-
The Journal of Pediatrics Jun 2024To investigate the extent of extra-skeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI).
National Trends in Inpatient Hospital Outcomes of Children with Osteogenesis Imperfecta and the Importance of Extra-skeletal Manifestations: A Kids' Inpatient Database Study.
OBJECTIVE
To investigate the extent of extra-skeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI).
STUDY DESIGN
This cross-sectional study utilized the Kids' Inpatient Database (KID) as part of the Healthcare Cost and Utilization Project (HCUP) to investigate inpatient hospital outcomes and management in patients with OI from 1997 through 2016. Data regarding hospital characteristics, cost of treatment, inpatient outcomes, and procedures were collected and analyzed.
RESULTS
There were 7,291 admissions that listed OI as a diagnosis in the KID database from 1997 through 2016. Unexpectedly, over one third of all admissions in these children with OI presented with an extra-skeletal manifestation. The rate of major complications was 3.85%. The rate of minor complications was 19.4%, most commonly respiratory problems. Mortality rate was 18.2 % in the neonatal period and 1.0% in all other admissions. Total charges of hospital stay increased over the years.
CONCLUSION
We identified a striking prevalence of extra-skeletal manifestations in OI along with inpatient outcomes and complications associated with OI, of which respiratory complications were predominant. We observed a significant financial burden for patients with OI and identified additional risks for financial crisis, in addition to disparities in care identified among socioeconomic groups. These data contribute to a more holistic understanding of OI from diagnosis to management.
PubMed: 38945443
DOI: 10.1016/j.jpeds.2024.114174 -
Calcified Tissue International Jun 2024In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the... (Review)
Review
In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the new Dyadic Nosology for Genetic Disorders of the Skeleton. Some 770 entities were delineated associated with 552 genes. From these entities, over 40 genes resulting in distinct forms of Osteogenesis Imperfecta (OI) and Bone Fragility and/or Familial Osteoporosis were identified. To assist clinicians and lay stake holders and bring the considerable body of knowledge of the matrix biology and genomics to people with OI as well as to clinicians and scientists, a dyadic nosology has been recommended. This combines a genomic co-descriptor with a phenotypic naming based on the widely used Sillence nosology for the OI syndromes and the many other syndromes characterized in part by bone fragility.This review recapitulates and explains the evolution from the simple Congenita and Tarda subclassification of OI in the 1970 nosology, which was replaced by the Sillence types I-IV nosology which was again replaced in 2009 with 5 clinical groups, type 1 to 5. Qualitative and quantitative defects in type I collagen polypeptides were postulated to account for the genetic heterogeneity in OI for nearly 30 years, when OI type 5, a non-collagen disorder was recognized. Advances in matrix biology and genomics since that time have confirmed a surprising complexity both in transcriptional as well as post-translational mechanisms of collagens as well as in the many mechanisms of calcified tissue homeostasis and integrity.
PubMed: 38942908
DOI: 10.1007/s00223-024-01248-7 -
Nutrients Jun 2024A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD)....
BACKGROUND
A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was to evaluate the nutritional behavior of patients with RBD.
METHODS
This single-center, cross-sectional, questionnaire-based study assessed the nutritional behavior of RBD patients (X-linked hypophosphatemia (XLH), osteogenesis imperfecta (OI), hypophosphatasia (HPP)), osteoporosis (OPO) patients and healthy controls (CTRL). The nutritional questionnaire comprised 25 questions from seven nutritional areas. The associations between socioeconomic factors and BMI were assessed by age-adjusted univariate analysis of covariance (ANCOVA).
RESULTS
Fifty patients with RBD (17 OI, 17 HPP, 16 XLH; mean age of 48.8 ± 15.9, 26.0% male, mean BMI 26.2 ± 5.6), 51 with OPO (mean age 66.6 ± 10.0, 9.8% male, mean BMI 24.2 ± 3.9) and 52 CTRL (mean age 50.8 ± 16.3, 26.9% male, mean BMI 26.4 ± 4.7) participated. Twenty-six (52.0%) RBD, 17 (33.4%) OPO and 24 (46.1%) CTRL were overweight or obese according to BMI. Only a minority of RBD, OPO and CTRL had a daily intake of at least three portions of milk or milk products (17.3% RBD, 15.6% OPO, 11.6% CTRL, = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption ( = 0.016), fruit/vegetable juice consumption ( = 0.034), portions of fish per week ( = 0.044), high-fat meals per week ( = 0.015) and consumption of salty snacks ( = 0.001).
CONCLUSION
Nutritional counseling, controlling BMI and ensuring sufficient calcium and protein intake are crucial in patients with osteoporosis as well as in rare bone diseases. Vitamin D does not appear to be sufficiently supplied by the diet, and therefore supplementation should be considered in patients with bone diseases.
