Home care needs assessment among caregivers of children and adolescents with osteogenesis imperfecta: a cross-sectional study.

BACKGROUND: Children and adolescents with complex medical issues need home care services; however, few studies have provided insight into the unmet home care needs of the families of patients with osteogenesis imperfecta (OI). In this study, we aimed to assess the home care needs of caregivers of children and adolescents with OI and the associated factors. METHODS: A self-administered questionnaire was administered online to 142 caregivers of patients with OI aged 3-17 years between May and October 2022 from 25 provinces in China. The questionnaire comprised 15 questions on demographic variables and 14 questions on home care needs. Chi-square analysis was used to compare group differences for categorical variables. Multivariate binary logistic regression analysis was conducted to examine predictors of caregivers' home care needs. RESULTS: The study findings indicated that 81.5% of caregivers had high home care needs. The three leading types of home care needs were helping the child carry out physical fitness recovery exercises at home (72.5%), understanding precautions regarding treatment drugs (72.5%), and relieving the child's pain (70.4%). OI patients' poor self-care ability (adjusted odds ratio = 5.9, 95% confidence interval = 1.8-19.0) was related to caregivers' high level of home care needs. CONCLUSIONS: The findings of this study suggest that future scientific research and nursing guidance should focus on OI patients' physical training, medication management, pain relief, fracture prevention, and treatment. In addition, caregivers of patients with poor self-care ability should receive special attention in the development of interventions. This study can help with addressing the unmet home care needs of caregivers of children and adolescents with OI. It is vital to develop a personalized intervention plan based on patients' self-care ability.

Identification of a family with van der Hoeve's syndrome harboring a novel COL1A1 mutation and generation of patient-derived iPSC lines and CRISPR/Cas9-corrected isogenic iPSCs.

Van der Hoeve's syndrome, also known as osteogenesis imperfecta (OI), is a genetic connective tissue disorder characterized by fragile, fracture-prone bone and hearing loss. The disease is caused by a gene mutation in one of the two type I collagen genes COL1A1 or COL1A2. In this study, we identified a novel frameshift mutation of the COL1A1 gene (c.1607delG) in a family with OI using whole-exome sequencing, bioinformatics analysis and Sanger sequencing. This mutation may lead to the deletion of a portion of exon 23 and the generation of a premature stop codon in the COL1A1 gene. To further investigate the impact of this mutation, we established two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of OI patients carrying a novel mutation in the COL1A1 gene. Osteoblasts (OB) derived from OI-iPSCs exhibited reduced production of type I collagen and diminished ability to differentiate into osteoblasts. Using a CRISPR-based homology-directed repair strategy, we corrected the OI disease-causing COL1A1 novel mutations in iPSCs generated from an affected individual. Our results demonstrated that the diminished expression of type I collagen and osteogenic potential were enhanced in OB induced from corrected OI-iPSCs compared to those from OI-iPSCs. Overall, our results provide new insights into the genetic basis of Van der Hoeve's syndrome and highlight the potential of iPSC technology for disease modeling and therapeutic development.

Access to care among patients with osteogenesis imperfecta during the COVID-19 pandemic.

In a cross-sectional study assessing the experiences of individuals with osteogenesis imperfecta accessing care during the COVID-19 pandemic, participants reported high rates of delays in accessing medical care and high utilization of telehealth. Considering the needs of individuals with complex medical conditions is important when improving access to care. PURPOSE: Individuals with osteogenesis imperfecta (OI) often have complex care needs requiring that they see a variety of specialists. The onset of the COVID-19 pandemic in March 2020 led to delays in medical care for many health conditions. The goal of this study was to describe the experiences of individuals with OI accessing medical care during this time. METHODS: Responses to an electronic survey distributed via the OI Foundation mailing list were collected from August 2020 until February 2021. Participants were instructed to compare their experiences in the months since the start of the pandemic with their experiences prior to this date. Data were analyzed using descriptive statistics and were compared across demographic groups using logistic regression and chi-squared tests. RESULTS: Surveys were completed by 110 participants. Most participants (72%) reported experiencing delays in accessing at least one care provider. The majority of participants reported less or similar amounts of bone pain (74.3%) and less or the same rate of fracture (88.6%) as before the start of the pandemic. CONCLUSION: While most study participants experienced delays in care, they did not report an increase in symptoms associated with OI. They also frequently utilized telehealth as a tool to see their providers. Future research should focus on the impact of changes in telehealth legislation on patients' ability to access care. As methods for care delivery evolve, the needs of people with OI and other rare diseases should be considered and prioritized.

