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Current Osteoporosis Reports Dec 2023This review aims to provide a review of the multidisciplinary management of infants with osteogenesis imperfecta (OI) during the first year of life, focusing on those... (Review)
Review
PURPOSE OF REVIEW
This review aims to provide a review of the multidisciplinary management of infants with osteogenesis imperfecta (OI) during the first year of life, focusing on those with severe disease. The authors draw on published literature and direct experience of working in a large paediatric centre specialising in the management of rare bone disease.
RECENT FINDINGS
Whilst understanding of the pathophysiology of OI has grown over the past decade, the evidence base for management of infants remains limited. There has been a greater recognition of certain subjects of concern including pain management, cervical spine deformity, and neurocognitive development. Both international consensus guidelines on rehabilitation and disease-specific growth charts have been welcomed by clinical teams. The early involvement of multidisciplinary specialist care is critical in ensuring optimal care for the infant with severe OI. A long-term perspective which focuses on the axial, craniofacial, and peripheral skeleton as well as on development more generally provides a framework which can guide the management of infants with severe OI.
Topics: Child; Infant; Humans; Osteogenesis Imperfecta; Diphosphonates; Bone and Bones
PubMed: 37752354
DOI: 10.1007/s11914-023-00823-5 -
European Annals of Otorhinolaryngology,... Oct 2019The goal is to clarify the epidemiology of hearing loss in patients with osteogenesis imperfecta (OI), so as to improve management. A literature review analyzed data... (Review)
Review
The goal is to clarify the epidemiology of hearing loss in patients with osteogenesis imperfecta (OI), so as to improve management. A literature review analyzed data from 15 patient series. Hearing loss prevalence in OI varied widely, from 2% to 94.1%. Typically, hearing loss was conductive in young patients and sensorineural in older patients. Prevalence increased with age, but after 50 years the increase was slight, and seldom became total. Hearing loss was usually bilateral, but not necessarily symmetrical. There were no correlations between type of mutation (COL1A1 or COL1A2), prevalence, type or severity of hearing loss, or age of symptom onset; there was intra-familial variability. There was also no correlation between mutated gene, type of mutation and auditory phenotype. Frequency, type and severity of hearing loss were unrelated to other clinical parameters. Hearing loss prevalence depended on type of OI: higher in type I and lower in type IV. Incidence of otitis media was higher in children with OI, related to the associated craniofacial dysmorphia. Hearing screening before 5 years of age with long-term follow-up are recommended.
Topics: Aging; Bone Demineralization, Pathologic; Hearing Loss, Conductive; Hearing Loss, Sensorineural; Humans; Osteogenesis Imperfecta; Temporal Bone
PubMed: 31202667
DOI: 10.1016/j.anorl.2019.05.004 -
Journal of Musculoskeletal & Neuronal... Jun 2017Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI.... (Review)
Review
Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI. Muscle mass is decreased in OI, even when short stature is taken into account. Dynamic muscle tests aiming at maximal eccentric force production reveal functional deficits that can not be explained by low muscle mass alone. However, it appears that diaphyseal bone mass is normally adapted to muscle force. At present the determinants of muscle mass and function in OI have not been clearly defined. Physiotherapy interventions and bisphosphonate treatment appear to have some effect on muscle function in OI. Interventions targeting muscle mass have shown encouraging results in OI animal models and are an interesting area for further research.
Topics: Animals; Humans; Muscle, Skeletal; Muscular Diseases; Osteogenesis Imperfecta
PubMed: 28574406
DOI: No ID Found -
The FEBS Journal Aug 2019The limited accessibility of bone and its mineralized nature have restricted deep investigation of its biology. Recent breakthroughs in identification of mutant proteins... (Review)
Review
The limited accessibility of bone and its mineralized nature have restricted deep investigation of its biology. Recent breakthroughs in identification of mutant proteins affecting bone tissue homeostasis in rare skeletal diseases have revealed novel pathways involved in skeletal development and maintenance. The characterization of new dominant, recessive and X-linked forms of the rare brittle bone disease osteogenesis imperfecta (OI) and other OI-related bone fragility disorders was a key player in this advance. The development of in vitro models for these diseases along with the generation and characterization of murine and zebrafish models contributed to dissecting previously unknown pathways. Here, we describe the most recent advances in the understanding of processes involved in abnormal bone mineralization, collagen processing and osteoblast function, as illustrated by the characterization of new causative genes for OI and OI-related fragility syndromes. The coordinated role of the integral membrane protein BRIL and of the secreted protein PEDF in modulating bone mineralization as well as the function and cross-talk of the collagen-specific chaperones HSP47 and FKBP65 in collagen processing and secretion are discussed. We address the significance of WNT ligand, the importance of maintaining endoplasmic reticulum membrane potential and of regulating intramembrane proteolysis in osteoblast homeostasis. Moreover, we also examine the relevance of the cytoskeletal protein plastin-3 and of the nucleotidyltransferase FAM46A. Thanks to these advances, new targets for the development of novel therapies for currently incurable rare bone diseases have been and, likely, will be identified, supporting the important role of basic science for translational approaches.
