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Journal of Clinical Research in... Jun 2024Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone...
INTRODUCTION
Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients with targeted next-generation sequencing (NGS).
METHOD
In patients with OI, a targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform.
RESULTS
Fifty-six patients (female/male: 25/31) from 46 different families were enrolled in the study. Consanguinity between parents was noted in 15 (32.6%) families. Clinically according to Sillence classification; 18(33.1%) patients were considered to type I, 1(1.7%) type II, 26(46.4%) type III and 11(19.6%) type IV. Median body weight was -1.1 (-6.8, - 2.5) SDS, and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity was detected in 30 (53.5%) of the patients, while 31 (55.4%) were evaluated as mobile. Thirty-six (60.7%) patients had blue sclera, 13 (23.2%) had scoliosis, 12 (21.4%) had dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 genes were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes (FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected in all investigated genes were not previously reported in the literature and were classified to be pathogenic according to ACMG guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in a total of 13 OI genes included in the panel.
CONCLUSION
Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. In addition, 9 new variants were assessed in known OI genes which is a significant contribution to the literature.
PubMed: 38828893
DOI: 10.4274/jcrpe.galenos.2024.2022-12-8 -
Calcified Tissue International Mar 2024There are no licensed treatments for children with osteogenesis imperfecta. Children currently receive off-label treatment with bisphosphonates, without any consistent... (Review)
Review
There are no licensed treatments for children with osteogenesis imperfecta. Children currently receive off-label treatment with bisphosphonates, without any consistent approach to dose, drug or route of administration. Meta-analyses suggest that anti-fracture efficacy of such interventions is equivocal. New therapies are undergoing clinical trials, and it is likely that one or more will receive marketing authorisation within the next three to five years. The long-term outcome from such interventions will need to be studied carefully well beyond the period over which the clinical trials are conducted, and a consistent approach to the collection of data in this regard will be needed as a major collaborative effort.
PubMed: 38553634
DOI: 10.1007/s00223-024-01202-7 -
Journal of Orthopaedic Surgery and... Jul 2023To investigate the patient-related factors that affect the revision rate for the tibia in patients with osteogenesis imperfecta treated with the Peter-Williams nail, and...
OBJECTIVE
To investigate the patient-related factors that affect the revision rate for the tibia in patients with osteogenesis imperfecta treated with the Peter-Williams nail, and to explore the relationship between the risk factors and complications postsurgery.
METHODS
We retrospectively analysed the data of 211 patients (93 females (44.08%) and 118 males (55.92%)) with osteogenesis imperfecta treated with Peter-Williams. The factors affecting surgical revision were analysed by performing binary logistic regression. Then, a total of 211 patients with type III, type I or type IV OI were divided into five groups according to the results of regression. Statistical comparison of these groups was performed to further investigate the relationship between patient-related factors and revision procedures. Statistical comparison was also performed to analyse the relationship between the classification and postoperative complications.
RESULTS
Among the 211 patients who underwent surgery, 40 had type I OI, 109 had type IV OI, and 62 had type III OI. Binary logistic regression revealed that the classification (OR = 3.32, 95% CI 1.06-10.39, P = 0.039) and initial operation age (OR = 0.83, 95% CI 0.76-0.92, P < 0.001) were significantly correlated with revision procedures. In type III patients, the initial operation age was significantly correlated with revision procedures (P < 0.001), and the revision rate was lower in patients aged 9 to12 years (P = 0.001). In type I and IV patients, the initial operation age was not significantly correlated with revision procedures (P = 0.281). Classification had a significant effect on postoperative deformity (P = 0.003).
CONCLUSIONS
The study reported that the age of initial surgery and classification were the influencing factors affecting the revision procedures of tibia in patients with osteogenesis imperfecta treated with the Peter-Williams nail. In patients with type III disease, the revision rate was lower individuals aged 9-12 years old, and a higher incidence of postoperative deformity was observed.
Topics: Male; Female; Humans; Child; Tibia; Osteogenesis Imperfecta; Retrospective Studies; Reoperation; Risk Factors
PubMed: 37496046
DOI: 10.1186/s13018-023-03952-w -
JMIR Research Protocols Jul 2023Osteogenesis imperfecta (OI) is a rare bone fragility disorder associated with muscle weakness. Individuals with OI may therefore benefit from exercise interventions...
BACKGROUND
Osteogenesis imperfecta (OI) is a rare bone fragility disorder associated with muscle weakness. Individuals with OI may therefore benefit from exercise interventions aiming to improve muscle and bone strength. Given the rarity of OI, many patients do not have access to exercise specialists who are familiar with the disorder. As such, telemedicine, the provision of health care through technology to provide care at a distance, may be well suited for this population.
