Oral Problems in Brazilian Individuals with Rare Genetic Diseases That Affect Skeletal Development.

The present study aimed to compare the prevalence of oral problems between individuals with rare genetic diseases that affect skeletal development and individuals without rare diseases. A cross-sectional study was conducted with 210 individuals between two and fifty-four years of age: 105 with rare genetic diseases (27 with mucopolysaccharidosis [MPS] and 78 with osteogenesis imperfecta [OI]) and 105 without rare diseases. The rare genetic disease group was recruited from hospital units that provide care for patients with MPS and OI in five states of Brazil, and the other group was recruited from the same location. The participants were examined with regards to malocclusion, dental anomalies, dental caries, and gingivitis. A questionnaire was administered addressing individual, sociodemographic, and behavioral characteristics as well as dental history. A descriptive analysis was performed, followed by unadjusted and adjusted binary logistic regression analyses. The mean age was 14.1 ± 12.2 years. Individuals with a rare disease were 12.9-fold more likely to have some type of oral problem (95% CI: 3.7-44.7) compared to the group without rare diseases. The prevalence of oral problems was higher among Brazilians with MPS and OI compared to normotypical individuals.

The PATCH study: Prevalence of Hearing Loss During Ageing and Treatment Choices in Osteogenesis Imperfecta: A Danish Nationwide Register-Based Cohort Study.

Osteogenesis imperfecta (OI) is a group of rare hereditary collagen disorders. Hearing loss (HL) is a known complication linked to changes in the bones of the middle ear seen in OI. We aimed to determine the prevalence, age at debut, incidence, and risk of HL, surgery on bones of the middle ear, and use of hearing aids. A Danish nationwide, register-based cohort study. Data were extracted from the Danish National Patient register. Anyone with an OI diagnosis between January 1st 1977 and December 31st 2018, matched 1:5 with a reference population (Ref.Pop) on birthyear and sex, were included. 864 persons (487 women) with OI were included in the study and 4276 (2330 women) in the Ref.Pop. The sub-hazard ratio (SHR) for any HL was 4.56 [95% CI 3.64-5.71], with a prevalence of 17.0% and 4.0% in the OI cohort and Ref.Pop. Median age at debut was 42 and 58 years, respectively. The risk of otosclerosis and/or surgery was higher in the OI cohort (SHR 22.51 [95% CI 12.62-40.14]), with a median age at debut of 43 and 32 years in the OI cohort and Ref.Pop, respectively. Hearing aid use was more frequent in the OI cohort (SHR 4.16 [95% CI 3.21-5.40]) than in the Ref.Pop. The median age at debut was 45 and 60 years in the OI cohort and Ref.Pop, respectively. Persons with OI have a higher risk and prevalence of HL, hearing aids, and surgery, debuting younger, and prevalence increases with age.

Pregnancy complications and birth outcome in patients with osteogenesis imperfecta - A population-based register study.

OBJECTIVE: Patients with Osteogenesis Imperfecta (OI) have varying degrees of bone fragility and increased fracture rates. There is a paucity of data related to complications to pregnancies in patients with OI and to their offspring. With this study we aim to evaluate the risk of complications to pregnancies, delivery, and offspring in pregnancies where the mother or father have OI. DESIGN: Nationwide, register-based, cohort study. SETTING: Danish health register-based data. POPULATION: All pregnancies registered in the Danish health registers where one parent has OI and a reference population of all other pregnancies in the general population from 1997 to 2018. METHODS: Descriptive epidemiology MAIN OUTCOME MEASURES: Pregnancy and delivery complications (e.g. prevalence of pre-eclampsia, eclampsia and perinatal haemorrhage), and complications in the offspring (e.g. prevalence of low birth weight, low Apgar Score, need of CPAP or NICU, prevalence of congenital malformations (using the EUROCAT classification), incidence of osteogenesis imperfecta, prevalence of birth related fractures and hospital contacts during the first year of life) from pregnancies with parental OI. RESULTS: We identified 433 OI related pregnancies among 134 mothers with OI and 73 fathers with OI. The rates of pregnancy and delivery complications were similar between the OI cohorts and the reference population. More (31 % vs 19 %) children were delivered by caesarean section in the OI cohort than in the reference population. CONCLUSION: Pregnancies, where one parent have OI, result in live births to term with very few complications.

Evaluation of the Nordic Musculoskeletal Questionnaire for Measuring Prevalence and the Consequence of Pain in a Danish Adult OI Population: A Pilot Study.

