ósea , Hueso Esponjoso , Osteogénesis Imperfecta , Humanos , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Osteogénesis Imperfecta/tratamiento farmacológico , Osteogénesis Imperfecta/fisiopatología , Osteogénesis Imperfecta/diagnóstico por imagen , Absorciometría de Fotón/métodos , Femenino , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/farmacología , Hueso Esponjoso/fisiopatología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/efectos de los fármacos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Masculino , Adulto , Vértebras Lumbares/fisiopatología , Persona de Mediana EdadRESUMEN
OBJECTIVES: The aim of the study was to assess the muscoloskeletal system and spatiotemporal gait parameters of patients in three types of osteogenesis imperfecta. DESIGN STUDY: Retrospective observational study. SETTINGS: The Department of Rehabilitation, Children's Memorial Health Institute in Warsaw, Poland. PARTICIPANTS: This study investigated individuals with various types of osteogenesis imperfecta: 33 with osteogenesis imperfecta I (aged 13.9), 16 with osteogenesis imperfecta III (aged 10.4), and 14 with osteogenesis imperfecta IV (aged, 15.8), as well as a reference group of 400 healthy individuals. MAIN MEASURES: The musculoskeletal assessment included: medical record review, clinical evaluation, functional tests, long bone deformity assessment via clinical and X-ray examination, and objective gait analysis with the Vicon Motion Systems (Ltd, Oxford, UK). RESULTS: The study revealed notable differences in clinical presentation, deformities within the musculoskeletal system, gait parameters across the various types of osteogenesis imperfecta (p < 0.001). The most affected gait parameters were: cadence, gait speed and step length. The greatest deformities of lower limbs and spine were presented in patients with osteogenesis imperfecta type III. CONCLUSIONS: These findings are significant for understanding gait abnormalities in osteogenesis imperfecta patients and designing customized physiotherapy programs to help them participate fully in daily life. Improvement of muscle strength is one of the key for easier engagement in activities like walking or stair-climbing.
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Marcha , Osteogénesis Imperfecta , Humanos , Osteogénesis Imperfecta/fisiopatología , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/rehabilitación , Masculino , Femenino , Adolescente , Niño , Estudios Retrospectivos , Marcha/fisiología , Análisis de la Marcha , Sistema Musculoesquelético/fisiopatología , PoloniaRESUMEN
Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. METHODS: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. RESULTS: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. CONCLUSION: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.
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Conservadores de la Densidad Ósea , Densidad Ósea , Difosfonatos , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Mutación , Humanos , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Densidad Ósea/fisiología , Densidad Ósea/genética , Femenino , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/farmacología , Masculino , Difosfonatos/uso terapéutico , Difosfonatos/farmacología , Adulto , Estudios de Seguimiento , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/fisiopatología , Osteogénesis Imperfecta/tratamiento farmacológico , Osteogénesis Imperfecta/complicaciones , Adolescente , Adulto Joven , Persona de Mediana Edad , NiñoRESUMEN
Pediatric patients with Osteogenesis Imperfecta (OI), a heritable connective tissue disorder, frequently suffer from long bone deformations. Surgical correction often results in bone non-unions, necessitating revision surgery with autogenous bone grafting using bone-marrow-derived stem cells (BM-SC) to regenerate bone. BM-SC harvest is generally invasive and limited in supply; thus, adipose tissue's stromal vascular fraction (SVF) has been introduced as an alternative stem cell reservoir. To elucidate if OI patients' surgical site dissected adipose tissue could be used as autologous bone graft in future, we investigated whether the underlying genetic condition alters SVF's cell populations and in vitro differentiation capacity. After optimizing SVF isolation, we demonstrate successful isolation of SVF of pediatric OI patients and non-OI controls. The number of viable cells was comparable between OI and controls, with about 450,000 per gram tissue. Age, sex, type of OI, disease-causing collagen mutation, or anatomical site of harvest did not affect cell outcome. Further, SVF-containing cell populations were similar between OI and controls, and all isolated SVF's demonstrated chondrogenic, adipogenic, and osteogenic differentiation capacity in vitro. These results indicate that SVF from pediatric OI patients could be used as a source of stem cells for autologous stem cell therapy in OI.