Topics: Humans; Cross-Sectional Studies; Male; Female; Middle Aged; Austria; Adult; Aged; Bone Diseases; Surveys and Questionnaires; Body Mass Index; Osteoporosis; Feeding Behavior; Nutritional Status; Diet
PubMed: 38931274
DOI: 10.3390/nu16121920 -
Journal of Clinical Medicine Jun 2024Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen... (Review)
Review
Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen fibers. Its predominant skeletal complication is scoliosis, impacting 25 to 80% of OI patients. Vertebral deformities of the scoliotic curves in OI include a variety of malformations such as codfish, wedged-shaped vertebrae or platyspondyly, craniocervical junction abnormalities, and lumbosacral spondylolysis and spondylolisthesis. Although the precise pathophysiology of these spinal deformities remains unclear, anomalies in bone metabolism have been implicated in the progression of scoliotic curves. Bone Mineral Density (BMD) measurements have demonstrated a significant reduction in the Z-score, indicating osteoporosis and a correlation with the advancement of scoliosis. Factors such as increased mechanical strains, joint hypermobility, lower leg length discrepancy, pelvic obliquity, spinal ligament hypermobility, or vertebrae microfractures may also contribute to the severity of scoliosis. Histological vertebral analysis has confirmed that changes in trabecular microarchitecture, associated with inadequate bone turnover, indicate generalized bone metabolic defects in OI. At the molecular level, the upregulation of Transforming Growth factor-β (TGFβ) signaling in OI can lead to disturbed bone turnover and changes in muscle mass and strength. Understanding the relationship between spinal clinical features and molecular pathways could unveil TGFβ -related molecular targets, paving the way for novel therapeutic approaches in OI.
PubMed: 38930011
DOI: 10.3390/jcm13123484 -
Genes May 2024Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I),...
Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. This study analyzed the clinical-genetic characteristics of patients with these conditions, focusing on both known and newly identified variants. We examined data from 15 patients, presenting symptoms of OI and joint contractures. Diagnostic methods included genealogical analysis, clinical assessments, radiography, whole exome sequencing, and direct automated Sanger sequencing. We diagnosed 15 patients with phenotypes due to biallelic variants-4 with OI Type XI, 10 with BS I, and 1 with the AG-like phenotype-demonstrating polymorphism in disease severity. Ten pathogenic variants were identified, including three novel ones, c.1373C>T (p.Pro458Leu), c.21del (p.Pro7fs), and c.831_832insCG (p.Gly278Argfs), and a recurrent variant, c.831dup (p.Gly278Argfs). Variant c.1490G>A (p.Trp497Ter) was found in two unrelated patients, causing OI XI in one and BS I in the other. Additionally, two unrelated patients with BS I and epidermolysis bullosa shared identical homozygous and variants. This observation illustrates the diversity of -related pathology and the importance of considering the full spectrum of phenotypes in clinical diagnostics.
Topics: Humans; Tacrolimus Binding Proteins; Male; Female; Arthrogryposis; Phenotype; Osteogenesis Imperfecta; Child; Child, Preschool; Pedigree; Exome Sequencing; Adolescent; Mutation; Infant; Adult; Nervous System Malformations
PubMed: 38927610
DOI: 10.3390/genes15060674 -
European Journal of Human Genetics :... Jun 2024Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by brittle bones. Though genetic mutations in COL1A1 and...
Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by brittle bones. Though genetic mutations in COL1A1 and COL1A2 account for approximately 85-90% of OI cases, there are now more than twenty genes described, responsible for rare forms of OI. Treatment is based on the use of bisphosphonates and though it is well established that they increase lumbar spine (LS) bone mineral density (BMD), the clinical impact on fracture reduction is still debated.In this study, we investigated the clinical characteristics of 38 patients with a bone fragility disorder that had variants in non-COL1A1/COL1A2 genes in order to study genotype-phenotype correlations, as the natural history of these rare forms is still not well known. We then studied the usefulness of bisphosphonate treatment by evaluating the effects on LS BMD, annual non-vertebral fracture rate, bone turnover markers and height. This study enabled us to better define the natural history of patients with non-COL1 pathogenic variants. Patients with CRTAP and TMEM38B variants consistently had a prenatal presentation with a short (<3 p) and bowed femur. Importantly, this prenatal involvement does not predict the postnatal severity of the disease. Regarding treatment by bisphosphonates, all patients showed a significant increase in LS BMD while treated and this increase was dependent on the dose received. The increase in LS BMD also translated in a reduction of fracture rate during treatment. Finally, our study showed that the earlier bisphosphonates are initiated, the greater the fracture rate is reduced.
PubMed: 38926541
DOI: 10.1038/s41431-024-01645-4 -
Cureus May 2024Osteogenesis imperfecta (OI) is a rare inherited skeletal disease, characterized by bone fragility and low bone density. There are several types of OI, varying in...
Osteogenesis imperfecta (OI) is a rare inherited skeletal disease, characterized by bone fragility and low bone density. There are several types of OI, varying in severity from benign to severe. We report a case of type II OI, which is a lethal form according to the Sillence classification. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. The genetic analysis was done along with genetic counseling. Death occurred on day nine of life due to respiratory failure secondary to pulmonary hypoplasia.