OBJECTIVE
The main objectives are (1) to investigate the feasibility and cost-effectiveness of 2 telemedicine approaches for the delivery of an exercise intervention for youth with OI and (2) to assess the impact of the exercise intervention on muscle function and cardiopulmonary fitness in youth with OI.
METHODS
Patients with OI type I (the mildest form of OI; n=12, aged 12-16 years) from a pediatric orthopedic tertiary hospital will be randomized to receive a 12-week remote exercise intervention in either (1) a supervised group (n=6), monitored every session, or (2) a follow-up group (n=6), receiving monthly progress update appointments. Participants will undergo the following pre- and postintervention evaluations: sit-to-stand test, push-up test, sit-up test, single-legged balance test, and a heel-rise test. Both groups will be given the same 12-week exercise regimen, which includes cardiovascular, resistance, and flexibility training. For each exercise training session involving the supervised group, a kinesiologist will provide instructions to participants through live video sessions using a teleconferencing application. On the other hand, the follow-up group will discuss their progress with the kinesiologist every 4 weeks over a teleconferencing video call. Feasibility will be assessed by recruitment, adherence, and completion rates. A cost-effectiveness analysis of both approaches will be computed. Changes in muscle function and cardiopulmonary fitness will be examined between the 2 groups, pre- and postintervention.
RESULTS
It is anticipated that the supervised group will have higher adherence and completion rates compared to the follow-up group, which may be associated with greater physiological benefits; however, it may not be as cost-effective compared to the follow-up approach.
CONCLUSIONS
By determining the most feasible telemedicine approach, this study may serve as a basis for providing increased access to specialized adjunct therapies for individuals with rare disorders.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/40262.
PubMed: 37399052
DOI: 10.2196/40262 -
Bone May 2024Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is...
INTRODUCTION
Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is bisphosphonate therapy. Previous animal studies have shown that bisphosphonates delay tooth eruption. The aim of this study is to determine whether patients with OI treated with pamidronate and/or zoledronic acid have a delayed eruption age compared to a control group of healthy children.
METHODS
An ambispective longitudinal cohort study evaluating the age of eruption of the first stage mixed dentition in a group of children with OI (n = 37) all treated with intravenous bisphosphonates compared with a group of healthy children (n = 89). Within the study group, the correlation (Pearson correlation test) between the type of medication administered (pamidronate and/or zoledronic acid) and the chronology of tooth eruption is established, as well as the relationship between the amount of cumulative dose received and tooth eruption.
RESULTS
The age of eruption of the study group was significantly delayed compared to the age of eruption of the control group for molars and lateral incisors (p < 0.05). Patients who received higher cumulative doses had a delayed eruption age compared to those with lower cumulative doses (p < 0.05). There is a high positive correlation between age of delayed tooth eruption and Zoledronic acid administration.
CONCLUSION
Patients with OI have a delayed eruption of the 1st stage mixed dentition compared to a control group of healthy children. This delayed eruption is directly related to the cumulative dose of bisphosphonates and the administration of zoledronic ac.
Topics: Child; Animals; Humans; Pamidronate; Zoledronic Acid; Osteogenesis Imperfecta; Tooth Eruption; Bone Density Conservation Agents; Longitudinal Studies; Diphosphonates; Bone Density
PubMed: 38458305
DOI: 10.1016/j.bone.2024.117069 -
Audiology Research Oct 2023There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but...
There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but otosclerosis is one of the most frequent. Similar behavior has been shown in patients affected by osteogenesis imperfecta (OI), a genetic disorder due to a mutation in the genes coding for type I (pro) collagen. In particular, we note that otosclerosis and OI can lead to bone resorption creating pericochlear cavitations in contact with the internal auditory canal (IAC). In this regard, we have collected five cases presenting this characteristic; their audiological data and clinical history were analyzed. This feature can be defined as a potential cause of a third-window effect, because it causes an energy loss during the transmission of sound waves from the oval window (OW) away from the basilar membrane.
PubMed: 37887853
DOI: 10.3390/audiolres13050072 -
Medicina Oral, Patologia Oral Y Cirugia... Jan 2024This study aimed to evaluate facial photoanthropometric parameters in patients with OI.
BACKGROUND
This study aimed to evaluate facial photoanthropometric parameters in patients with OI.