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Tejido Adiposo/citología , Osteogénesis Imperfecta/fisiopatología , Células del Estroma/citología , Adipogénesis , Tejido Adiposo/metabolismo , Adolescente , Niño , Preescolar , Condrogénesis , Colágeno/genética , Colágeno/metabolismo , Femenino , Humanos , Masculino , Mutación , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/metabolismo , Células del Estroma/metabolismo , Fracción Vascular Estromal/metabolismo , Adulto JovenRESUMEN
INTRODUÇÃO: A OI é uma doença genética caracterizada por fragilidade óssea e fraturas recorrentes por mínimo trauma, além de deformidades de ossos longos e, nos casos mais graves, consequente incapacidade funcional para deambulação. Além do tratamento medicamentoso para aumentar densidade mineral óssea, cirurgias ortopédicas com inserção de dispositivos intramedulares são indicadas para corrigir as deformidades e estabilizar as fraturas. Entre estes dispositivos implantáveis disponíveis estão: fios (Kirschner ou Steinmann) e hastes (flexíveis ou extensíveis). Com o objetivo de alinhar os ossos longos prevenindo e corrigindo curvaturas que propiciem fraturas, a escolha por haste extensível, também chamada telescópica, para criança ou adolescente ainda em fase de crescimento se justifica por sua capacidade de se estender, acompanhando o crescimento ósseo e, possivelmente, reduzindo o número de revisões cirúrgicas para substituição do implante. Contudo, apesar da evolução das hastes extensíveis ao longo dos anos, chegando ao atual modelo Fassier Duval (FD), complicações pós-operatórias podem ocorrer e demandar revisão cirúrgica, assim como ocorre com as hastes e os dispositivos não extensíveis. TECNOLOGIA: Hastes intramedulares telescópicas (extensíveis). PERGUNTA: O uso de hastes intramedulares telescópicas (extensíveis, tipo Fassier Duval) é seguro e eficaz para correção de deformidades ósseas, redução das incidências de fraturas, revisões e complicações cirúrgicas, além de incremento dos resultados de
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Niño , Adolescente , Dispositivos de Fijación Ortopédica , Aparatos Ortopédicos , Osteogénesis Imperfecta/fisiopatología , Desarrollo Infantil , Desarrollo del Adolescente , Fracturas Óseas/prevención & control , Fijación de Fractura/métodos , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economíaAsunto(s)
Alargamiento Óseo/métodos , Escoliosis , Fusión Vertebral/métodos , Tracción , Cuidados Posteriores , Niño , Progresión de la Enfermedad , Femenino , Humanos , Fijadores Internos , Limitación de la Movilidad , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/fisiopatología , Radiografía Torácica/métodos , Escoliosis/diagnóstico , Escoliosis/etiología , Curvaturas de la Columna Vertebral/diagnóstico por imagen , Curvaturas de la Columna Vertebral/etiología , Tracción/instrumentación , Tracción/métodosRESUMEN
Osteogenesis imperfecta (OI) is a genetic disorder that features wide-ranging defects in both skeletal and nonskeletal tissues. Previously, we and others reported that loss-of-function mutations in FK506 Binding Protein 10 (FKBP10) lead to skeletal deformities in conjunction with joint contractures. However, the pathogenic mechanisms underlying joint dysfunction in OI are poorly understood. In this study, we have generated a mouse model in which Fkbp10 is conditionally deleted in tendons and ligaments. Fkbp10 removal substantially reduced telopeptide lysyl hydroxylation of type I procollagen and collagen cross-linking in tendons. These biochemical alterations resulting from Fkbp10 ablation were associated with a site-specific induction of fibrosis, inflammation, and ectopic chondrogenesis followed by joint deformities in postnatal mice. We found that the ectopic chondrogenesis coincided with enhanced Gli1 expression, indicating dysregulated Hedgehog (Hh) signaling. Importantly, genetic inhibition of the Hh pathway attenuated ectopic chondrogenesis and joint deformities in Fkbp10 mutants. Furthermore, Hh inhibition restored alterations in gait parameters caused by Fkbp10 loss. Taken together, we identified a previously unappreciated role of Fkbp10 in tendons and ligaments and pathogenic mechanisms driving OI joint dysfunction.
