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Calcified Tissue International Mar 2024Osteogenesis imperfecta (OI) is a rare genetic disorder caused by abnormal collagen type I production. While OI is primarily characterized by bone fragility and... (Review)
Review
Osteogenesis imperfecta (OI) is a rare genetic disorder caused by abnormal collagen type I production. While OI is primarily characterized by bone fragility and deformities, patients also have extraskeletal manifestations, including an increased risk of cardiovascular disease. This review provides a comprehensive overview of the literature on cardiovascular diseases in OI patients in order to raise awareness of this understudied clinical aspect of OI and support clinical guidelines. In accordance with the PRISMA guidelines, a systematic literature search in PubMed, Embase, Web of Science and Scopus was conducted that included articles from the inception of these databases to April 2023. Valvular disease, heart failure, atrial fibrillation, and hypertension appear to be more prevalent in OI than in control individuals. Moreover, a larger aortic root was observed in OI compared to controls. Various cardiovascular diseases appear to be more prevalent in OI than in controls. These cardiovascular abnormalities are observed in all types of OI and at all ages, including young children. As there are insufficient longitudinal studies, it is unknown whether these abnormalities are progressive in nature in OI patients. Based on these findings, we would recommend referring individuals with OI to a cardiologist with a low-threshold.
Topics: Child; Humans; Child, Preschool; Osteogenesis Imperfecta; Cardiovascular Diseases; Cardiovascular Abnormalities; Collagen Type I; Longitudinal Studies
PubMed: 38243143
DOI: 10.1007/s00223-023-01171-3 -
Journal of Applied Oral Science :... 2023Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as brittle bone disease.
OBJECTIVE
This study aims to describe the prevalence of dental anomalies (except dentinogenesis imperfecta) in individuals with OI, and compare the prevalence of dental anomalies between individuals with and without OI and between individuals with different types of OI.
SEARCH METHODS
Searches in PubMed, Web of Science, Scopus, Ovid, and gray literature were performed in October 2022.
SELECTION CRITERIA
Observational studies (with or without a comparison group) that evaluated the prevalence of dental anomalies in individuals with OI. Data collection and analysis: Data items were extracted by two authors. Quality assessment employing the Joanna Briggs Institute checklists and meta-analyses was conducted. Results were provided in prevalence values and odds ratio (OR) / 95% confidence interval (CI). Strength of evidence was determined.
RESULTS
Eighteen studies were included. Most prevalent dental anomalies in individuals with OI included pulp obliteration (46.4%), dental impaction (33.5%), dental impaction of second molars (27%), and tooth agenesis (23.9%). Individuals with OI type III/IV had 20.16-fold greater chance of exhibiting tooth discoloration in comparison with individuals with OI type I (CI: 1.10-370.98). In comparison with the group without OI, the individuals with OI had 6.90-fold greater chance of exhibiting dental impaction (CI: 1.54-31.00). High methodological quality was found in 47% of the studies. Strength of evidence was low or very low.
CONCLUSIONS
Pulp obliteration, dental impaction, and tooth agenesis were the most prevalent dental anomalies in the OI group. Individuals with OI were more likely to have dental impaction than individuals without OI. Individuals with OI type III/IV (severe-moderate) are more likely to have tooth discoloration than individuals with OI type I (mild).
Topics: Humans; Osteogenesis Imperfecta; Prevalence; Tooth Discoloration
PubMed: 37672427
DOI: 10.1590/1678-7757-2023-0040 -
Journal of Clinical Medicine Feb 2023Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles.
PubMed: 36835951
DOI: 10.3390/jcm12041416 -
Orphanet Journal of Rare Diseases Feb 2023Osteogenesis imperfecta (OI) is a rare, connective tissue disorder characterised by bone fragility, resulting in recurrent fractures and skeletal deformities....
