-
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 -
International Journal of Molecular... May 2023Vitamin D affects several body functions, and thus general health, due to its pleiotropic activity. It plays a key role in bone metabolism, and its deficiency impacts... (Review)
Review
Vitamin D affects several body functions, and thus general health, due to its pleiotropic activity. It plays a key role in bone metabolism, and its deficiency impacts bone development, leading to bone fragility. In osteogenesis imperfecta (OI), a group of hereditary connective tissue disorders characterized by bone fragility, additional factors, such as vitamin D deficiency, can affect the expression of the phenotype and aggravate the disorder. The aim of this scoping review was to assess the incidence of vitamin D deficit in OI patients and the association between vitamin D status and supplementation in individuals affected by OI. We searched the PubMed Central and Embase databases and included studies published between January/2000 and October/2022 evaluating vitamin D measurement and status (normal, insufficiency, deficiency) and supplementation for OI. A total of 263 articles were identified, of which 45 were screened by title and abstract, and 10 were included after a full-text review. The review showed that low levels of vitamin D was a frequent finding in OI patients. Vitamin D supplementation was mainly indicated along with drug therapy and calcium intake. Even if widely used in clinical practice, vitamin D supplementation for OI individuals still needs a better characterization and harmonized frame for its use in the clinical setting, as well as further studies focusing on its effect on bone fragility.
Topics: Humans; Vitamin D; Osteogenesis Imperfecta; Vitamins; Vitamin D Deficiency; Phenotype
PubMed: 37298368
DOI: 10.3390/ijms24119416 -
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 -
Bone Sep 2021Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and craniofacial and dental abnormalities such as congenitally missing teeth and teeth...
INTRODUCTION
Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and craniofacial and dental abnormalities such as congenitally missing teeth and teeth that failed to erupt which are believed to be doubled in OI patients than normal populations and were associated with low oral health quality of life. However, the etiology of these abnormalities remains unclear. To understand the factors influencing missing and unerupted teeth, we investigated their prevalence in a cohort of OI patients as a function of the clinical phenotype (OI type), the genetic variant type, the tooth type and the onset of bisphosphonate treatment.
METHOD
A total of 144 OI patients were recruited from The Shriners Hospital, Montreal, Canada, between 2016 and 2017. Patients were evaluated using intraoral photographs and panoramic radiographs. Missing teeth were evaluated in all patients, and unerupted teeth were assessed only in patients ≥15 years old (n = 82).
RESULTS
On average, each OI patient had 2.4 missing teeth and 0.8 unerupted teeth, and the most common missing and unerupted teeth were the premolars and the upper second molars, respectively. These phenomena were more prominent in OI type III and IV than in OI type I, and were not sex or age-related. Missing teeth were significantly more common in patients with C-propeptide variants than all other variants (p-value <0.05). Unerupted teeth were significantly more common in patients with α1 and α2 glycine variants or substitutions than in those with haploinsufficiency variants. Early-onset of bisphosphonate treatment would significantly increase the risk of unerupted teeth in patients with OI types III and IV (OR = 1.68, 95% CI (1.15-1.53)).
CONCLUSION
The prevalence of missing and unerupted teeth at the tooth type level in OI patients varies according to the nature of the collagen variants and the OI type. These findings highlight the role of collagen in tooth development and eruption.
Topics: Adolescent; Canada; Humans; Osteogenesis Imperfecta; Phenotype; Quality of Life; Tooth, Unerupted
PubMed: 34020077
DOI: 10.1016/j.bone.2021.116011 -
The Orthopedic Clinics of North America Apr 2019Osteogenesis imperfecta is a genetically and phenotypically heterogeneous disorder related to a defect or deficiency in the production of type I collagen. It is... (Review)
Review
Osteogenesis imperfecta is a genetically and phenotypically heterogeneous disorder related to a defect or deficiency in the production of type I collagen. It is characterized by brittle bones, fractures, spine and extremity deformity, and a host of extraskeletal manifestations. Type I collagen is present in bone, tendons, ligaments, skin, dentin, and the sclera of the eye and other connective tissues. Osteogenesis imperfecta includes a multitude of disease manifestations that may be present at birth or develop over time and vary depending on the severity of the disease. This article describes the disease presentation and management considerations from a pediatric orthopedic perspective.