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Condrocitos/patología , Articulaciones/fisiopatología , Actividad Motora , Osteogénesis Imperfecta/fisiopatología , Osteogénesis , Proteínas de Unión a Tacrolimus/metabolismo , Animales , Animales Recién Nacidos , Condrogénesis/genética , Colágeno Tipo I/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Marcha , Eliminación de Gen , Regulación de la Expresión Génica , Proteínas Hedgehog/metabolismo , Hidroxilación , Inflamación/genética , Inflamación/patología , Articulaciones/patología , Ligamentos/patología , Lisina/metabolismo , Ratones , Modelos Biológicos , Osificación Heterotópica/complicaciones , Osificación Heterotópica/genética , Osificación Heterotópica/patología , Osificación Heterotópica/fisiopatología , Osteogénesis/genética , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Péptidos/metabolismo , Análisis de Secuencia de ARN , Transducción de Señal , Proteínas de Unión a Tacrolimus/genética , Tendones/patologíaRESUMEN
Osteogenesis imperfecta (OI) is a bone fragility disorder that is usually caused by mutations affecting collagen type I. We compared the calvaria bone tissue transcriptome of male 10-week-old heterozygous Jrt (Col1a1 mutation) and homozygous oim mice (Col1a2 mutation) to their respective littermate results. We found that Jrt and oim mice shared 185 differentially expressed genes (upregulated: 106 genes; downregulated: 79 genes). A total of seven genes were upregulated by a factor of two or more in both mouse models (Cyp2e1, Slc13a5, Cgref1, Smpd3, Ifitm5, Cthrc1 and Rerg). One gene (Gypa, coding for a blood group antigen) was downregulated by a factor of two or more in both OI mouse models. Overrepresentation analyses revealed that genes involved in 'ossification' were significantly overrepresented among upregulated genes in both Jrt and oim mice, whereas hematopoietic genes were downregulated. Several genes involved in Wnt signaling and transforming growth factor beta signaling were upregulated in oim mice, but less so in Jrt mice. Thus, this study identified a set of genes that are dysregulated across various OI mouse models and are likely to play an important role in the pathophysiology of this disorder.
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Osteogénesis Imperfecta/genética , Cráneo/metabolismo , Animales , Colágeno Tipo I/genética , Transportadores de Ácidos Dicarboxílicos/metabolismo , Modelos Animales de Enfermedad , Fémur/metabolismo , Perfilación de la Expresión Génica/métodos , Heterocigoto , Homocigoto , Masculino , Ratones , Mutación , Osteogénesis , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/fisiopatología , Cráneo/fisiología , Esfingomielina Fosfodiesterasa/metabolismo , Simportadores/metabolismo , Transcriptoma/genéticaRESUMEN
Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle-bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the pathogenesis of the skeletal muscle weakness in relation to the bone pathogenesis of OI in light of the critical role of muscle-bone crosstalk is essential to developing and identifying novel therapeutic targets and strategies for OI. This review will highlight how impaired skeletal muscle function contributes to the pathophysiology of OI and how this phenomenon further perpetuates bone fragility.
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Huesos/patología , Debilidad Muscular/patología , Músculo Esquelético/patología , Osteogénesis Imperfecta/patología , Animales , Fenómenos Biomecánicos , Huesos/fisiopatología , Metabolismo Energético , Humanos , Debilidad Muscular/fisiopatología , Músculo Esquelético/fisiopatología , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/fisiopatologíaRESUMEN
Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap-/- mice also had altered numbers of CD146+CD200+ and CD146-CD200+ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap-/- mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-ß, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice - a phenotype that correlates with the tendon pathology.