BACKGROUND
Osteogenesis imperfecta (OI) is a rare, connective tissue disorder characterised by bone fragility, resulting in recurrent fractures and skeletal deformities. Extra-skeletal manifestations include dentinogenesis imperfecta, hearing abnormalities and lung disease. These co-morbidities combined with recurrent fractures can exert a significant impact on health-related quality of life (HR-QOL). It is important to assess HR-QOL throughout adulthood because the prevalence of some OI-specific complications increases with age.
METHODS
PubMed, EMBASE and CENTRAL databases were searched on 2nd February 2022 to identify studies reporting quantitative assessments of HR-QOL in adults with OI. The primary endpoint was to determine the impact of an OI diagnosis on adult's HR-QOL. Secondary endpoints were to (i) examine how frequently various HR-QOL assessment tools were used (ii) identify differences in HR-QOL between OI types and (iii) investigate the determinants of HR-QOL in adults with OI. Search results were exported to Endnote where two reviewers independently conducted title/abstract and full-text reviews. Data from accepted studies were extracted into Microsoft Excel. A narrative synthesis was then undertaken.
RESULTS
The review identified 17 studies with a total of 1,648 adults. The Short Form-36 (SF-36) was the most frequently reported HR-QOL assessment tool and was used in nine studies. Physical HR-QOL was reduced in adults with OI. Physical component scores (PCS) or individual physical domains of the SF-36 were lower in eight of nine studies. Mental component scores (MCS) were preserved in all six studies, however individual mental health domains of the SF-36 were reduced in some studies. The prevalence of anxiety/depression was relatively low in adults with OI. Those with type III OI had lower physical and respiratory HR-QOL but preserved mental HR-QOL compared with type I. The prevalence of fatigue and pain was higher in adults with OI compared with reference populations. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.
CONCLUSION
OI in adulthood has a wide-ranging negative impact on HR-QOL. Physical and respiratory HR-QOL were lower, while the prevalence of pain and fatigue were higher than in reference populations. Mental HR-QOL was relatively preserved, although some deficits were identified. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.
Topics: Adult; Humans; Osteogenesis Imperfecta; Quality of Life; Pain; Fatigue; Prevalence
PubMed: 36814291
DOI: 10.1186/s13023-023-02643-3 -
Orphanet Journal of Rare Diseases Feb 2023Osteogenesis imperfecta (OI) is a rare heritable connective tissue disorder primarily characterised by skeletal deformity and fragility, and an array of secondary... (Review)
Review
BACKGROUND
Osteogenesis imperfecta (OI) is a rare heritable connective tissue disorder primarily characterised by skeletal deformity and fragility, and an array of secondary features. The purpose of this review was to capture and quantify the published evidence relating specifically to the clinical, humanistic, and economic impact of OI on individuals, their families, and wider society.
METHODS
A systematic scoping review of 11 databases (MEDLINE, MEDLINE in-progress, EMBASE, CENTRAL, PsycINFO, NHS EED, CEA Registry, PEDE, ScHARRHUd, Orphanet and Google Scholar), supplemented by hand searches of grey literature, was conducted to identify OI literature published 1st January 1995-18th December 2021. Searches were restricted to English language but without geographical limitations. The quality of included records was assessed using the AGREE II checklist and an adapted version of the JBI cross-sectional study checklist.
RESULTS
Of the identified 7,850 records, 271 records of 245 unique studies met the inclusion criteria; overall, 168 included records examined clinical aspects of OI, 67 provided humanistic data, 6 reported on the economic impact of OI, and 30 provided data on mixed outcomes. Bone conditions, anthropometric measurements, oral conditions, diagnostic techniques, use of pharmacotherapy, and physical functioning of adults and children with OI were well described. However, few records included current care practice, diagnosis and monitoring, interactions with the healthcare system, or transition of care across life stages. Limited data on wider health concerns beyond bone health, how these concerns may impact health-related quality of life, in particular that of adult men and other family members, were identified. Few records described fatigue in children or adults. Markedly few records provided data on the socioeconomic impact of OI on patients and their caregivers, and associated costs to healthcare systems, and wider society. Most included records had qualitative limitations.
