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European Cells & Materials Jun 2003Osteogenesis imperfecta is a heritable disorder of bone formation resulting in low bone mass and a propensity to fracture. It exhibits a broad range of clinical... (Review)
Review
Osteogenesis imperfecta is a heritable disorder of bone formation resulting in low bone mass and a propensity to fracture. It exhibits a broad range of clinical severity, ranging from multiple fracturing in utero and perinatal death to normal adult stature and a low fracture incidence. The disorder is currently classified into seven types based on differences in clinical presentation and bone architecture. Mutation in one of the type I collagen genes is commonly associated with osteogenesis imperfecta, but is not a prerequisite for the diagnosis. Indeed, the newer forms of osteogenesis imperfecta (types V, VI and VII) are not associated with type I collagen gene defects. Amongst the type I collagen gene mutations that can occur, missense base substitutions involving glycine codons in the exons encoding the central triple-helix forming domain predominate. Such mutations can occur in all the classical forms of osteogenesis imperfecta (types I-IV), but genotype/phenotype correlations are complex and often unpredictable. Treatment of osteogenesis imperfecta by bisphosphonate therapy can improve bone mass in all types of the disorder, and while not being a cure for the disorder does improve the quality of life of the patient.
Topics: Genetic Variation; Humans; Mutation, Missense; Osteogenesis Imperfecta
PubMed: 14562271
DOI: 10.22203/ecm.v005a04 -
BMC Musculoskeletal Disorders Jan 2020Osteogenesis Imperfecta (OI) is characterized by bone fragility, and features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short...
BACKGROUND
Osteogenesis Imperfecta (OI) is characterized by bone fragility, and features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short stature can be present. It has long been assumed that the functional ability and quality of life of patients with OI depends primarily on the severity of skeletal deformities. However, fatigue is often mentioned in clinic by patients with all types of OI as an important modifier of their quality of life and does not always seem to be related to their functional ability. The aim of this study is to investigate whether adults with Osteogenesis Imperfecta are significantly more fatigued than the normal population.
METHODS
The Fatigue Severity Scale (FSS) was distributed by mobile phone application among 151 adult patients with different OI types. Results of the FSS in the OI group were compared with two control populations from America (n = 20) and the Netherlands (n = 113).
RESULTS
Ninety-nine patients (OI type 1 (n = 72), OI type 3 (n = 13), OI type 4 (n = 14) completed the FSS questionnaire. The mean FSS score of this cohort was 4.4 and significantly higher than the control populations (2.3/2.9). 65% of our cohort reported at least moderate fatigue compared with 2 control populations from America and the Netherlands.
CONCLUSION
Fatigue in patients with OI is a frequently encountered problem in our expert clinic but research into this topic is sparse. This pilot study is the largest study to date investigating fatigue in patients with OI and results have been compared with two control groups. The mean FSS score of 4.4 in the OI group indicates that people with OI are generally significantly more fatigued than the control population. Further evaluation of fatigue and its influencers in a larger group of OI patients is important for future management.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Phone; Cost of Illness; Cross-Sectional Studies; Fatigue; Female; Health Status; Humans; Male; Middle Aged; Mobile Applications; Osteogenesis Imperfecta; Pilot Projects; Predictive Value of Tests; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Young Adult
PubMed: 31900144
DOI: 10.1186/s12891-019-3000-7 -
American Journal of Obstetrics &... Jul 2021Women with rare diseases, such as osteogenesis imperfecta, may consider pregnancy, although data regarding outcomes, specific risks, and management strategies are...
BACKGROUND
Women with rare diseases, such as osteogenesis imperfecta, may consider pregnancy, although data regarding outcomes, specific risks, and management strategies are lacking.
OBJECTIVE
The Brittle Bone Disorders Consortium of the National Institute of Health Rare Diseases Clinical Research Network established an Osteogenesis Imperfecta Pregnancy Registry to collect and evaluate pregnancy, maternal, and neonatal outcomes in women with osteogenesis imperfecta.