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Tendón Calcáneo/patología , Proteínas de la Matriz Extracelular/deficiencia , Actividad Motora , Osteogénesis Imperfecta/patología , Osteogénesis Imperfecta/fisiopatología , Ligamento Rotuliano/patología , Tendón Calcáneo/metabolismo , Actinas/metabolismo , Factores de Edad , Animales , Modelos Animales de Enfermedad , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Proteínas de la Matriz Extracelular/genética , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Genes Recesivos , Predisposición Genética a la Enfermedad , Fuerza de la Mano , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Chaperonas Moleculares/genética , FN-kappa B/metabolismo , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/metabolismo , Ligamento Rotuliano/metabolismo , Fenotipo , Fosforilación , Resistencia Física , Células Madre/metabolismo , Células Madre/patologíaAsunto(s)
Predisposición Genética a la Enfermedad , Trastornos del Neurodesarrollo/genética , Osteogénesis Imperfecta/genética , Proteínas de Transporte Vesicular/genética , Alelos , Niño , Preescolar , Femenino , Humanos , Masculino , Mutación Missense/genética , Trastornos del Neurodesarrollo/fisiopatología , Osteogénesis Imperfecta/fisiopatologíaRESUMEN
Patient-reported outcome measures (PROMs) are increasingly utilized as endpoints in clinical trials. The Short Form Health Survey-12 (SF-12v2) is a generic PROM for adults. We sought to evaluate the validity of SF-12v2 in adults with osteogenesis imperfecta (OI). Physical and mental health-related quality of life (HRQoL) were assessed in a large cohort of adults in a multicenter, observational, natural history study. Physical HRQoL scores were correlated with the Gillette Functional Assessment Questionnaire (GFAQ). We calculated sample sizes required in clinical trials with crossover and parallel-group designs to detect clinically meaningful changes in physical HRQoL. Three hundred and two adults with OI types I, III, and IV were enrolled. Physical HRQoL scores in the study population were lower than population norms. Physical HRQoL scores moderately correlated with GFAQ for OI types I and IV. We found no correlations between mental and physical HRQoL. From a clinical trial readiness perspective, we show that SF-12v2 reliably measures physical function in adults with OI and can be utilized in crossover trials to detect meaningful physical HRQoL changes with small sample sizes. This study shows that SF-12v2 can be used to measure changes in physical HRQoL in response to interventions in OI.
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Osteogénesis Imperfecta/fisiopatología , Osteogénesis Imperfecta/psicología , Adulto , Estudios de Cohortes , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios/estadística & datos numéricos , Adulto JovenRESUMEN
Osteogenesis imperfecta (OI or brittle bone disease) is a group of genetic disorders of the connective tissues caused mainly by mutations in the genes encoding collagen type I. Clinical manifestations of OI include skeletal fragility, bone deformities, and severe functional disabilities, such as hearing loss. Progressive hearing loss, usually beginning in childhood, affects approximately 70% of people with OI with more than half of the cases involving the inner ear. There is no cure for OI nor a treatment to ameliorate its corresponding hearing loss, and very little is known about the properties of OI ears. In this study, we investigate the morphology of the otic capsule and the cochlea in the inner ear of the oim mouse model of OI. High-resolution 3D images of 8-week old oim and WT inner ears were acquired using synchrotron microtomography. Volumetric morphometric measurements were conducted for the otic capsule, its intracortical canal network and osteocyte lacunae, and for the cochlear spiral ducts. Our results show that the morphology of the cochlea is preserved in the oim ears at 8 weeks of age but the otic capsule has a greater cortical thickness and altered intracortical bone porosity, with a larger number and volume density of highly branched canals in the oim otic capsule. These results portray a state of compromised bone quality in the otic capsule of the oim mice that may contribute to their hearing loss.
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Oído Interno/diagnóstico por imagen , Oído Interno/fisiopatología , Osteogénesis Imperfecta/fisiopatología , Animales , Densidad Ósea , Cóclea/diagnóstico por imagen , Cóclea/fisiopatología , Modelos Animales de Enfermedad , Tomografía con Microscopio Electrónico/métodos , Osteón/diagnóstico por imagen , Osteón/fisiopatología , Masculino , Ratones Mutantes , Osteogénesis Imperfecta/etiología , SincrotronesRESUMEN
Alendronate (Aln) has been the first-line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three-week-old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR- and Aln-treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.