CONCLUSION
Despite the rarity of OI, the volume of recently published literature highlights the breadth of interest in the OI field from the research community. However, significant data gaps describing the experience of OI for individuals, their families, and wider society warrant further research to capture and quantify the full impact of OI.
Topics: Adult; Male; Child; Humans; Osteogenesis Imperfecta; Quality of Life; Cross-Sectional Studies; Socioeconomic Factors
PubMed: 36814274
DOI: 10.1186/s13023-023-02627-3 -
Scientific Reports Oct 2022About 70% of people with osteogenesis imperfecta (OI) experience hearing loss. There is no cure for OI, and therapies to ameliorate hearing loss rely on conventional... (Meta-Analysis)
Meta-Analysis
About 70% of people with osteogenesis imperfecta (OI) experience hearing loss. There is no cure for OI, and therapies to ameliorate hearing loss rely on conventional treatments for auditory impairments in the general population. The success rate of these treatments in the OI population with poor collagenous tissues is still unclear. Here, we conduct a systematic review and meta-analysis on the efficacy of treatments addressing hearing loss in OI. This study conforms to the reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Data sources include published articles in Medline via PubMed, Web of Science, Scopus, and Embase, from their inception to November 2020. Studies included individuals with OI undergoing a hearing loss treatment, having pre- and postoperative objective assessment of hearing function at a specified follow-up length. Our search identified 1144 articles, of which 67 were reviewed at full-text screening. A random-effects meta-analysis was conducted on the selected articles (n = 12) of people with OI that underwent stapes surgery. Success was assessed as the proportion of ears with a postoperative Air-Bone Gap (ABG) ≤ 10 dB. A systematic review was conducted on the remaining articles (n = 13) reporting on other treatments. No meta-analysis was conducted on the latter due to the low number of articles on the topic and the nature of single case studies. The meta-analysis shows that stapes surgeries have a low success rate of 59.08 (95% CI 45.87 to 71.66) in the OI population. The systematic review revealed that cochlear implants, bone-anchored hearing aids, and other implantable hearing aids proved to be feasible, although challenging, in the OI population, with only 2 unsuccessful cases among the 16 reviewed single cases. This analysis of published data on OI shows poor clinical outcomes for the procedures addressing hearing loss. Further studies on hearing loss treatments for OI people are needed. Notably, the mechanisms of hearing loss in OI need to be determined to develop successful and possibly non-invasive treatment strategies.
Topics: Cochlear Implantation; Deafness; Hearing Loss; Humans; Osteogenesis Imperfecta; Stapes Surgery
PubMed: 36224204
DOI: 10.1038/s41598-022-20169-9 -
American Journal of Obstetrics and... Apr 2023This study aimed to determine the incremental yield of prenatal exome sequencing over chromosomal microarray or G-banding karyotype in fetuses with: (1) intrauterine... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine the incremental yield of prenatal exome sequencing over chromosomal microarray or G-banding karyotype in fetuses with: (1) intrauterine growth restriction related to placental insufficiency or (2) short long bones, in isolated and nonisolated instances for both scenarios.
DATA SOURCES
Data were collected via electronic searches for relevant citations from January 2010 to April 10, 2022 in MEDLINE, Embase, Web of Science, and Cochrane, and using relevant bibliographies and data generated in-house.
STUDY ELIGIBILITY CRITERIA
Included were prospective or retrospective cohort studies and/or case series with: (1) n>5 cases of short long bones and/or intrauterine growth restriction undergoing prenatal sequencing with a clearly defined phenotype including assessment of placental function; (2) testing based on prenatal phenotype only; (3) a nondiagnostic chromosomal microarray/karyotype; and (4) known results of genetic testing.
