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Best Practice & Research. Clinical... Mar 2008Osteogenesis Imperfecta is a heritable disorder characterized by bone fragility and low bone mass, with a wide spectrum of clinical expression. This review gives an... (Review)
Review
Osteogenesis Imperfecta is a heritable disorder characterized by bone fragility and low bone mass, with a wide spectrum of clinical expression. This review gives an update on its classification, the recent developments in the understanding of its pathophysiological mechanisms, and the current status of bisphosphonate therapy. Other therapeutic approaches and future directions of research are briefly discussed.
Topics: Bone Density Conservation Agents; Diagnosis, Differential; Diphosphonates; Humans; Ilium; Osteogenesis Imperfecta; Pamidronate
PubMed: 18328983
DOI: 10.1016/j.berh.2007.12.012 -
Radiologic Technology 2008"Fragile bones" have been described in medical literature for centuries. Cases dating from antiquity include dental and skeletal details eerily similar to those found... (Review)
Review
"Fragile bones" have been described in medical literature for centuries. Cases dating from antiquity include dental and skeletal details eerily similar to those found among modern patients whose bones fracture easily and whose bodies show signs of muscular and other weakness. Osteogenesis imperfecta--whose name implies "imperfect birth of bone"--is one of these inherited fragile bone syndromes. A generalized disorder of the body's connective tissues, it is most obvious in its effect on bone, but also involves the body's ligaments, tendons, fascia, eyes, skin, teeth and ears. Radiographs, bone scans and other imaging tools are essential in the initial diagnosis, assessment of fracture risk, and planning and tracking of treatment.
Topics: Fractures, Spontaneous; Humans; Osteogenesis Imperfecta; Radiography
PubMed: 18650529
DOI: No ID Found -
The Journal of the American Academy of... 1998Osteogenesis imperfecta (OI) is a genetically determined disorder of connective tissue characterized by bone fragility. The disease state encompasses a phenotypically... (Review)
Review
Osteogenesis imperfecta (OI) is a genetically determined disorder of connective tissue characterized by bone fragility. The disease state encompasses a phenotypically and genotypically heterogeneous group of inherited disorders that result from mutations in the genes that code for type I collagen. The disorder is manifest in tissues in which the principal matrix protein is type I collagen (mainly bone, dentin, sclerae, and ligaments). Musculoskeletal manifestations are variable in severity along a continuum ranging from perinatal lethal forms with crumpled bones to moderate forms with deformity and propensity to fracture to clinically silent forms with subtle osteopenia and no deformity. The differential diagnosis includes other entities with multiple fractures, deformities, and osteopenia. Classification is based on the timing of fractures or on multiple clinical, genetic, and radiologic features. Molecular genetic studies have identified more than 150 mutations of the COL1A1 and COL1A2 genes, which encode for type I procollagen. Various systemic treatments have been attempted; however, these interventions have been ineffective or inconclusive or are still experimental. Gene therapy has the potential to increase the synthesis of type I collagen in mild variants and to correct mutations in severe variants, but there are a great number of technical difficulties to overcome. The goals of treatment of OI are to maximize function, minimize deformity and disability, maintain comfort, achieve relative independence in activities of daily living, and enhance social integration. Attainment of these goals requires a team approach to tailor treatment needs to the severity of the disease and the age of the patient. Nonoperative management is the mainstay of orthopaedic treatment, with the goals of preventing and treating fractures and enhancing locomotion. Operative intervention is indicated for recurrent fractures or deformity that impairs function.
Topics: Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 7; Collagen; Humans; Mutation; Osteogenesis Imperfecta
PubMed: 9682085
DOI: 10.5435/00124635-199807000-00004 -
Metabolism: Clinical and Experimental Mar 2018Osteogenesis imperfecta (OI) is the most common inherited form of bone fragility and includes a heterogenous group of genetic disorders which most commonly result from... (Review)
Review
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-β inhibition. Gene targeting approaches are under evaluation. More research is needed to delineate the best therapeutic approach in this heterogeneous disease.