STUDY DESIGN
This was a cross-sectional, survey-based study. Appropriate participants of the Brittle Bone Disorders Consortium Contact Registry were invited to participate in the study. Self-reported information regarding pregnancy characteristics and maternal and neonatal outcomes of women with osteogenesis imperfecta was compared with that of the general population, referenced by literature-based standards. Furthermore, compared with the general population, cohorts of women and fetuses with osteogenesis imperfecta were evaluated to determine whether the presence of osteogenesis imperfecta conveyed an increase in antepartum, intrapartum, and postpartum complications and an increase in adverse neonatal outcomes.
RESULTS
Here, a total 132 participants completed the survey. Compared with the general population, women with osteogenesis imperfecta had higher rates of diabetes in pregnancy (13.3% vs 7%; 95% confidence interval, 7.0-19.6; P=.049), cesarean delivery (68.5% vs 32.7%; 95% confidence interval, 59.9-77.1; P<.001), need for blood transfusion (8.3% vs 1.5%; 95% confidence interval, 3.9-12.8; P=.019), and antepartum and postpartum fractures (relative risk, 221; 95% confidence interval, 59.3-823; P<.001). Maternal hospitalization and cesarean delivery rates were higher in individuals with moderate or severe osteogenesis imperfecta than women who reported mild osteogenesis imperfecta. Neonates born to women with osteogenesis imperfecta had higher risk of being low (26.2% vs 6.8%; P<.001) or very low birthweight (13.8% vs 1.4%; P<.001) infants than the general population. Neonates born to women with osteogenesis imperfecta had a higher rate of neonatal intensive care unit admissions (19% vs 5.68%; P<.001) and higher neonatal mortality at 28 days of life (4.8% vs 0.4%; P=.026), regardless of neonatal osteogenesis imperfecta status.
CONCLUSION
Pregnancies for women with osteogenesis imperfecta are at an increased risk of complications, including hemorrhage, fractures, diabetes mellitus, and increased neonatal morbidity.
Topics: Cesarean Section; Cross-Sectional Studies; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Intensive Care Units, Neonatal; Osteogenesis Imperfecta; Pregnancy
PubMed: 33781976
DOI: 10.1016/j.ajogmf.2021.100362 -
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 -
Journal of Veterinary Diagnostic... May 2022We examined the clinical features and pathology, and identified the causative mutation, of osteogenesis imperfecta in a 2-mo-old kitten with growth retardation and...
We examined the clinical features and pathology, and identified the causative mutation, of osteogenesis imperfecta in a 2-mo-old kitten with growth retardation and abnormal gait. Blood and radiographic examinations were performed on presentation. Radiographs revealed decreased opacity of numerous bones. Fractures were observed in some long bones, including femur and tibia. Histologic examination of the tibia showed decreased osteoid and osteoblasts at the primary spongiosa extending from the growth plate. The periosteum was thickened, and cortical bone and osteoblasts were decreased. Consequently, osteogenesis imperfecta was diagnosed. Genomic DNA and total RNA were extracted from the skin and used for PCR. Whole-genome sequencing identified a 2-bp deletion (c.370_371delTG; p.C124fs), which resulted in a homozygous frameshift mutation on exon 3 of . This mutation introduced a premature stop codon, suggesting production of the truncated protein without a functional domain as a transcription factor for expression of mRNA. This error may have affected collagen fibril formation, leading to the development of osteogenesis imperfecta.
Topics: Animals; Bone and Bones; Cat Diseases; Cats; Female; Mutation; Osteogenesis Imperfecta; Polymerase Chain Reaction
PubMed: 35168412
DOI: 10.1177/10406387221081227 -
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 -
Reumatologia Clinica 2020Osteogenesis 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...
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.