Topics: Animals; Bone Diseases, Metabolic; Calcification, Physiologic; Humans; Mutation; Osteoblasts; Osteogenesis Imperfecta
PubMed: 31220415
DOI: 10.1111/febs.14963 -
European Journal of Medical Genetics Apr 2024Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone...
Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may be confirmed by genetic testing. However, imaging remains pivotal in the evaluation of this disease. The aim of this article is to review the current role played by the various radiologic techniques in the diagnosis and monitoring of OI in the postnatal setting as well as to discuss recent advances and future perspectives in OI imaging. Conventional Radiography and Dual-energy X-ray Absorptiometry (DXA) are currently the two most used imaging modalities in OI. The cardinal radiographic features of OI include generalized osteopenia/osteoporosis, bone deformities, and fractures. DXA is currently the most available technique to assess Bone Mineral Density (BMD), specifically areal BMD (aBMD). However, DXA has important limitations and cannot fully characterize bone fragility in OI based on aBMD. Novel DXA-derived parameters, such as Trabecular Bone Score (TBS), may provide further insight into skeletal changes induced by OI, but evidence is still limited. Techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can be useful as problem-solvers or in specific settings, including the evaluation of cranio-cervical abnormalities. Recent evidence supports the use of High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) as a promising tool to improve the characterization of bone fragility in OI. However, HR-pQCT remains a primarily research technique at present. Quantitative Computed Tomography (QCT) is an alternative to DXA for the determination of BMD at central sites, with distinct advantages but considerably higher radiation exposure. Quantitative Ultrasound (QUS) is a portable, inexpensive, and radiation-free modality that may complement DXA evaluation, providing information on bone quality. However, evidence of usefulness of QUS in OI is poor. Radiofrequency Echographic Multi Spectrometry (REMS) is an emerging non-ionizing imaging method that holds promise for the diagnosis of low BMD and for the prediction of fracture risk, but so far only one published study has investigated its role in OI. To conclude, several different radiologic techniques have proven to be effective in the diagnosis and monitoring of OI, each with their own specificities and peculiarities. Clinicians should be aware of the strategic role of the various modalities in the different phases of the patient care process. In this scenario, the development of international guidelines including recommendations on the role of imaging in the diagnosis and monitoring of OI, accompanied by continuous active research in the field, could significantly improve the standardization of patient care.
Topics: Humans; Osteogenesis Imperfecta; Bone Density; Osteoporosis; Absorptiometry, Photon; Fractures, Bone
PubMed: 38369057
DOI: 10.1016/j.ejmg.2024.104926 -
Jornal de Pediatria 2014Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. (Review)
Review
OBJECTIVE
Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification.
SOURCES
Literature review in the PubMed and OMIM databases, followed by selection of relevant references.
SUMMARY OF THE FINDINGS
In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented.
CONCLUSIONS
Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference.
Topics: Collagen Type I; Humans; Mutation; Osteogenesis Imperfecta
PubMed: 25046257
DOI: 10.1016/j.jped.2014.05.003 -
Journal of Bone and Mineral Research :... Apr 2016Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between... (Review)
Review
Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density-the quantity of mineral in relation to the quantity of matrix within a specific bone volume-and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment-largely improved architecture and possibly some macroscale toughening-and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales.
Topics: Bone Density; Fractures, Bone; Humans; Osteogenesis Imperfecta
PubMed: 26987995
DOI: 10.1002/jbmr.2835 -
Frontiers in Endocrinology 2022Osteogenesis Imperfecta (OI) is a complex disease caused by genetic alterations in production of collagen type I, and collagen-related proteins. Bone fragility is the...