Life span care for patients with skeletal dysplasia: A roadmap.

Patients with skeletal dysplasias usually experience health related problems in different parts and systems of the body. Therefore, they face challenges in multiple domains of functioning and health. To address these different domains, interdisciplinary care should be the standard for these patients. The basic algorithm of interdisciplinary care can be similar for patients with different skeletal dysplasias, as many of the problems and needs are generic within different age groups. With increased age the domains in which patients with skeletal dysplasia face challenges will change and the focus and frequency of the interdisciplinary care should change accordingly. Thorough understanding of the specific characteristics of different skeletal dysplasias is required to create an individualized efficient interdisciplinary screening and care program. This paper presents the current structure and rationale of the interdisciplinary screening and care program of the skeletal dysplasia expert center of the University Medical Center Utrecht in the Netherlands. It is presented here, tailored to osteogenesis imperfecta, but the structure of the program is generic for all skeletal dysplasias.

Early Life Management of Osteogenesis Imperfecta.

PURPOSE OF REVIEW: This review aims to provide a review of the multidisciplinary management of infants with osteogenesis imperfecta (OI) during the first year of life, focusing on those with severe disease. The authors draw on published literature and direct experience of working in a large paediatric centre specialising in the management of rare bone disease. RECENT FINDINGS: Whilst understanding of the pathophysiology of OI has grown over the past decade, the evidence base for management of infants remains limited. There has been a greater recognition of certain subjects of concern including pain management, cervical spine deformity, and neurocognitive development. Both international consensus guidelines on rehabilitation and disease-specific growth charts have been welcomed by clinical teams. The early involvement of multidisciplinary specialist care is critical in ensuring optimal care for the infant with severe OI. A long-term perspective which focuses on the axial, craniofacial, and peripheral skeleton as well as on development more generally provides a framework which can guide the management of infants with severe OI.

Transition from Pediatric to Adult Health Care in Osteogenesis Imperfecta.

PURPOSE: Here, we review issues regarding the transition from pediatric to adult-focused health care for individuals with osteogenesis imperfecta (OI). RECENT FINDINGS: The clinical consequences of OI change during the lifespan. Fracture rates are lower in adults than in children with OI, whereas other manifestations are typically becoming more prominent in adults. The evidence base for the transition to adult health care in OI is thin, as the literature on the topic is limited to qualitative investigations on a small number of participants. A few tools to help with transition, such as a program to improve self-management skills, have been developed. The transition process varies markedly between health care systems, which makes generalizations difficult. However, a better definition of follow-up requirements and care of adults with OI might be helpful for the transition from pediatric to adult health care.

CRISPR/Cas9 correction of a dominant cis-double-variant in COL1A1 isolated from a patient with osteogenesis imperfecta increases the osteogenic capacity of induced pluripotent stem cells.

Osteogenesis imperfecta (OI) is a hereditary skeletal disorder that is mainly caused by variants in COL1A1/2. So far, no specific treatment has been developed to correct its underlying etiology. We aimed to gain a better understanding of the pathological mechanisms of OI and develop gene therapies to correct OI-causing variants. A de novel cis-double-variant c.[175C>T; 187T>A] in COL1A1 was identified from a 5-year-old OI patient by whole-exome sequencing (WES). Three peptide nucleic acids (PNAs) were designed and then transfected patient-derived fibroblasts. PNA2 affected the translational strand and induced an optimal interfering effect at 0.25µM concentration, proved by Sanger sequencing, qPCR, Western blot, and immunostaining. Additionally, induced pluripotent stem cells (iPSCs) were cultured from patient-derived fibroblasts. Clones of iPSCs with c.187T>A variant and those with both variants largely restored their osteogenic capacities after CRISPR/Cas9 gene editing, which corrected the variants. Importantly, correcting c.187T>A variant alone in CRISPR-edited iPSCs was sufficient to alleviate OI phenotypes, as indicated by increased levels of COL1A1, COL1A2, ALP mRNAs, and COL1A1 protein. Our findings suggest that c.187T>A is the dominant variant of cis-double-variant in COL1A1 that led to OI, and PNA interference and CRISPR/Cas9 gene editing may be new therapeutic tools for OI treatment. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Multimodal Pain Management of Children Diagnosed with Osteogenesis Imperfecta: An Integrative Literature Review.

