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Endocrine Journal Aug 2023Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder that affects 6-7 per 100,000 populations, and pituitary stalk interruption syndrome (PSIS) is a...
Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder that affects 6-7 per 100,000 populations, and pituitary stalk interruption syndrome (PSIS) is a rare congenital defect with varying degrees of pituitary hormone deficiency, affecting approximately 0.5 in every 100,000 births. Currently, only two cases of these complications have been reported. A 46-year-old male who had experienced more than 20 fractures (peripheral and vertebral) during adolescence visited our hospital for close examination. He presented with blue sclerae and long bone deformations. We suspected OI because his mother and sister, who were being treated for osteoporosis, also had blue sclerae. Genetic testing identified a heterozygous variant (c.757C > T, p.Arg253Ter) in the COL1A1 gene, leading to the diagnosis of OI. His mother and sister also had the same variant. Considering that he underwent GH replacement therapy for his short stature during his childhood, his pituitary hormone levels were also evaluated to know if GH deficiency impacted low bone density; hypopituitarism was then suspected. The pituitary function test results led to the diagnoses of hypothalamic GH deficiency, hypogonadism, hypothyroidism, and hypoadrenocorticism. Furthermore, magnetic resonance imaging showed anterior pituitary atrophy, pituitary stalk loss, and ectopic posterior pituitary, leading to the diagnosis of PSIS. The combination of OI and hypopituitarism may have caused further bone fragility. Therefore, although rare, clinicians should keep in mind that patients with OI can possibly have concomitant pituitary insufficiency, which can lead to developmental and growth retardation.
Topics: Male; Adolescent; Humans; Child; Middle Aged; Osteogenesis Imperfecta; Pituitary Diseases; Pituitary Gland; Hypopituitarism; Pituitary Hormones
PubMed: 37183013
DOI: 10.1507/endocrj.EJ22-0564 -
JBMR Plus Dec 2023Osteogenesis imperfecta (OI) is a genetic, collagen-related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical...
Osteogenesis imperfecta (OI) is a genetic, collagen-related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical behavior remains unclear. The extracellular matrix (ECM) of OI bone exhibits a higher degree of bone mineralization (DBM), whereas compressive mechanical properties at the ECM level do not appear to be inferior to healthy bone. However, it is unknown if collagen defects alter ECM tensile properties. This study aims to quantify the tensile properties of healthy and OI bone ECM. In three transiliac biopsies (healthy = 1, OI type I = 1, OI type III = 1), 23 microtensile specimens (gauge dimensions 10 × 5 × 2 μm) were manufactured and loaded quasi-statically under tension in vacuum condition. The resulting loading modulus and ultimate strength were extracted. Interestingly, tensile properties in OI bone ECM were not inferior compared to controls. All specimens revealed a brittle failure behavior. Fracture surfaces were graded according to their mineralized collagen fibers (MCF) orientation into axial, mixed, and transversal fracture surface types (FST). Furthermore, tissue mineral density (TMD) of the biopsy cortices was extracted from micro-computed tomogra[hy (μCT) images. Both FST and TMD are significant factors to predict loading modulus and ultimate strength with an adjusted of 0.556 ( = 2.65e-05) and 0.46 ( = 2.2e-04), respectively. The influence of MCF orientation and DBM on the mechanical properties of the neighboring ECM was further verified with quantitative polarized Raman spectroscopy (qPRS) and site-matched nanoindentation. MCF orientation and DBM were extracted from the qPRS spectrum, and a second mechanical model was developed to predict the indentation modulus with MCF orientation and DBM ( = 67.4%, = 7.73e-07). The tensile mechanical properties of the cortical bone ECM of two OI iliac crest biopsies are not lower than the one from a healthy and are primarily dependent on MCF orientation and DBM. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 38130764
DOI: 10.1002/jbm4.10826 -
European Journal of Medical Genetics Oct 2023The linkeropathies are a group of rare disorders, characterized by overlapping clinical features involving the skeletal and connective tissues. Each "linker" gene...
