Osteogenesis Imperfecta Research Articles

ECG abnormalities in chronic obstructive pulmonary disease exacerbation: can the ECG record still astound us? A prospective study

Introduction/objective Chronic obstructive pulmonary disease (COPD) is a pulmonary disease characterized by persistent respiratory difficulties and impaired airflow. COPD patients have a higher risk for lung infections, like the flu or pneumonia, lung cancer, heart problems, weak muscles, brittle bones, depression, and anxiety. The purpose of this study was to estimate the prevalence of ECG abnormalities in patients with COPD experiencing exacerbations. Patients and methods The research encompassed a cohort of 832 individuals diagnosed with COPD who encountered episodes of exacerbations. Five hundred seventy-five (69.11%) of the included participants were women, and 257 (30.89%) were men. The included participants ranged from 18 to 60 years old. It was ensured that none of the participants had received any treatment for their condition for more than 3 days. Results Based on the level of exacerbation severity, the patient population is categorized into three distinct groups: moderate, comprising 330 (39.66%) individuals; severe, encompassing 406 (48.79%) individuals; and extremely severe, consisting of 96 (11.53%) individuals. During episodes of exacerbation in patients with COPD, the following ECG alterations were observed: a QTc less than 0.40 s in 99.15% of cases, a transitional ECG zone in 74.33% of cases, a P more than 2.5 mm in 45.67% of cases, an axis deviation towards the second quadrant (axis II) in 28% of cases, an incomplete right bundle branch block in 26.32% of cases, and a full right bundle branch block in 25.60% of cases. Conclusion Regardless of prior cardiac pathology, ECG is a low-cost, quick, and dependable modality for detecting ischemic changes in people experiencing a flare-up of COPD.

The genetic landscape of osteogenesis imperfecta: mutational mechanisms and therapeutic targets

Osteogenesis imperfecta is colloquially known as brittle bone disease because it is an inherited disease characterized by a connective tissue disorder that causes decreased bone mass, increased bone fragility and abnormalities in skeletal structure. This disease is caused by a mutation in the type I collagen genes, specifically COL1A1 and COL1A2, resulting in a variety of clinical manifestations ranging from mild to lethal. The impact on the quality of life of patients with OI can be complicated, which is why they need multidisciplinary management strategies including orthopedic care, physical therapy, pain management and surgical interventions.

National Trends in Inpatient Hospital Outcomes of Children with Osteogenesis Imperfecta and the Importance of Extraskeletal Manifestations: A Kids’ Inpatient Database Study

ObjectiveTo investigate the extent of extra-skeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI). Study designThis 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. ResultsThere 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. ConclusionWe 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.

Anesthetic Management of Femur Fracture in a Pediatric Patient with Osteogenesis Imperfecta

Anesthetic Management of Femur Fracture in a Pediatric Patient with Osteogenesis Imperfecta

Clinical spectrum of rare bone fragility disorders and response to bisphosphonate treatment: a retrospective study.

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 (<3rd 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.

Surgical treatment of scoliosis in patients with osteogenesis imperfecta: a single institution case series.

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. 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. 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. 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.

Zoledronic acid: challenges and pitfalls amid rehabilitation in primary osteoporosis and beyond

Zoledronate (or zoledronic acid) represents a standard (guideline-based) approach in the area of anti-resorptive medication (namely, an annual 15-minute perfusion of 5 mg for os-teoporosis treatment), while the same drug (with doses/regimes variations) is used for other bone metabolic conditions such as Paget’s disease of the bone or skeleton metastasis originating from different cancers. The objective of this narrative review was to highlight the most recent published data with respect to zoledronic acid use as part of the complex clinical management amid primary osteoporosis in addition to other osteo-metabolic clin-ical entities. This was a research based on exploring PubMed database with respect to the search words “zoledronic acid” and “primary osteoporosis”. We included highly relevant (from the clinical perspective), English-published, full-length articles that have been re-cently published (between January 2023 and March 2024). From 249 results, 31 articles met the inclusion timeline criteria across the 15-month analysis and the final results were based on data provided from 16 articles. Important insights concern not only the zoledronic acid administration, the efficacy and the safety profile, but, also, an extension on daily indications with concern to diabetic bone disease, liver osteodystrophy, osteogen-esis imperfecta or Paget’s disease of the bone. Keywords: osteoporosis, rehabilitation, zoledronic acid, DXA, hypercalcemia, bone, surgery, prosthesis, Paget’s disease of the bone, liver osteodystrophy

Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy and their association with age and estimated glomerular filtration rate (eGFR). This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over 1 year. Patients' clinical data were collected. The levels of BTMs and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decreased levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.