MATERIAL AND METHODS
We selected 20 Brazilian patients diagnosed with OI treated at the Extension Service for Minors in Need of Specialized Treatment of the Dentistry Course at the Federal University of Ceará (Fortaleza, Brazil), of both sexes, without age restriction, and able to understand and sign the informed consent form (ICF). As a control group, 38 non-syndromic Brazilian individuals, categorized as ASA I, able to understand and sign the ICF, matched by sex, age, and Legan and Burstone facial profile were selected. The exclusion criteria were: previous orthodontic treatment, craniofacial trauma and/or surgery, and the presence of any other systemic diseases. Photoanthropometric analysis of the 18 facial parameters proposed by Stengel-Rutkowski et al. (1984), previously established in the literature for craniofacial syndromes, were conducted. A single examiner digitally performed all effective and angular measurements with the CorelDRAWX7® software.
RESULTS
Horizontally shortened ears (p<0.001) but larger in height in relation to the face (p=0.012) were shown to be alterations belonging to individuals with OI.
CONCLUSIONS
OI patients present distinct photoanthropometric parameters inherent in this condition.
Topics: Male; Female; Humans; Face; Osteogenesis Imperfecta; Syndrome; Brazil
PubMed: 37823300
DOI: 10.4317/medoral.26083 -
Frontiers in Endocrinology 2023Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in...
Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%-90% of cases have dominantly inherited heterozygous pathogenic variants located in the and genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in α1 and α2 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the gene and brought new insights into the clinical severity associated with variants localized in "lethal regions". Our results contribute to a better understanding of the clinical and genetic aspects of OI.
Topics: Humans; Collagen Type I; Osteogenesis Imperfecta; Poland; Collagen Type I, alpha 1 Chain; Mutation; High-Throughput Nucleotide Sequencing
PubMed: 37810882
DOI: 10.3389/fendo.2023.1149982 -
Cureus Feb 2024Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by reduced bone density and increased proneness to fractures. It manifests across a...
INTRODUCTION
Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by reduced bone density and increased proneness to fractures. It manifests across a varied clinical spectrum of expressions in children and young adults. It is crucial for children with OI to have a multidisciplinary follow-up, including orthopedics, pediatrics, and physical medicine and rehabilitation. Although exercise may have no effect on the disease itself, it might improve the autonomy, self-esteem, and fitness of these children. Methods: Retrospective cohort analysis of children and young adults aged three or more years old followed-up in a Level III Pediatric Hospital between 1995 and 2020. Demographic and clinical data were obtained from the hospital records and from the caregivers via phone calls. To our knowledge, this is the first national case series published assessing exercise habits in children with this condition.
RESULTS
Among the 21 patients studied, the median age was 14 years, with no gender predominance. Eighteen (86%) practiced regular physical activity, while the remaining three (14%), all of whom were type III OI, were totally dependent. Of the aforementioned 18 children, 12 (67%) considered practicing the same level of physical activity compared to their healthy peers, although most of them needed adaptations. The most reported extracurricular activity was swimming, in 50% of the cases. About 39% engaged in physical activity two times or less per week, and 89% practiced for one hour or less per session.
DISCUSSION
Over the years, it has become clear that physical activity is an important part of OI management. While awareness of the importance of exercise already exists, proper planning, follow-up, and monitoring are essential.
PubMed: 38449982
DOI: 10.7759/cureus.53646 -
Journal of Imaging Oct 2023This study aimed to estimate the utility of the Radiofrequency Echographic Multispectrometry (REMS) approach in the assessment of bone mineral density (BMD) in subjects...
This study aimed to estimate the utility of the Radiofrequency Echographic Multispectrometry (REMS) approach in the assessment of bone mineral density (BMD) in subjects with osteogenesis imperfecta (OI). In 41 subjects (40.5 ± 18.7 years) with OI and in 36 healthy controls, we measured BMD at the lumbar spine (LS-BMD), femoral neck (FN-BMD) and total hip (TH-BMD), employing a dual-energy X-ray absorptiometry tool. Additionally, REMS scans were also performed at the lumbar and femoral sites. The presence and number of reported fractures were assessed in the study population. Patients characterized by a history of fragility fractures represented 84.5% of the study population. OI subjects showed significantly reduced BMD values both at the level of the lumbar spine and the femoral subregions ( < 0.01) compared to healthy controls when performed using both the DXA and the REMS method. Dividing OI patients on the basis of the Sillence classification, no differences were found between the LS-BMD values carried out using the DXA technique between the OI type I group and OI Type III and IV groups. On the contrary, the OI Type III and IV groups presented significantly lower values of both Trabecular Bone Score (TBS) and LS-BMD through REMS with respect to OI type I patients ( < 0.05). Based on the data of this study, it is possible to conclude that even the new REMS assessment, which does not use ionizing radiation, represents an excellent method for studying the bone status in subjects affected by OI.
PubMed: 37888317
DOI: 10.3390/jimaging9100210