The linkeropathies are a group of rare disorders, characterized by overlapping clinical features involving the skeletal and connective tissues. Each "linker" gene encodes an enzyme responsible for the addition of glycosaminoglycan chains to proteoglycans via a common tertrasaccharine linker region. The original descriptions of the autosomal recessive B3GALT6-related disorder showed that the associated clinical features are pleiotropic, spanning the skeletal dysplasia (Spondyloepimetaphyseal dysplasia with joint laxity) (SEMD-JL1) and connective tissue disorder (Ehlers-Danlos syndrome) (EDS spondylodysplastic Type 2) spectrum. Here, we describe three patients with biallelic B3GALT6 variants: each had different clinical presentations, and the two older patients initially received alternative clinical diagnoses (Larsen syndrome and Osteogenesis imperfecta, respectively). We describe the clinico-radiological features of these patients to highlight the spectrum of disease associated with the B3GALT6-linkeropathy.
PubMed: 37657630
DOI: 10.1016/j.ejmg.2023.104829 -
Health and Quality of Life Outcomes Jul 2023This study assesses the association between health-related quality of life (HRQoL) for pediatric patients with osteogenesis imperfecta (OI) and their caregivers' eHealth...
OBJECTIVE
This study assesses the association between health-related quality of life (HRQoL) for pediatric patients with osteogenesis imperfecta (OI) and their caregivers' eHealth literacy (eHL), financial well-being, and mental health along with the impact of eHealth literacy on the financial well-being and mental health of OI caregivers.
METHODS
Participants were recruited from a member pool of two OI patient organizations in China. Information about patients' HRQoL and their caregivers' eHL, financial well-being, and mental health was collected. Structure equation modeling (SEM) was used to estimate the relationship between the measures. The robust weighted least square mean and variance adjusted estimator was used. Three criteria, the comparative fit index, the Tucker-Lewis index, and the root mean square error of approximation, were used to evaluate the goodness-of-fit of the model.
RESULTS
A total of 166 caregivers completed the questionnaires. Around 28.3% indicated that pediatric OI patients experienced problems related to mobility, and 25.3% reported difficulty doing usual activities. Around 52.4% of caregivers reported that their care receivers have some emotional problems while 8.4% reported that their care receivers have "a lot of" emotional problems. 'Some problems' on all dimensions on EQ-5D-Y was the most frequently reported health state (13.9%), and around 10.0% have no problems on all dimensions on EQ-5D-Y. Caregivers tended to show a significantly high eHL, financial well-being, and mental health when their care receivers reported no problems with usual activities and emotions. The SEM demonstrated a significant and positive relationship between eHL, financial well-being, and mental health.
CONCLUSION
OI caregivers with high eHL reported satisfactory financial well-being and mental health; their care receivers rarely reported living with poor HRQoL. Providing multicomponent and easy-to-learn training to improve caregivers' eHL should be highly encouraged.
Topics: Humans; Child; Quality of Life; Caregivers; Mental Health; Osteogenesis Imperfecta; Literacy; Surveys and Questionnaires
PubMed: 37420281
DOI: 10.1186/s12955-023-02148-4 -
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 -
Cureus Sep 2023Introduction The treatment of musculoskeletal pathologies in osteogenesis imperfecta aims to provide the maximum possible function by preventing bone fractures and...