OBJECTIVES: The objective of this literature review was to evaluate multimodal therapies and interventions that help prevent progression and manage pain in children with OI. DESIGN: A systematic review of literature utilizing PRISMA guidelines. DATA SOURCES: The Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, PubMed, PsycINFO, UpToDate, and ProQuest Nursing & Allied Health Source. REVIEW/ANALYSIS METHODS: Existing literature on pain management in pediatric patients diagnosed with OI was reviewed and appraised. Fifteen studies met the criteria for review. RESULTS: Results indicated that therapies addressing pain management are most effective when they use a multimodal approach that promotes bone strength, psychological support, reduces the risk of fractures, increases bone stability, and maintains physiological function. Four multimodal treatments for pain management in children with OI were identified including bisphosphonate therapy, surgical intervention, physical therapy, and psychosocial support. CONCLUSIONS: Developing a finite understanding of the utilization of multimodal therapies to manage and treat pain can assist in engineering treatments that improve the quality of life for children diagnosed with OI.

Treatments for hearing loss in osteogenesis imperfecta: a systematic review and meta-analysis on their efficacy.

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.

The prevalence of musculoskeletal pain and therapy needs in adults with Osteogenesis Imperfecta (OI) a cross-sectional analysis.

BACKGROUND: Osteogenesis Imperfecta affects approximately 1 in every 10,000 people. Musculoskeletal disorders and pain are common in adults with Osteogenesis Imperfecta, but specific knowledge of the problems people have is lacking. Access to therapy services for adults with Osteogenesis Imperfecta is variable. We designed this analysis to better understand the musculoskeletal disorders and consequent therapy needs for adults with Osteogenesis Imperfecta.  METHODS: This study was a cross-sectional analysis of outpatients with Osteogenesis Imperfecta. Adults attending a newly established multidisciplinary clinic at a tertiary centre in 2019 were included. A highly specialist physiotherapist worked within the clinic to offer therapy input if required and to refer patients to appropriate therapy as needed. People over the age of 18 were included if they had a diagnosis of Osteogenesis Imperfecta. Data were collected over a five month period using routinely collected clinical information and patient reported outcomes. RESULTS: Over five months 50 patients attended the clinic. Musculoskeletal pain was a significant feature reported by 84% of patients. Over 50% of patients reported persistent pain for longer than one year duration and the most common site of pain was in the spine (46%). No difference in pain between types of OI and age. Forty five per cent (n = 19) of patients reported moderate to severe problems with mobility on the EQ-5D with over half reporting problems with self-care and ability to carry out usual activities. Over 50% of patients in clinic also reported anxiety (EQ-5D). During the consultation 70% of patients received therapy input which was either advice in clinic or an onward referral to the appropriate service. The referral rate to specialist out-patient rehabilitation services at a tertiary centre was 30%. CONCLUSIONS: This analysis highlights the high prevalence of MSK pain in adults with OI and the effect on physical function and emotional wellbeing. This study demonstrates the diverse needs of the adult Osteogenesis Imperfecta population and the need for suitable multidisciplinary therapy services.

Curative Cell and Gene Therapy for Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) describes a series of genetic bone fragility disorders that can have a substantive impact on patient quality of life. The multidisciplinary approach to management of children and adults with OI primarily involves the administration of antiresorptive medication, allied health (physiotherapy and occupational therapy), and orthopedic surgery. However, advances in gene editing technology and gene therapy vectors bring with them the promise of gene-targeted interventions to provide an enduring or perhaps permanent cure for OI. This review describes emergent technologies for cell- and gene-targeted therapies, major hurdles to their implementation, and the prospects of their future success with a focus on bone disorders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effect of physiotherapy rehabilitation on osteogenesis imperfecta with a midshaft tibial fracture in the 11-year-old patient: a case report.

Osteogenesis imperfecta (OI), a brittle bone disease is a rare genetic condition characterised by skeletal anomalies that results in higher bone fragility, reduced bone mass, deformity, and other connective-tissue signs in which the body is unable to form healthy bones. This case report presents a case of an 11-year-old male kid who visited our hospital with a complaint of pain and deformity in his left leg. After investigations, he was diagnosed with osteogenesis imperfecta with a midshaft tibial fracture of the left leg. Physical therapy rehabilitation was started and plays one of the important roles in the management of this condition along with medical and orthopedic management. Physical therapy involves strengthening exercises, stretching exercises, bracing, functional activities, gait training, etc. This case study highlighted that physical therapy rehabilitation along with multidisciplinary care; can help the patient with pain management and functional independence which enhances the patient's strength, endurance, prevents deformity, and improves the patient's quality of life.