Topics: Adult; Bone Density; Child; Humans; Osteogenesis Imperfecta
PubMed: 28625337
DOI: 10.1016/j.metabol.2017.06.001 -
Clinical Genetics Jan 2021Osteogenesis imperfecta (OI) is a relatively common genetic skeletal disorder with an estimated frequency of 1 in 20 000 worldwide. The manifestations are diverse and... (Review)
Review
Osteogenesis imperfecta (OI) is a relatively common genetic skeletal disorder with an estimated frequency of 1 in 20 000 worldwide. The manifestations are diverse and although individually rare, the several different forms contribute to the production of a significant number of affected individuals with considerable morbidity and mortality. During the last decade, there have been extensive molecular investigations into the etiology of OI and these advances have direct relevance to the medical management of the disorder, and the purpose of this review is to document the history and evolution of the nosology of OI. The current nosology, based on molecular concepts, which are crucial in the identification of genotype-phenotype correlations in persons with OI, is also outlined. The successive revisions of the nosology and classification of OI have highlighted the importance of the nomenclature of the condition in order for it to be recognized by clinicians, scientists and patient advocacy groups. In this way, improved counseling of patients and individualized, tailored therapeutic approaches based on the underlying pathophysiology of the individual's type of OI have been facilitated.
Topics: Bone and Bones; Genetic Association Studies; Humans; Osteogenesis Imperfecta; Phenotype
PubMed: 32901963
DOI: 10.1111/cge.13846 -
The Journal of Bone and Joint Surgery.... Mar 1997
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Delaware Medical Journal Jun 2016
Topics: Humans; Osteogenesis Imperfecta
PubMed: 27506061
DOI: No ID Found -
Current Opinion in Pediatrics Feb 1997In the past 20 years, tremendous strides have been made in our understanding of the biochemical and genetic abnormalities associated with osteogenesis imperfecta (OI).... (Review)
Review
In the past 20 years, tremendous strides have been made in our understanding of the biochemical and genetic abnormalities associated with osteogenesis imperfecta (OI). Prenatal diagnostic techniques have allowed early detection of this disorder, particularly in families in which the actual molecular defect is already known. Although medical and surgical management of patients with OI continue to improve, the proper management of such problems as basilar impression still need to be determined. Progress in the treatment of OI at a molecular level is encouraging.
Topics: Bone Density; Child; Child Abuse; Diagnosis, Differential; Genetic Counseling; Humans; Molecular Biology; Osteogenesis Imperfecta; Prenatal Diagnosis
PubMed: 9088762
DOI: 10.1097/00008480-199702000-00019 -
Bailliere's Clinical Endocrinology and... Feb 1988Major advances have occurred in the classification of OI and in the definition of underlying molecular defects. A clearer understanding of the pathogenesis of OI and of... (Review)
Review
Major advances have occurred in the classification of OI and in the definition of underlying molecular defects. A clearer understanding of the pathogenesis of OI and of the relationships between the phenotypes and genotypes should emerge. The study of induced mutations in selected regions of the collagen genes with expression in cultured cells or transgenic mice should hasten this process. These advances will also provide a basis for studies into the large number of other genetically determined connective tissue disorders that are grouped together as the skeletal dysplasias. The results of recent studies in OI are providing a unique insight into many aspects of collagen and connective tissue biochemistry, physiology and pathology.
Topics: Adolescent; Adult; Animals; Cells, Cultured; Child; Collagen; Disease Models, Animal; Humans; Infant; Infant, Newborn; Osteogenesis Imperfecta; Prenatal Diagnosis
PubMed: 3044330
DOI: 10.1016/s0950-351x(88)80014-4 -
Clinics in Orthopedic Surgery Dec 2020Osteogenesis imperfecta (OI) is characterized by recurring fractures and limb and spine deformities. With the advent of medical therapeutics and the discovery of... (Review)
Review
Osteogenesis imperfecta (OI) is characterized by recurring fractures and limb and spine deformities. With the advent of medical therapeutics and the discovery of causative genes, as well as the introduction of a newly devised intramedullary rod, the general condition and ambulatory function of patients diagnosed with OI have been improved over the past decades. This review covers recent developments in research and management of OI.
Topics: Humans; Osteogenesis Imperfecta
PubMed: 33274017
DOI: 10.4055/cios20060