PubMed: 38910652
DOI: 10.7759/cureus.60945 -
Musculoskeletal Surgery Jun 2024Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by skeletal deformities, bone fragility, and spinal complications. Various studies' insights...
BACKGROUND
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by skeletal deformities, bone fragility, and spinal complications. Various studies' insights underscored the impact of scoliosis on pulmonary function, positive outcomes with spinal fusion, and improved functional abilities post-surgery. However, partial loss of correction remains inevitable.
METHODS
This study examines six surgically treated OI patients with scoliosis. Surgical intervention using a posterior approach with pedicle screws and hooks aimed to correct spinal deformities. Preoperative, postoperative, and follow-up radiological assessments were conducted, revealing significant reductions in scoliotic angles post-surgery.
RESULTS
Complications included infections and proximal junctional kyphosis requiring revision surgeries. Despite the challenges posed by poor bone quality and implant stability, no implant failures occurred in this series. Ponte osteotomies at the apex of deformity aided in corrective maneuvers.
CONCLUSION
Surgical treatment of scoliosis in patients affected by OI is challenging and may be associated with perioperative and postoperative complications. Ponte osteotomy may improve the correction and reduce necessary force at the time of correction.
PubMed: 38907836
DOI: 10.1007/s12306-024-00842-0 -
Journal of Pediatric Orthopedics. Part B Jun 2024Osteogenesis imperfecta is a rare connective tissue disorder with an estimated number of 4-20 cases per 100 000 inhabitants. Although the prevalence differs among...
Prevalence, number of fractures, and hospital characteristics among the pediatric population with osteogenesis imperfecta: results from the nationwide registry of Türkiye.
OBJECTIVE
Osteogenesis imperfecta is a rare connective tissue disorder with an estimated number of 4-20 cases per 100 000 inhabitants. Although the prevalence differs among regions, there are only a few number of national registry studies published previously. The aim of this study was to determine the prevalence of osteogenesis imperfecta among the pediatric age group in Türkiye, together with the patient and hospital characteristics.
METHODS
Via the e-health database of the Turkish Ministry of Health, we collected and retrospectively evaluated the medical records of the patients who were under 18 years of age with the diagnosis of osteogenesis imperfecta between 2016 and 2022. Total number of fractures, treatment modalities, and the hospital characteristics were also recorded. Two thousand seven hundred forty patients were extracted with a mean age of 9.77 ± 4.81 years.
RESULTS
The prevalence of osteogenesis imperfecta in Türkiye among the pediatric population was calculated as 11.6 per 100 000 individuals. The median annual incidence was 31.5 per 100 000 live births between 2016 and 2022. There were 17.4 hospital admissions per patient per year. The mean age at the time of in-hospital mortality was 4.08 ± 5.03 years. The fracture rate per patient per year was 0.56 and conservative treatment was the most commonly preferred modality for all ages.
CONCLUSION
This is the first registry-based nationwide study of osteogenesis imperfecta patients in Türkiye, providing important characteristics of the disease. Together with the help of the ongoing development of national health database systems, precision in patient identification would yield substantial benefits in terms of management of osteogenesis imperfecta.
PubMed: 38900105
DOI: 10.1097/BPB.0000000000001192 -
Orphanet Journal of Rare Diseases Jun 2024Osteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and...
BACKGROUND
Osteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and extra-skeletal symptoms that results in an impairment of health-related quality of life of OI patients. Since published studies on OI in Spain are limited, this study aimed to determine the epidemiology, assessed the disease burden, management and unmet needs of OI patients in Spain. Thirty-four experts in the management of patients with osteogenesis imperfecta completed two rounds of online consultation and reported real-life experience and data from Spanish hospitals. Delphi study questionnaires were based on literature review. A working group of nationally recognized clinical experts supported the development of the study questionnaires and the final validation of results.
RESULTS
The estimated prevalence of patients diagnosed with OI in Spain is 0.56:10,000 inhabitants (95%CI: 0.54-0.59), which represents that, approximately, 2,669 OI patients are currently managed in Spanish hospitals. It is estimated that approximately 269 new patients would be diagnosed with OI each year in Spain, representing an estimated incidence of 0.06 (95%CI: 0.05-0.06) per 10,000 inhabitants per year. Clinical management of OI in Spain is performed by a range of medical specialists; however, multidisciplinary care is not fully implemented. The absence of an approved curative treatment or a treatment to reduce the clinical features of the disease remains the main unmet need.
CONCLUSIONS
This study provides a snapshot of the current situation of patients with OI in Spain reported by clinical experts. The results provide an estimation of the epidemiology of the disease, and complement the available evidence on disease burden, clinical management, and unmet needs of these patients in Spain.
Topics: Osteogenesis Imperfecta; Humans; Spain; Delphi Technique; Surveys and Questionnaires; Quality of Life; Female; Male; Prevalence
PubMed: 38890698
DOI: 10.1186/s13023-024-03248-0