METHODS
Incremental yield was calculated for each study and as a pooled value for the aforementioned groups using a random-effects model. Results were displayed in forest plots with 95% confidence intervals. Heterogeneity was assessed statistically using Higgins' I. Publication bias was assessed graphically using funnel plots. Quality assessment was performed using modified Standards for Reporting of Diagnostic Accuracy criteria (International Prospective Register of Systematic Reviews registration number CRD42022324680).
RESULTS
Nineteen studies were included (n=452 cases). The apparent incremental yields with prenatal sequencing were: (1) 4% (95% confidence interval, -5.0 to 12; I=0%) in isolated intrauterine growth restriction with evidence of placental insufficiency, (2) 30% (95% confidence interval, 13-47; I=1%) in intrauterine growth restriction with additional structural anomalies, (3) 48% (95% confidence interval, 26-70; I=73%) in isolated short long bones, and (4) 68% (95% confidence interval, 58-77; I=51%) in short long bones with additional skeletal anomalies. Of the 37 short long bone cases with a diagnosis, 32 had a skeletal dysplasia, with thanatophoric dysplasia and osteogenesis imperfecta being the most common (both 21.6% [n=8/37]). In fetuses with short long bones and additional skeletal features, osteogenesis imperfecta was the most common diagnosis (28% [n=57/204]). Where documented, the inheritance patterns were de novo in 75.4% (n=150) of cases.
CONCLUSION
Prenatal sequencing adds substantially to incremental yield over chromosomal microarray in fetuses with short long bones or multisystem intrauterine growth restriction. Robust studies are required to assess the utility of fetal sequencing in isolated intrauterine growth restriction with evidence of placental insufficiency, which cannot be recommended on the basis of current evidence.
Topics: Humans; Pregnancy; Female; Fetal Growth Retardation; Placental Insufficiency; Exome Sequencing; Retrospective Studies; Osteogenesis Imperfecta; Placenta; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 36209938
DOI: 10.1016/j.ajog.2022.09.045 -
Frontiers in Immunology 2022Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet... (Meta-Analysis)
Meta-Analysis
Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet medical need. Common sources of MSCs include among others, bone marrow (BM), fat, umbilical cord, and placenta-derived decidua stromal cells (DSCs). We here summarize our more than 20-years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. BM-MSCs were first explored to enhance the engraftment of autografts in hematopoietic cell transplantation (HCT) and osteogenesis imperfecta around 30 years ago. In 2004, our group reported the first anti-inflammatory use of BM-MSCs in a child with grade IV acute graft-versus-host disease (GvHD). Subsequent studies have shown that MSCs appear to be more effective in acute than chronic GvHD. Today BM-MSC-therapy is registered for acute GvHD in Japan and for GvHD in children in Canada and New Zeeland. MSCs first home to the lung following intravenous injection and exert strong local and systemic immunomodulatory effects on the host immune system. Thus, they were studied for ameliorating the cytokine storm in acute respiratory distress syndrome (ARDS). Both, MSCs and DSCs were used to treat SARS-CoV-2 coronavirus-induced disease 2019 (COVID-19)-induced ARDS. In addition, they were also used for other novel indications, such as pneumomediastinum, colon perforation, and radiculomyelopathy. MSC and DSCs trigger coagulation and were thus explored to stop hemorrhages. DSCs appear to be more effective for acute GvHD, ARDS, and hemorrhages, but randomized studies are needed to prove superiority. Stromal cell infusion is safe, well tolerated, and only gives rise to a slight fever in a limited number of patients, but no major side effects have been reported in multiple safety studies and metaanalysis. In this review we summarize current evidence from studies, animal models, and importantly our clinical experience, to support stromal cell therapy in multiple clinical indications. This encloses MSC's effects on the immune system, coagulation, and their safety and efficacy, which are discussed in relation to prominent clinical trials within the field.