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Alendronato/farmacología , Conservadores de la Densidad Ósea/farmacología , Osteogénesis Imperfecta , Osteogénesis/efectos de los fármacos , Tiofenos/farmacología , Animales , Densidad Ósea/efectos de los fármacos , Resorción Ósea/fisiopatología , Modelos Animales de Enfermedad , Femenino , Fémur/efectos de los fármacos , Fémur/fisiología , Curación de Fractura/efectos de los fármacos , Ratones , Osteogénesis Imperfecta/patología , Osteogénesis Imperfecta/fisiopatologíaRESUMEN
This article is the sixth in a series on the biological basis of child health. It provides an overview of the development of the skeletal system before and after birth, and outlines the potential congenital anomalies that may occur. The article explains the structure and function of the bones before describing the role of the joints, tendons and ligaments. It also outlines the presentation and management of some of the common orthopaedic conditions seen in infants and children, including fractures, osteogenesis imperfecta, scoliosis, juvenile idiopathic arthritis, developmental dysplasia of the hip and achondroplasia.
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Huesos/fisiopatología , Crecimiento y Desarrollo/fisiología , Enfermedades Musculoesqueléticas/terapia , Huesos/cirugía , Salud Infantil , Preescolar , Femenino , Fracturas Óseas/fisiopatología , Fracturas Óseas/terapia , Luxación de la Cadera/fisiopatología , Luxación de la Cadera/terapia , Humanos , Lactante , Masculino , Enfermedades Musculoesqueléticas/fisiopatología , Ortopedia/métodos , Osteogénesis Imperfecta/fisiopatología , Osteogénesis Imperfecta/terapia , Escoliosis/fisiopatología , Escoliosis/terapiaRESUMEN
We present a 9-year-old male child having history of fractures on trivial trauma with a family history of the same. He was treated for osteogenesis imperfecta (OI; zolendronate, calcium and vitamin D) and showed clinical improvement. On evaluating his bone health using dual energy X-ray absorptiometry and peripheral quantitative CT, we found that the child had bone density within the reference range but a smaller bone mass for his height, low muscle mass and thin bones with a lower strength strain index in comparison with healthy children. Our case suggests that treatment with bisphosphonates results in increase in bone density; however, bones remain thin and the lean body mass in these children may also be low. Controlled physical activity to improve muscle health and newer approaches to improve bone geometry would result in better bone health in children with OI.
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Absorciometría de Fotón , Densidad Ósea , Osteogénesis Imperfecta/diagnóstico por imagen , Osteogénesis Imperfecta/fisiopatología , Tomografía Computarizada por Rayos X , Conservadores de la Densidad Ósea/uso terapéutico , Calcio/uso terapéutico , Niño , Difosfonatos/uso terapéutico , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Humanos , Masculino , Osteogénesis Imperfecta/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodos , Vitamina D/uso terapéutico , Ácido Zoledrónico/uso terapéuticoRESUMEN
Objectives Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by recurrent fractures due to congenital bone fragility. The only bisphosphonate approved for OI in Japan is pamidronate (PAM). To investigate whether monthly intravenous alendronate (ALN) infusions can maintain bone strength in OI children following cyclical PAM treatment. Methods A prospective and non-inferiority study was conducted. Eight school-age OI patients aged 8.5±2.0 years who were treated with cyclical PAM for 6.0±2.3 years were enrolled and switched to monthly intravenous ALN (0.030 mg/kg/month). Changes in L1-4 bone mineral density (BMD) Z-scores, fracture rates, and bone turnover markers for 12 months were analyzed. Results Average BMD Z-scores were -3.0±1.9, -2.9±2.0, and -2.2±2.0 in 12 months before enrollment, at enrollment, and after 12 months of ALN treatment, respectively. BMD Z-scores increased significantly during treatment with both PAM and ALN (p=0.012), and the effect of ALN was not inferior to that of PAM (p=0.67). There was no change in fracture rates (p=0.86) and bone turnover markers during the 12 months before and after enrollment. Additionally, ALN showed no remarkable side effects. Conclusions Our results suggest that monthly intravenous ALN can maintain bone strength after primary usage of cyclical PAM. We concluded that monthly intravenous ALN as a maintenance treatment following cyclical PAM administration can be an option for OI children.