Low muscle density in children with osteogenesis imperfecta using opportunistic low-dose chest CT: a case-control study

BackgroundThe aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children.MethodsThis single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests.Results20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm2, p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm2, p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively).ConclusionsChildren with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children.

Current situation of osteogenesis imperfecta in Spain: results from a Delphi study

BackgroundOsteogenesis 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.ResultsThe 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.ConclusionsThis 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.

Nutritional Behavior of Patients with Bone Diseases: A Cross-Sectional Study from Austria.

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. 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). 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, p = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption (p = 0.016), fruit/vegetable juice consumption (p = 0.034), portions of fish per week (p = 0.044), high-fat meals per week (p = 0.015) and consumption of salty snacks (p = 0.001). 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.

Prevalence, number of fractures, and hospital characteristics among the pediatric population with osteogenesis imperfecta: results from the nationwide registry of Türkiye.

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. 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. 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. 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.

PCR124 Burden of Fracture and Fracture Management Among Individuals with Osteogenesis Imperfecta: Results from a Survey of Adults and Caregivers

PCR124 Burden of Fracture and Fracture Management Among Individuals with Osteogenesis Imperfecta: Results from a Survey of Adults and Caregivers

EE516 Estimating the Benefits of Reduced Fracture Incidence for Patients Living with Osteogenesis Imperfecta and for Healthcare Payers

EE516 Estimating the Benefits of Reduced Fracture Incidence for Patients Living with Osteogenesis Imperfecta and for Healthcare Payers

EE202 Conceptualization and Validation of a Health Economic Model for Osteogenesis Imperfecta

EE202 Conceptualization and Validation of a Health Economic Model for Osteogenesis Imperfecta

EPH65 Burden of Illness of Osteogenesis Imperfecta in Ontario, Canada

EPH65 Burden of Illness of Osteogenesis Imperfecta in Ontario, Canada

Unraveling the Link of Altered TGFβ Signaling with Scoliotic Vertebral Malformations in Osteogenesis Imperfecta: A Comprehensive 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.

Sclerostin antibody enhances implant osseointegration in bone with Col1a1 mutation

We evaluated the potential of sclerostin antibody (SclAb) therapy to enhance osseointegration of dental and orthopaedic implants in a mouse model (Brtl/+) mimicking moderate to severe Osteogenesis Imperfecta (OI). To address the challenges in achieving stable implant integration in compromised bone conditions, our aim was to determine the effectiveness of sclerostin antibody (SclAb) at improving bone-to-implant contact and implant fixation strength. Utilizing a combination of micro-computed tomography, mechanical push-in testing, immunohistochemistry, and Western blot analysis, we observed that SclAb treatment significantly enhances bone volume fraction (BV/TV) and bone-implant contact (BIC) in Brtl/+ mice, suggesting a normalization of bone structure toward WT levels. Despite variations in implant survival rates between the maxilla and tibia, SclAb treatment consistently improved implant stability and resistance to mechanical forces, highlighting its potential to overcome the inherent challenges of OI in dental and orthopaedic implant integration. These results suggest that SclAb could be a valuable therapeutic approach for enhancing implant success in compromised bone conditions.

The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in patients with OI type V. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with an increase in the skeletal progenitor cell population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 had decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupted early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.

Resilience and coping: a qualitative analysis of cognitive and behavioral factors in adults with osteogenesis Imperfecta

Purpose The aim of this qualitative study was to investigate resilience among adults with Osteogenesis Imperfecta (OI). Materials and methods Semi-structured interviews were conducted with 15 adults with OI. Transcripts were coded and subsequently abstracted, yielding themes specific to resilience and coping. Interview guides covered broad topics including pain challenges specific to OI, mental health issues related to OI, and priorities for future interventions for individuals with OI. Results Participants described resilience in the context of OI as the ability to grow from adversity, adapt to challenges resulting from OI-related injuries, and find identities apart from their condition. Psychological coping strategies included acceptance, self-efficacy, cognitive reframing, perspective-taking, and positivity. Behavioral factors that helped participants develop resilience included developing new skills, pursuing meaningful goals, practicing spirituality, and seeking external resources such as psychotherapy, education, and connection with community. Conclusion Having identified how adults with OI define resilience and the strategies they use to cope, we can now develop interventions and guide healthcare providers in improving psychological wellbeing in this population.