Topics: Animals; COVID-19; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pregnancy; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 35371003
DOI: 10.3389/fimmu.2022.839844 -
International Journal of Environmental... Jan 2022The aim of this systematic review was to answer the question of whether patients with osteogenesis imperfecta can be prosthetically rehabilitated with dental implants. A... (Review)
Review
The aim of this systematic review was to answer the question of whether patients with osteogenesis imperfecta can be prosthetically rehabilitated with dental implants. A protocol was prospectively registered in PROSPERO (CRD42021286368). The inclusion criteria were the presence of osteogenesis imperfecta and the use of implants for prosthetic restorations. Cases in which the inclusion criteria were not met were excluded. PubMed, Web of Science, and Scopus were last searched on 22 August 2021. Quality assessment was performed using the Methodological Quality and Synthesis of Case Series and Case Reports tool. The primary outcome was implant survival. Supporting data were analyzed descriptively. Twelve studies were included. Twenty-three patients received a total number of 116 implants, with 5.0 (±3.8) implants placed per patient. The implant survival rate was 94.0% with a mean follow-up of 59.1 months (±36.1). A limitation of this review was the relatively short follow-up time in some of the included studies; therefore, the survival rate may be overestimated. Nevertheless, the available data showed the loss of only seven implants, with two implants lost due to implant fractures not attributable to the patient. With the limitations of this review and based on the available data, dental implants have a high survival rate in patients with osteogenesis imperfecta. Therefore, dental implants may be a viable treatment option for replacing missing teeth. This research was not funded by external resources.
Topics: Dental Implants; Dental Restoration Failure; Humans; Osteogenesis Imperfecta
PubMed: 35162583
DOI: 10.3390/ijerph19031563 -
Annals of Medicine Dec 2021Respiratory failure is a major cause of death in patients with Osteogenesis Imperfecta. Moreover, respiratory symptoms seem to have a dramatic impact on their quality of...
INTRODUCTION
Respiratory failure is a major cause of death in patients with Osteogenesis Imperfecta. Moreover, respiratory symptoms seem to have a dramatic impact on their quality of life. It has long been thought that lung function disorders in OI are mainly due to changes in the thoracic wall, caused by bone deformities. However, recent studies indicate that alterations in the lung itself can also undermine respiratory health.
OBJECTIVES
Is there any intrapulmonary alteration in Osteogenesis Imperfecta that can explain decreased pulmonary function? The aim of this systematic literature review is to investigate to what extent intrapulmonary or extrapulmonary thoracic changes contribute to respiratory dysfunction in Osteogenesis Imperfecta.
METHODS
A literature search (in PubMed, Embase, Web of Science, and Cochrane), which included articles from inception to December 2020, was performed in accordance with the PRISMA guidelines.
RESULTS
Pulmonary function disorders have been described in many studies as secondary to scoliosis or to thoracic skeletal deformities. The findings of this systematic review suggest that reduced pulmonary function can also be caused by a primary pulmonary problem due to intrinsic collagen alterations.
CONCLUSIONS
Based on the most recent studies, the review indicates that pulmonary defects may be a consequence of abnormal collagen type I distorting the intrapulmonary structure of the lung. Lung function deteriorates further when intrapulmonary defects are combined with severe thoracic abnormalities. This systematic review reveals novel findings of the underlying pathological mechanism which have clinical and diagnostic implications for the assessment and treatment of pulmonary function disorders in Osteogenesis Imperfecta.KEY MESSAGESDecreased pulmonary function in Osteogenesis Imperfecta can be attributed to primary pulmonary defects due to intrapulmonary collagen alterations and not solely to secondary problems arising from thoracic skeletal dysplasia.Type I collagen defects play a crucial role in the development of the lung parenchyma and defects, therefore, affect pulmonary function. More awareness is needed among physicians about pulmonary complications in Osteogenesis Imperfecta to develop novel concepts on clinical and diagnostic assessment of pulmonary functional disorders.
Topics: Humans; Lung; Osteogenesis Imperfecta; Quality of Life; Respiratory Function Tests; Respiratory Insufficiency; Scoliosis
PubMed: 34569391
DOI: 10.1080/07853890.2021.1980819