Patient-reported experience of clinical care of osteogenesis imperfecta (OI) during the COVID-19 pandemic.

Background: Research on the effects of the COVID-19 pandemic on people with rare diseases is limited. Few studies compare healthcare throughout the progression of the ongoing pandemic. Aims: To assess the impact of the pandemic on individuals with osteogenesis imperfecta across two consecutive years, understand what challenges were encountered, and analyse the experience of remote consultation. Methods: An initial survey was distributed following the first lockdown in August 2020, and a second survey in April 2021. The surveys explored four themes- effects on therapy, alternatives to consultation, effect on mental health, and perceived risks of COVID-19. Results: In the 2020 survey, of the 110 respondents, 69 (63%) had at least one appointment delayed due to the lockdown, compared with 89 of the 124 respondents (72%) in 2021. Of the 110 respondents in 2020, 57 (52%) had a remote consultation, increasing to 92 of 124 (74%) in the follow-up survey. In the 2020 survey 63 of 91 respondents (69%) expressed anxiety due to lockdown, compared with 76 of 124 (61%) in 2021. The percentage of total respondents expressing a preference for remote consultation was 48% in 2020, increasing to 71% in 2021. Conclusions: The pandemic has had widespread effects on the mental and physical health of those with OI. These effects, alongside appointment delays, have increased as the pandemic progresses. Encouragingly, the increasing preference for remote consultation may indicate that this could be a viable long-lasting alternative to face-to-face appointments, especially for patients who previously traveled vast distances for specialist care.

Efectividad de la fisioterapia en el desarrollo motor de niños con osteogénesis imperfecta: una revisión sistemática / Effectiveness of physiotherapy in the motor development of children with osteogenesis imperfecta: A systematic review

Antecedentes y objetivo La osteogénesis imperfecta es una enfermedad rara cuya característica principal es la presencia de fragilidad ósea. Además, estos pacientes presentan bajo tono muscular, laxitud ligamentosa, esclerótica azul, retraso en el crecimiento, problemas dentales y alteraciones en el desarrollo motor. El objetivo del presente estudio es analizar la evidencia existente sobre el efecto de la fisioterapia en el desarrollo de la motricidad gruesa y fina en niños con osteogénesis imperfecta. Material y métodos Revisión sistemática cualitativa de ensayos clínicos y estudios observacionales sobre el tratamiento fisioterapéutico en niños con osteogénesis imperfecta publicados en revistas científicas. Se realizó la búsqueda bibliográfica en las bases informatizadas Medline, BASE, Cochrane, EBSCO, SCOPUS y Web of Science. Resultados Fueron identificados 102 artículos en las bases de datos informatizadas. Tras cribar los artículos con los criterios de inclusión establecidos en el presente trabajo y la eliminación de los duplicados fueron incluidos 4 artículos en este estudio. En estos 4 artículos se evaluó el riesgo de sesgo según el manual de revisiones sistemáticas de Cochrane. Se observaron mejoras en las variables fuerza muscular, función motora, fatiga, marcha, resistencia aeróbica y densidad ósea. Los resultados entre estudios son difíciles de comparar debido a su heterogeneidad. Conclusiones La fisioterapia puede mejorar la motricidad gruesa en niños con osteogénesis imperfecta. Es necesario un mayor número de estudios con una mejor calidad metodológica para confirmar con mayor evidencia los resultados (AU)

Background and objective Osteogenesis imperfecta is a rare disease with a low prevalence. It is characterized by a bone fragility increase. In addition, these patients present with low muscle tone, ligamental laxity, blue sclera, reduced physical growth, dental problems, and alterations in motor development. The aim of the present study is to know the effects of physiotherapy on fine and gross motor development in children with osteogenesis imperfecta. Methods Systematic review of clinical trials and observational studies on physiotherapeutic treatment in children with osteogenesis imperfecta. The computerized databases Medline, BASE, Cochrane, EBSCO, SCOPUS, and Web of Science were used in the literature search. Results One hundred and two articles were identified on the databases. After screening by inclusion criteria and removing duplicates, 4 articles were included in this study. In the 4 articles, bias risk was assessed according to the Cochrane Systematic Review Manual. Muscle strength, motor function, fatigue, gait, aerobic resistance, and bone density were improved with physiotherapy treatment. Results are difficult to compare due to the heterogeneity of the studies. Conclusions Physical therapy can improve gross motor skills in children with osteogenesis imperfecta. A larger number of studies with a better methodological quality are necessary to confirm the results with more evidence (AU)

Osteogenesis Imperfecta: Current and Prospective Therapies.