Osteogenesis Imperfecta (OI) is a complex disease caused by genetic alterations in production of collagen type I, and collagen-related proteins. Bone fragility is the most common patient issue, but extraskeletal complications also present an adverse factor in the quality of life and prognosis of patients with OI. However, still little is known about the morbidity and mortality of these patients. The objective of this paper is to determine and describe to what extent OI impacts patients' life in terms of hospitalization and complications describing the incidence and prevalence of the Dutch cohort of OI patients and the characteristics of their hospital admissions. Information regarding OI patients and their hospital admission was extracted from the Statistics Netherlands Database and matched to the OI Genetics Database of Amsterdam UMC. Hospital admission data was available for 674 OI patients. This OI nationwide registry study shows that the life expectancy of OI patients is adversely affected by the disease. The median annual incidence risk of OI between 1992 and 2019 was 6.5 per 100,000 live births. Furthermore, patients with OI had a 2.9 times higher hospitalization rate compared to the general Dutch population. The highest hospitalization rate ratio of 8.4 was reported in the patient group between 0 and 19 years old. OI type and severity had impact on extraskeletal manifestations, which play a key role in the numerous hospital admissions. More awareness about the impact of OI on patients' life is needed to improve and implement prevention and follow-up guidelines.
Topics: Adolescent; Adult; Child; Child, Preschool; Hospitalization; Hospitals; Humans; Infant; Infant, Newborn; Netherlands; Osteogenesis Imperfecta; Prevalence; Quality of Life; Registries; Young Adult
PubMed: 35546999
DOI: 10.3389/fendo.2022.869604 -
Acta Medica Academica Aug 2021The aim of this paper is to describe the varying clinical and imaging manifestations of Osteogenesis Imperfecta (OI) in the fetus, the child, and the adult. OI is a...
The aim of this paper is to describe the varying clinical and imaging manifestations of Osteogenesis Imperfecta (OI) in the fetus, the child, and the adult. OI is a genetic disorder with mutation of Type 1 and non-type 1 collagen genes that results in disruption of multiple collagen based organ systems, most notably bones, often leading to "brittle bones". Additional features such as blue sclera, dentinogenesis imperfecta, joint and ligamentous hyperlaxity, hearing loss and cardiac defects may be present. Currently, there are at least 30 recognized genetic forms of OI. Given the multiple genes involved, variable genetic inheritance, and the wide range in phenotype, diagnosis can be challenging. While OI may sometimes be diagnosed in the fetus, patients with mild forms of OI may be diagnosed in childhood or even in adulthood. Imaging, including ultrasound, radiography, computed tomography, and magnetic resonance imaging, plays an important role in the diagnoses of OI in the fetus, the child, and the adult. Imaging is also crucial in identifying the many multisystem manifestations of OI. In particular, imaging can help differentiate manifestations of OI from injuries sustained in non-accidental trauma. Age, severity and manner of presentation of OI vary broadly depending on the specific genetic mutation involved, mode of inheritance, and age of the patient. Successful diagnosis of OI hinges on a detailed knowledge of the variable presentation and complications that may be encountered with this disease. CONCLUSION: In conclusion, OI comprises a heterogeneous group of genetic disorders responsible for bone fragility and additional connective tissue disorders, which can result in specific clinical and imaging findings in the fetus, the child, and the adult.
Topics: Adult; Fetus; Humans; Joint Instability; Mutation; Osteogenesis Imperfecta; Radiography
PubMed: 34847680
DOI: 10.5644/ama2006-124.343 -
The Journal of Clinical Endocrinology... Jan 2022Mutations in type I collagen or collagen-related proteins cause osteogenesis imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced... (Observational Study)
Observational Study
CONTEXT
Mutations in type I collagen or collagen-related proteins cause osteogenesis imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility or intrinsic defects in osteoblast differentiation increasing adipocyte development.
OBJECTIVE
This study compares adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences.
METHODS
We studied 90 participants, 30 with OI (11 COL1A1 Gly, 8 COL1A2 Gly, 4 COL1A1 non-Gly, 1 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy x-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates, to examine the relationship of OI genotypes and phenotypic Types.
RESULTS
FM% did not differ significantly in all patients with OI vs HC (OI: 36.6% ± 1.9%; HC: 32.7% ± 1.2%; P = 0.088). FM% was, however, greater than HC for those with non-COL variants (P = 0.016). FM% did not differ from HC among OI Types (P values > 0.05).Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5 ± 44.7 kcal/d; HC: 1377.0 ± 96 kcal/d; P = 0.345). However, those with non-COL variants (P = 0.016) and Type VI OI (P = 0.04) had significantly lower REE than HC.
CONCLUSION
Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.
Topics: Absorptiometry, Photon; Adiposity; Adolescent; Adult; Basal Metabolism; Body Mass Index; Case-Control Studies; Cell Differentiation; Child; Collagen; DNA Mutational Analysis; Female; Healthy Volunteers; Humans; Male; Middle Aged; Osteoblasts; Osteogenesis Imperfecta; Young Adult
PubMed: 34519823
DOI: 10.1210/clinem/dgab679