scholarly journals Complex spine deformities in young patients with severe osteogenesis imperfecta: current concepts review

2019 ◽  
Vol 13 (1) ◽  
pp. 22-32 ◽  
Author(s):  
R. M. Castelein ◽  
C. Hasler ◽  
I. Helenius ◽  
D. Ovadia ◽  
M. Yazici ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Young Patients ◽  
Surgical Care ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Type I ◽  
Vertebral Deformities ◽  
Spine Deformities ◽  
Paediatric Orthopaedic ◽  
Chest Deformities

The severity of osteogenesis imperfecta (OI), the associated reduced quality and quantity of collagen type I, the degree of bone fragility, ligamentous laxity, vertebral fractures and multilevel vertebral deformities all impair the mechanical integrity of the whole spinal architecture and relate to the high prevalence of progressive kyphoscoliotic deformities during growth. Bisphosphonate therapy may at best slow down curve progression but does not seem to lower the prevalence of deformities or the incidence of surgery. Brace treatment is problematic due to pre-existing chest wall deformities, stiffness of the curve and the brittleness of the ribs which limit transfer of corrective forces from the brace shell to the spine. Progressive curves entail loss of balance, chest deformities, pain and compromise of pulmonary function and eventually require surgical stabilization, usually around puberty. Severe vertebral deformities including deformed, small pedicles, highly brittle bones and chest deformities, short deformed trunks and associated issues like C-spine and cranial base abnormalities (basilar impressions, cervical kyphosis) as well as deformed lower and upper extremities are posing multiple peri- and intraoperative challenges. Hence, an early multidisciplinary approach (anaesthetist, pulmonologist, paediatric orthopaedic spine surgeon) is mandatory.This paper was written under the guidance of the Spine Study Group of the European Paediatric Orthopaedic Society. It highlights the most pertinent information given in the current literature and various practical aspects on surgical care of spine deformities in young OI patients based on the personal experience of the contributing authors.

scholarly journals Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children

2021 ◽  
Vol 9 (5) ◽  
pp. 49
Author(s):  
Huong Thi Thu Nguyen ◽  
Dung Chi Vu ◽  
Duc Minh Nguyen ◽  
Quang Dinh Dang ◽  
Van Khanh Tran ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Disorder ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Open Bite ◽  
Type I ◽  
Dentinogenesis Imperfecta ◽  
Type Iv ◽  
Brown Discoloration ◽  
Study Participants

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass, caused mainly by mutations in collagen type I encoding genes. The current study aimed to evaluate dentinogenesis imperfecta (DI), oral manifestations and caries status of OI children. Sixty-eight children (41 males, 27 females) aged from 3 to 17 years old (mean 9 ± 4.13) participated in the study. Participants were classified into three OI type groups (I—2 cases, III—31 cases and IV—35 cases). Clinical examination and an orthopantomogram were used to obtain prevalences and associations of DI, caries status, malocclusion, crossbite, open bite, eruption, impaction and missing teeth with OI. The prevalence of DI among OI patients was 47.1%, more common in OI type III than type IV. The yellow-brown discoloration type was more vulnerable to attrition than the opalescent-grey one in the primary dentition. OI seemed not to have a high risk of caries; the prevalence of caries was 69.1%. A high incidence of malocclusion, crossbite and open bite was observed. In-depth oral information would provide valuable data for better dental management in OI patients. Parents and general doctors should pay more attention to dental care to prevent caries and premature tooth loss.

scholarly journals Calvaria Bone Transcriptome in Mouse Models of Osteogenesis Imperfecta

2021 ◽  
Vol 22 (10) ◽  
pp. 5290
Author(s):  
Pierre Moffatt ◽  
Iris Boraschi-Diaz ◽  
Juliana Marulanda ◽  
Ghalib Bardai ◽  
Frank Rauch
Keyword(s):  
Osteogenesis Imperfecta ◽  
Mouse Models ◽  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Type I ◽  
Growth Factor Beta ◽  
Upregulated Genes

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.

scholarly journals Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
I. Mouna Ben Amor ◽  
Francis H. Glorieux ◽  
Frank Rauch
Keyword(s):  
Osteogenesis Imperfecta ◽  
Autosomal Dominant ◽  
Collagen Type ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Clinical Severity ◽  
Type I ◽  
Review Of The Literature ◽  
Single Centre ◽  
Wide Range

Osteogenesis imperfecta, discussed in Baldridge et al. 2008 is an inherited bone fragility disorder with a wide range of clinical severity that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I alpha chains. Here we describe genotype-phenotype correlations in OI patients who have mutations affecting collagen type I. This paper is based on findings in a large single-centre OI population and a review of the literature.

scholarly journals Metabolic phenotype in the mouse model of osteogenesis imperfecta

2017 ◽  
Vol 234 (3) ◽  
pp. 279-289 ◽  
Author(s):  
Iris Boraschi-Diaz ◽  
Josephine T Tauer ◽  
Omar El-Rifai ◽  
Delphine Guillemette ◽  
Geneviève Lefebvre ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Type I ◽  
Undercarboxylated Osteocalcin ◽  
Activity Levels ◽  
Body Energy ◽  
Circulating Levels

Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2. Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O2 consumption and CO2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin.

scholarly journals Collagen transport and related pathways in Osteogenesis Imperfecta