Topics: Adult; Female; Humans; Male; Middle Aged; Osteogenesis Imperfecta; Retrospective Studies; Young Adult
PubMed: 30017614
DOI: 10.1016/j.reuma.2018.05.004 -
British Medical Journal (Clinical... Aug 1984
Topics: Child; Humans; Infant, Newborn; Osteogenesis Imperfecta; Prenatal Diagnosis
PubMed: 6432112
DOI: 10.1136/bmj.289.6442.394 -
Jornal de Pediatria 2020To estimate the prevalence and presentation of bladder, bowel, and combined bladder and bowel symptoms experienced by children with osteogenesis imperfecta and to...
OBJECTIVE
To estimate the prevalence and presentation of bladder, bowel, and combined bladder and bowel symptoms experienced by children with osteogenesis imperfecta and to describe the socio-demographic and clinical profile of these children.
METHOD
A descriptive study was conducted with a convenience sample of parent-child pairs of toilet-trained children aged from 3 to 18 years. Pairs were interviewed using three tools: (1) Socio-Demographic and Clinical Questionnaire; (2) Dysfunctional Voiding Scoring System; (3) Rome III Criteria along with the Bristol Stool Scale. Data were stratified by socio-demographic and clinical variables and analyzed using descriptive statistics.
RESULTS
Thirty-one parent-child pairs participated in the study; 38.7% (n=12) children reported bowel symptoms, 19.4% (n=6) reported a combination of bladder issues (such as holding maneuvers and urgency) and bowel symptoms (such as hard or painful bowel movements and large diameter stools). There were no reports of isolated bladder issues. Among the child participants, 16 (51.7%) identified as female and 20 (64.5%) were 5-14 years old. The most prevalent type of osteogenesis imperfecta was type III (n=12; 38.7%) and eight (25.8%) children reported using a wheelchair.
CONCLUSION
This is the first study to examine the prevalence and presentation of bladder, bowel, and combined bladder and bowel symptoms in children with osteogenesis imperfecta, offering a preliminary socio-demographic and clinical profile of these children. This research is an important step toward effective screening, detection, and access to care and treatment, especially for clinicians working with this group of very fragile patients.
Topics: Adolescent; Child; Child, Preschool; Constipation; Female; Humans; Male; Osteogenesis Imperfecta; Prevalence; Surveys and Questionnaires; Urinary Bladder
PubMed: 30802423
DOI: 10.1016/j.jped.2018.12.008 -
Nature Reviews. Endocrinology Jun 2011A new paradigm has emerged for osteogenesis imperfecta as a collagen-related disorder. The more prevalent autosomal dominant forms of osteogenesis imperfecta are caused... (Review)
Review
A new paradigm has emerged for osteogenesis imperfecta as a collagen-related disorder. The more prevalent autosomal dominant forms of osteogenesis imperfecta are caused by primary defects in type I collagen, whereas autosomal recessive forms are caused by deficiency of proteins which interact with type I procollagen for post-translational modification and/or folding. Factors that contribute to the mechanism of dominant osteogenesis imperfecta include intracellular stress, disruption of interactions between collagen and noncollagenous proteins, compromised matrix structure, abnormal cell-cell and cell-matrix interactions and tissue mineralization. Recessive osteogenesis imperfecta is caused by deficiency of any of the three components of the collagen prolyl 3-hydroxylation complex. Absence of 3-hydroxylation is associated with increased modification of the collagen helix, consistent with delayed collagen folding. Other causes of recessive osteogenesis imperfecta include deficiency of the collagen chaperones FKBP10 or Serpin H1. Murine models are crucial to uncovering the common pathways in dominant and recessive osteogenesis imperfecta bone dysplasia. Clinical management of osteogenesis imperfecta is multidisciplinary, encompassing substantial progress in physical rehabilitation and surgical procedures, management of hearing, dental and pulmonary abnormalities, as well as drugs, such as bisphosphonates and recombinant human growth hormone. Novel treatments using cell therapy or new drug regimens hold promise for the future.
Topics: Animals; Collagen Type I; Humans; Osteogenesis Imperfecta; Protein Processing, Post-Translational
PubMed: 21670757
DOI: 10.1038/nrendo.2011.81