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Alendronato/administración & dosificación , Osteogénesis Imperfecta/tratamiento farmacológico , Pamidronato/administración & dosificación , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Niño , Preescolar , Esquema de Medicación , Quimioterapia Combinada , Estudios de Equivalencia como Asunto , Femenino , Humanos , Lactante , Recién Nacido , Infusiones Intravenosas , Japón , Quimioterapia de Mantención/métodos , Masculino , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of collagen-related disorders characterized by osteopenia, bone fractures, spine deformities, and nonskeletal complications. Cardiopulmonary complications are the major cause of morbidity and mortality in adults with OI. The cause of such problems was often attributed solely to the presence of large scoliosis curves affecting pulmonary function and, indirectly, cardiovascular health. However, recent studies suggest this may not be the case. Therefore, determining the relationships and causative agents of cardiopulmonary problems in patients with OI, specifically pulmonary impairment, is important to improving the overall wellbeing, quality of life, and survival of these patients. QUESTIONS/PURPOSES: (1) Is cardiopulmonary fitness in OI solely related to the presence of scoliosis? (2) What is the prevalence of heart and lung complications in this adult population? (3) Does the presence of pulmonary impairment impact quality of life in adults with OI? METHODS: This is a prospective observational cross-sectional study. Within 1 year, each participant (n = 30) completed pulmonary function testing, echocardiogram, ECG, chest CT, AP spine radiography, and quality-of-life assessments (SF-36, St. George's Respiratory Questionnaire, Functional Outcomes of Sleep Questionnaire, and Pittsburgh Sleep Quality Index). In terms of pulmonary function, we differentiated restrictive and obstructive physiology using the ratio of forced expiratory volume over one second to forced vital capacity (FEV1/FVC), with restrictive lung physiology defined as FEV1/FVC > 0.8 and obstructive lung physiology as FEV1/FVC < 0.7. Spine radiographs were evaluated for scoliosis. Chest CT images were reviewed to qualitatively assess the lungs. The statistical analysis involved a Kruskall-Wallis test with Bonferroni's correction and a bivariate correlation analysis using Spearman's rho correlation coefficient (p < 0.05). RESULTS: Sixteen of 23 participants with restrictive lung physiology had scoliosis; their ages ranged from 19 years to 67 years. There was no correlation between the magnitude of the scoliosis curve and deficient pulmonary function (R = 0.08; p = 0.68). Seven participants had normal pulmonary function. The average scoliosis curve was 44 ± 29°. Thirteen participants had abnormal ECG findings while 10 had abnormal echocardiogram results. All but two individuals with abnormal chest CT results were found to have bronchial wall thickening. There were no differences in pulmonary or cardiac findings between OI types, except for FVC and total lung capacity, which were lower in individuals with Type III OI than in those with other types of OI. FEV1/FVC correlated with St. George's Respiratory Questionnaire (R = 0.429; p = 0.02) but not with Functional Outcomes of Sleep Questionnaire (R = -0.26; p = 0.19) or SF-36 scores (physical component summary: R = -0.037, p = 0.85; mental component summary: R = -0.204, p = 0.29). CONCLUSIONS: The lack of a relationship between decreased pulmonary function and the severity of scoliosis suggests that restrictive lung physiology in this population is likely because of factors intrinsic to OI and not entirely because of thoracic cage deformities. The fact that pulmonary impairment influences self-perceived quality of life exemplifies how detrimental such complications may be to everyday functioning. This also reinforces the importance of determining the underlying cause of cardiopulmonary impairment in this population to set clear clinical guidelines of care. LEVEL OF EVIDENCE: Level II, prognostic study.
Asunto(s)
Capacidad Cardiovascular , Cardiopatías/fisiopatología , Corazón/fisiopatología , Enfermedades Pulmonares/fisiopatología , Pulmón/fisiopatología , Osteogénesis Imperfecta/fisiopatología , Escoliosis/fisiopatología , Adulto , Anciano , Estudios Transversales , Femenino , Volumen Espiratorio Forzado , Estado de Salud , Corazón/diagnóstico por imagen , Cardiopatías/diagnóstico , Cardiopatías/epidemiología , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/epidemiología , Prevalencia , Estudios Prospectivos , Calidad de Vida , Medición de Riesgo , Factores de Riesgo , Escoliosis/diagnóstico , Escoliosis/epidemiología , Capacidad Vital , Adulto JovenRESUMEN
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