Introduction The treatment of musculoskeletal pathologies in osteogenesis imperfecta aims to provide the maximum possible function by preventing bone fractures and progressive deformities. Despite the development of implants used in the surgical treatment of osteogenesis imperfecta, there is no consensus on the most appropriate method for the correction of skeletal deformities. The aim of this study was to compare telescopic and non-telescopic implants in terms of postoperative complications. Methods Twenty-three patients who were operated on for the diagnosis of osteogenesis imperfecta between 2005 and 2018 were retrospectively analyzed. Demographic data, follow-up times, and the total number of surgeries and complications were recorded. The operated bones were divided into two groups according to whether the intramedullary fixation material used was telescopic or not. Results Twenty-one of 23 patients were included in the study due to the use of intramedullary fixation material in the operation. The mean age was 10.1 ± 2.9 years, and the mean follow-up period was 8.9 ± 3.5 years. Intramedullary fixation was applied to 43 long bones in 21 patients due to fracture or deformity. At least one complication was encountered in nine of 14 bones with telescopic implants and in 27 of 29 bones with non-telescopic implants. Major complications requiring surgical treatment were seen in seven bones of the telescopic implant group and 27 bones of the non-telescopic implant group. Conclusion The use of telescopic implants relatively reduces the complication rate and the need for repetitive surgery in patients with a diagnosis of osteogenesis imperfecta. However, the number of complications is still as high as with non-telescopic implants.
PubMed: 37731684
DOI: 10.7759/cureus.45376 -
Cureus Mar 2024The Golgi apparatus is an organelle responsible for protein processing, sorting, and transport in cells. Recent research has shed light on its possible role in the... (Review)
Review
The Golgi apparatus is an organelle responsible for protein processing, sorting, and transport in cells. Recent research has shed light on its possible role in the pathogenesis of various bone diseases. This review seeks to explore its significance in osteoporosis, osteogenesis imperfecta, and other bone conditions such as dysplasias. Numerous lines of evidence demonstrate that perturbations to Golgi apparatus function can disrupt post-translational protein modification, folding and trafficking functions crucial for bone formation, mineralization, and remodeling. Abnormalities related to glycosylation, protein sorting, or vesicular transport in Golgi have been associated with altered osteoblast and osteoclast function, compromised extracellular matrix composition, as well as disrupted signaling pathways involved with homeostasis of bones. Mutations or dysregulation of Golgi-associated proteins, including golgins and coat protein complex I and coat protein complex II coat components, have also been implicated in bone diseases. Such genetic alterations may disrupt Golgi structure, membrane dynamics, and protein transport, leading to bone phenotype abnormalities. Understanding the links between Golgi apparatus dysfunction and bone diseases could provide novel insights into disease pathogenesis and potential therapeutic targets. Future research should focus on unraveling specific molecular mechanisms underlying Golgi dysfunction associated with bone diseases to develop targeted interventions for restoring normal bone homeostasis while decreasing clinical manifestations associated with these issues.
PubMed: 38665758
DOI: 10.7759/cureus.56982 -
MethodsX Dec 2023Lamellar bone formed in individuals with moderate and severe osteogenesis imperfecta (OI) is often composed of lamellae that are structurally abnormal. Measuring the...
Lamellar bone formed in individuals with moderate and severe osteogenesis imperfecta (OI) is often composed of lamellae that are structurally abnormal. Measuring the thickness of these lamellae can be helpful in assessing the effect of specific collagen and collagen-related mutations on OI bone synthesis. Manual measurement of lamellar thicknesses in large quantities is very time consuming. The method for automated measurement described in this article utilizes an image processing script to identify the average thickness of multiple lamellae automatically from histologic images of bone. This allows for faster measurements that are less prone to human error and can account for variability in the thickness of a lamella along its length.•OI and control bone samples are prepared per the glycol methacrylate resin (JB-4 plastic) technique and viewed using polarized light microscopy.•Ideal bone regions for measurement are identified using specific qualitative criteria designed to ensure uniform and accurate thickness measurements.•The method was validated with dataset containing 211 lamellae from control bone and 212 lamellae from OI bone.
PubMed: 37954966
DOI: 10.1016/j.mex.2023.102428 -
Orphanet Journal of Rare Diseases Sep 2023Skeletal dysplasias are a diverse group of rare disorders in the chondro-osseous tissue that can have a significant impact on patient's functionality. The worldwide...