Osteogenesis Imperfecta (OI) is a group of connective tissue disorders with a broad range of phenotypes characterized primarily by bone fragility. The prevalence of OI ranges from about 1:15,000 to 1:20,000 births. Five types of the disease are commonly distinguished, ranging from a mild (type I) to a lethal one (type II). Types III and IV are severe forms allowing survival after the neonatal period, while type V is characterized by a mild to moderate phenotype with calcification of interosseous membranes. In most cases, there is a reduction in the production of normal type I collagen (col I) or the synthesis of abnormal collagen as a result of mutations in col I genes. Moreover, mutations in genes involved in col I synthesis and processing as well as in osteoblast differentiation have been reported. The currently available treatments try to prevent fractures, control symptoms and increase bone mass. Commonly used medications in OI treatment are bisphosphonates, Denosumab, synthetic parathyroid hormone and growth hormone for children therapy. The main disadvantages of these therapies are their relatively weak effectiveness, lack of effects in some patients or cytotoxic side effects. Experimental approaches, particularly those based on stem cell transplantation and genetic engineering, seem to be promising to improve the therapeutic effects of OI.

Knowledge, attitude and practices regarding health self-management among patients with osteogenesis imperfecta in China: an online cross-sectional survey.

OBJECTIVES: Assessing the knowledge, attitude and practices (KAP) regarding health self-management among patients with osteogenesis imperfecta (OI) in China. DESIGN: An online cross-sectional survey. SETTING: A structured questionnaire was distributed online through China-Dolls Center for Rare Disorders (CCRD), a non-governmental charity in China. PARTICIPANTS: Participants were all patients with OI from CCRD. After stratified sampling according to the economic level of residential city, 901 patients were proportionally selected and 869 patients completed the survey (response rate: 96.4%). MAIN OUTCOME MEASURES: Demographic characteristics and KAP information were gathered using a 5-point Likert scale. The score of each dimension of KAP was the sum of the scores of all included items. Χ2 test or Fisher's exact test was used to compare scores of different items. Ordinal regression was employed to determine the significant factors influencing KAP. RESULTS: A total of 802 questionnaires were included for analysis. Male respondents accounted for 57.1%, and 29.1% of respondents were of 26~30 years. More than half (50~60%) of patients knew the main symptoms of OI and the treatment of OI-related complications. Almost 80% of patients showed positive attitude. Nearly 60~70% of the patients were relatively able to take appropriate practice regarding OI management. There was a significant correlation between scores of knowledge and attitude, attitude and practice, as well as knowledge and practice. Patients aged 26~30 years, from urban areas and big cities, had higher KAP scores. Male patients showed better performance in knowledge, and highly educated patients perform better in practice. CONCLUSIONS: Patients with OI did not have sufficient knowledge on disease care and up-to-date caring guidelines, and their practice regarding health self-management also needs to be improved. Gender, age, educational level and economic level of residence can affect the level of KAP for patients, thus developing targeted and tailored programmes for patients with OI is highly recommended.

Mesenchymal Stem Cell Therapy for Osteogenesis Imperfecta.

The aim of this study was to provide a brief overview on the background and rationale on treating fetuses and children suffering from osteogenesis imperfecta (OI) with mesenchymal stem cells (MSCs). MSCs ability to migrate, engraft, and differentiate into bone cells and to act via paracrine effects on the recipient's tissues makes these cells promising candidates as a clinical therapy for OI. Animal work and limited clinical studies in humans support the use of MSC in treating OI. Off-the-shelf MSC have a good safety profile and exhibit multilineage differentiation potential and a low immunogenic profile and thereby may enable this potential therapy to become widely available. MSC transplantation before and after birth to treat OI is an experimental therapy that is currently tested in the international multicentre phase I/II clinical trial BOOSTB4 that aims to assess the safety and efficacy of fetal MSC transplantation for the treatment of severe types of OI.