2021 ◽  
Author(s):  
Lauria Claeys ◽  
Silvia Storoni ◽  
Marelise Eekhoff ◽  
Mariet Elting ◽  
Lisanne Wisse ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Posttranslational Modifications ◽  
Collagen Type ◽  
Retrograde Transport ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Disease Classification ◽  
Type I ◽  
Complex Process ◽  
Molecular Landscape

AbstractOsteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classification and disease course prediction. Although collagen type I defects are long established as the primary cause of the bone pathology, we are still far from comprehending the complete mechanism. In the last years, the advent of next generation sequencing has triggered the discovery of many new genetic causes for OI, helping to draw its molecular landscape. It has become clear that, in addition to collagen type I genes, OI can be caused by multiple proteins connected to different parts of collagen biosynthesis. The production of collagen entails a complex process, starting from the production of the collagen Iα1 and collagen Iα2 chains in the endoplasmic reticulum, during and after which procollagen is subjected to a plethora of posttranslational modifications by chaperones. After reaching the Golgi organelle, procollagen is destined to the extracellular matrix where it forms collagen fibrils. Recently discovered mutations in components of the retrograde transport of chaperones highlight its emerging role as critical contributor of OI development. This review offers an overview of collagen regulation in the context of recent gene discoveries, emphasizing the significance of transport disruptions in the OI mechanism. We aim to motivate exploration of skeletal fragility in OI from the perspective of these pathways to identify regulatory points which can hint to therapeutic targets.

scholarly journals Osteogénesis imperfecta (OI) en una mujer adulta y su hija: reporte de caso

2017 ◽  
Vol 3 (3) ◽  
pp. 37-40
Author(s):  
Juan Camilo Sarmiento Ramón ◽  
Juan Carlos Rojas Castillo ◽  
Edwin Antonio Wandurraga Sánchez ◽  
Gustavo Adolfo Parra Serrano ◽  
Juan Guillermo Sarmiento Ramón
Keyword(s):  
Connective Tissue ◽  
Osteogenesis Imperfecta ◽  
Autosomal Dominant ◽  
Collagen Type ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Type I ◽  
History Of ◽  
The Moment ◽  
Common Manifestation

La osteogénesis imperfecta (OI) corresponde a un conjunto de trastornos hereditarios del tejido conectivo que tienen como manifestación común la fragilidad ósea. Su etiología es de origen genético y la gran mayoría de casos corresponden a mutaciones autosómicas dominantes de genes que codifican para el colágeno tipo I. Su diagnóstico es primariamente clínico basado en las características típicas de la enfermedad. Reportamos el caso de una mujer con historia de fracturas recurrentes en diferentes ocasiones, y el de su hija de tres años, quien al momento del reporte ya ha presentado dos fracturas.AbstractOsteogenesis imperfecta (OI) encompasses a group of inherited connective tissue with bone fragility as its common manifestation. Its etiology is genetic in nature and the vast majority of cases are due to autosomal dominant mutations of genes that code for collagen type I proteins. Diagnosis is primarily based on the typical clinical features of the disease. We report the case of a woman with a history of recurrent fractures at different moments in time, and her three year old daughter who at the moment of this report has already had two fractures.

scholarly journals Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta

2021 ◽  
Vol 10 (14) ◽  
pp. 3141
Author(s):  
Hyerin Jung ◽  
Yeri Alice Rim ◽  
Narae Park ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Disease Modeling ◽  
Bone Fragility ◽  
Osteogenic Potential ◽  
Type I ◽  
Gene Correction ◽  
Col1a1 Gene ◽  
Collagen Formation

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of COL1A1 or COL1A2. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the COL1A1 gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the COL1A1 gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9.

scholarly journals Early-Onset Osteoporosis

2021 ◽  
Author(s):  
Outi Mäkitie ◽  
M. Carola Zillikens
Keyword(s):  
Young Adults ◽  
Early Onset ◽  
Type I Collagen ◽  
Young Patients ◽  
Fragility Fractures ◽  
Underlying Disease ◽  
Bone Fragility ◽  
Sphingolipid Metabolism ◽  
Type I ◽  
Loss Of Function

AbstractOsteoporosis is a skeletal disorder with enhanced bone fragility, usually affecting the elderly. It is very rare in children and young adults and the definition is not only based on a low BMD (a Z-score < − 2.0 in growing children and a Z-score ≤ − 2.0 or a T-score ≤ − 2.5 in young adults) but also on the occurrence of fragility fractures and/or the existence of underlying chronic diseases or secondary factors such as use of glucocorticoids. In the absence of a known chronic disease, fragility fractures and low BMD should prompt extensive screening for secondary causes, which can be found in up to 90% of cases. When fragility fractures occur in childhood or young adulthood without an evident secondary cause, investigations should explore the possibility of an underlying monogenetic bone disease, where bone fragility is caused by a single variant in a gene that has a major role in the skeleton. Several monogenic forms relate to type I collagen, but other forms also exist. Loss-of-function variants in LRP5 and WNT1 may lead to early-onset osteoporosis. The X-chromosomal osteoporosis caused by PLS3 gene mutations affects especially males. Another recently discovered form relates to disturbed sphingolipid metabolism due to SGMS2 mutations, underscoring the complexity of molecular pathology in monogenic early-onset osteoporosis. Management of young patients consists of treatment of secondary factors, optimizing lifestyle factors including calcium and vitamin D and physical exercise. Treatment with bone-active medication should be discussed on a personalized basis, considering the severity of osteoporosis and underlying disease versus the absence of evidence on anti-fracture efficacy and potential harmful effects in pregnancy.

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