Topics: Adolescent; Bone Diseases, Developmental; Calcium; Child; Child, Preschool; Diphosphonates; Exercise; Female; Foot Orthoses; Fractures, Bone; Humans; Infant; Interdisciplinary Communication; Limb Deformities, Congenital; Male; Osteogenesis Imperfecta; Scoliosis; Spine; Vitamin D
PubMed: 30850078
DOI: 10.1016/j.ocl.2018.10.003 -
Wiener Medizinische Wochenschrift (1946) Jul 2015Osteogenesis imperfecta (OI) is an extremely heterogeneous group of heritable connective tissue disorders. Most of the affected patients carry autosomal dominant... (Review)
Review
Osteogenesis imperfecta (OI) is an extremely heterogeneous group of heritable connective tissue disorders. Most of the affected patients carry autosomal dominant mutations in the genes encoding for collagen type I, the most abundant protein of the bone extracellular matrix. The resulting phenotypes are extremely broad and have been classified by Sillence and colleagues into four groups according to clinical, radiological and genetic criteria.More recently, proteins have been described that interact directly or indirectly with collagen biosynthesis and their deficiency result in rare forms of mostly autosomal recessive OI sharing phenotypic features of 'classical' types but lacking primary defects in type I collagen. Consequently the Sillence classification has been gradually expanded to include novel forms based on the underlying mutations. The goal of this article is to revisit the actual OI classification and to outline current approaches in categorizing the disorder.
Topics: Chromosome Aberrations; Collagen Type I; Collagen Type I, alpha 1 Chain; DNA Mutational Analysis; Genes, Dominant; Genes, Recessive; Humans; Osteogenesis Imperfecta; Phenotype; Protein Processing, Post-Translational
PubMed: 26208476
DOI: 10.1007/s10354-015-0368-3 -
Current Osteoporosis Reports Feb 2016Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount,... (Review)
Review
Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.
Topics: Bone Density Conservation Agents; Calcium; Diphosphonates; Fractures, Spontaneous; Humans; Occupational Therapy; Osteogenesis Imperfecta; Physical Therapy Modalities; Resistance Training; Vitamin D
PubMed: 26861807
DOI: 10.1007/s11914-016-0299-y -
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 -
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 -
International Journal of Pediatric... Nov 2021Osteogenesis Imperfecta is a genetic disorder affecting the synthesis of collagen in the body. It is also known as 'Brittle Bone Disease'. It is heterogenous in its...
BACKGROUND
Osteogenesis Imperfecta is a genetic disorder affecting the synthesis of collagen in the body. It is also known as 'Brittle Bone Disease'. It is heterogenous in its clinical presentation. The commonest presentation is a history of frequent fractures, joint deformities and blue sclera. Secondary deformities of the extremities, spine, skull as well short stature observed frequently. Hearing loss has been well documented to occur in Osteogenesis Imperfecta. It is most commonly seen in types I, II and III. Hearing loss forms part of the diagnostic criteria for these types. Depending on the study, the prevalence of hearing loss in children with Osteogenesis imperfecta is between 6.7% and 77.3% The estimated prevalence of Osteogenesis Imperfecta is 1 in 20000.
OBJECTIVES
In South Africa, the commonest type of Osteogenesis Imperfecta was found to be Type III. The prevalence of OI Type III has been estimated to be between 1:125000 and 1:200000. Hearing loss is a common feature of OI Type III.
METHODS
This study was a Prospective Cross-sectional study. Ethics Approval was obtained from the University of Witwatersrand Ethics committee (Ethics number M190975) Children with Osteogenesis Imperfecta attending the Metabolic Bone Clinic at Chris Hani Baragwanath Academic Hospital were the target group. The patients and their parents or guardians were recruited at the clinic after a consent and or an assent was obtained. An Otoscopy followed by tympanometry and a hearing screen based on the age of the patient was done. DPEOAEs were also done as a screening test to confirm the pure tone audiogram findings. The results were given to the patients and their parents/guardians immediately.
RESULTS
The paediatric patients with Osteogenesis Imperfecta who consented to take part in the study had their hearing screen done at the Audiology Department at Chris Hani Baragwanath Academic Hospital. All of the children were found to have normal hearing. On tympanometry, all except 2 were found to have type A curves in bilaterally. Two patients had a type As curve in one ear with an A curve on the other side.
CONCLUSION
Hearing loss in Osteogenesis Imperfecta forms part of the diagnostic criteria for certain types of this genetic disorder. Hearing loss in the paediatric patients does not seem to be as prevalent as previously thought. All the patients involved in the study were receiving the bisphosphonate therapy (Zoledronic acid) for OI. This may possibly cause a delay in the onset of hearing loss but long term follow-up studies and bigger sample sizes will be required to prove this hypothesis.
Topics: Child; Cross-Sectional Studies; Deafness; Hearing Loss; Humans; Osteogenesis Imperfecta; Prospective Studies
PubMed: 34500359
DOI: 10.1016/j.ijporl.2021.110914