BACKGROUND
Skeletal dysplasias are a diverse group of rare disorders in the chondro-osseous tissue that can have a significant impact on patient's functionality. The worldwide prevalence of skeletal dysplasias at birth is approximately 1:5000 births. To date, disease burden and trends of skeletal dysplasias in the Sri Lankan population have not been described in any epidemiological study. Our aim was to evaluate the burden and the current trends in hospital admissions for skeletal dysplasias in the Sri Lankan population. A retrospective evaluation of hospital admissions for skeletal dysplasia during 2017-2020 was performed using population-based data from the eIMMR database which covers government hospitals in the entire country. The trends in hospital admissions for skeletal dysplasias by calendar year, age, and types of skeletal dysplasia were described using appropriate summary statistics.
RESULTS
Respective crude admission rates of skeletal dysplasias in the years 2017, 2018, 2019 and 2020 were 5.2, 8.1, 8.0, and 6.5 per million population. A female predominance (1.4:1) was noted during the studied period. Of all reported cases the majority (n = 268; 44.2%) were children less than 4 years. Each year, 0-4 years age group represented 40-47% of the total hospital admissions. More than half of the cases were reported from Colombo (28.1%) and Kandy (25.4%) districts combined. 60% of cases were diagnosed as osteogenesis imperfecta (OI). Rising trends were observed in the hospital admissions for osteogenesis imperfecta, achondroplasia and osteopetrosis, while other skeletal dysplasia types collectively showed a relatively stable trend.
CONCLUSION
This preliminary study revealed a female predominance of skeletal dysplasias and a relatively high admission rate of osteogenesis imperfecta in the Sri Lankan population. A distinct trend was not visible in the studied years probably due to the impact on hospital services due to COVID- Pandemic. Future research on the healthcare burden on families affected by skeletal dysplasia is required to better understand the overall cost of care and identify therapies that reduce admission rates. This study highlights the value of analysing population-based data on rare diseases to improve healthcare in low-resource countries.
Topics: Infant, Newborn; Child; Female; Humans; Male; Osteogenesis Imperfecta; Sri Lanka; Retrospective Studies; COVID-19; Osteochondrodysplasias; Hospitals
PubMed: 37684696
DOI: 10.1186/s13023-023-02884-2 -
PloS One 2023Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray...
Association of trabecular bone score and bone mineral apparent density with the severity of bone fragility in children and adolescents with osteogenesis imperfecta: A cross-sectional study.
Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray absorptiometry (DXA), is used to assess bone brittleness. The height-adjusted BMD Z-score (BMDHAZ) is calculated in children and adolescents with OI to reduce the confounding factor of short stature. However, even with the BMDHAZ, severity evaluation in children and adolescents with OI is challenging because certain abnormalities in bone quality cannot be accurately assessed by BMD analysis. The trabecular bone scores (TBS) and bone mineral apparent density (BMAD), which represent the structural integrity of bone and bone-size-associated BMD, respectively, are associated with fracture risk. Recently, age- and sex-specific reference ranges have been reported, enabling the calculation of Z-scores for children. To evaluate which density measurements show the highest correlation with fracture risk, we analyzed the associations between the Z-scores of TBS, BMAD, and BMDHAZ, fracture rate, and genetic variants. We retrospectively reviewed 42 participants with OI aged 5 to 20 years who underwent DXA. COL1A1/2 pathogenic variants were detected in 41 of the 42 participants. In participants with nonsense and frameshift variants (n = 17) resulting in haploinsufficiency and mild phenotype, the TBS Z-score was negatively correlated with fracture rate (FR) (r = -0.50, p = 0.042). In participants with glycine substitution (n = 9) causing the severe phenotype, the BMAD Z-scores were negatively correlated with FR (r = -0.74, p = 0.022). No correlation between the BMDHAZ and FR was observed in both groups. These findings suggest that the TBS and BMAD are useful in assessing children and adolescents with OI with specific genetic variants.
Topics: Female; Male; Humans; Bone Density; Cancellous Bone; Cross-Sectional Studies; Osteogenesis Imperfecta; Retrospective Studies; Fractures, Bone; Minerals
PubMed: 37643181
DOI: 10.1371/journal.pone.0290812