Pain is a challenge in persons with OI and causes much concern in the Osteogenesis Imperfecta (OI) population. We aim to evaluate the usability of the Nordic Musculoskeletal Questionnaire (NMQ) to identify painful sites in adults with OI and to describe the occurrence of musculoskeletal (MSK) pain and its impact on their work and daily activities. This cross-sectional pilot study uses the OI-NMQ to study MSK pain prevalence in nine separate anatomical regions (neck, upper back, lower back, shoulder, elbow, hand/wrist, hip, knee, and ankle/foot) and its impact on regular work and daily activities in adults with OI. The questionnaire was distributed among participants of the 2023 annual meeting of The Danish OI Society. The response rate was 68%, and all participants considered the OI-NMQ helpful in assessing the presence of pain and its consequences. The analysis included 27 adults with OI type I, III, or IV above 18 years. Among all 27 participants, MSK pain was present in 15-56% of the 9 sites within the last 7 days and 33-89% of the nine anatomical regions during the last 12 months. In 7-48% of all the participants, their regular work and daily activities had been affected by the presence of MSK pain. The OI-NMQ was feasible in assessing MSK pain among adults with OI and displayed a high prevalence of MSK pain with a moderate impact on their regular work and daily activities in this OI population. A larger and repeated measurement of MSK pain in adults with OI is needed to confirm these results.

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

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.

Demographics and medical burden of osteogenesis imperfecta: a nationwide database analysis.

The epidemiological data on osteogenesis imperfecta (OI) in Asia is limited. This study, representing the first comprehensive epidemiological investigation on OI in Taiwan, reveals high medical resource utilization and underscores the importance of early diagnosis to enhance care quality. INTRODUCTION: This study examines osteogenesis imperfecta, a hereditary connective tissue disorder causing pediatric fractures and limb deformities, using a nationwide database from Taiwan to analyze clinical features and medical burden. METHODS: The study identified validated OI patients from the Catastrophic Illness Registry in the National Health Insurance Research Database from 2008 to 2019. Demographic data and medical resource utilization were analyzed. A multivariate Cox model assessed the influence of sex, validation age, and comorbidities. RESULTS: 319 OI patients (M/F = 153/166) were identified, with 58% validated before age 20. Prevalence and incidence were 0.8-1.3/100,000 and 0.02-0.09/100,000, respectively, with higher rates in the pediatric demographic. In the study period, 69.6% of the patients had admission history, primarily to pediatric and orthopedic wards. The median admission number was 3, with a median length of stay of 12 days and a median inpatient cost of approximately 3,163 USD during the period. Lower limb fractures were the main reason for hospitalization. 57% of OI patients received bisphosphonate treatment. The leading causes of mortality were OI-related deaths, neurovascular disease, and cardiovascular disease. The median age of validation in the non-survival group was significantly higher compared to the survival group (33 vs. 14 years), and patients validated during childhood required more inpatient fracture surgeries than those validated during adulthood. CONCLUSION: This study provides comprehensive real-world evidence on the clinical characteristics and high medical resource utilization of OI patients in a low prevalence region like Taiwan. Early diagnosis is crucial for improving care quality and enhancing health outcomes.

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.

The burden of hospital admissions for skeletal dysplasias in Sri Lanka: a population-based study.

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.

Dental anomalies in individuals with osteogenesis imperfecta: a systematic review and meta-analysis of prevalence and comparative studies.

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).

The patient-related factors in revision procedures on tibia of patients with osteogenesis imperfecta treated with the Peter-Williams nail.

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.

Pediatric Hand and Wrist Fractures in Osteogenesis Imperfecta: An Analysis of Incidence, Patient-specific Risk Factors, and Fracture-specific Characteristics.

BACKGROUND: Children with osteogenesis imperfecta (OI) frequently present with fractures; however, hand and wrist fractures (HWFs), those distal to the radial and ulnar diaphysis, are seldom observed. Yet, HWFs remain among the most common fractures in children with non-OI. The objective of this study was to identify the incidence of OI HWFs. Secondary objectives aimed at identifying patient-specific risk factors for HWFs in OI and comparing clinical courses to non-OI HWFs. METHODS: A retrospective cohort study was conducted. Database query by ICD-10 codes identified 18 patients with OI HWF, 451 patients with OI without HWFs, and 26,183 patients with non-OI HWF. Power analysis estimated appropriate sample sizes and random sampling was utilized to collect patients. Patient demographics, OI-specific variables, fracture morphology, and fracture clinical courses were recorded. Data were analyzed for patient-specific and fracture-specific factors affecting OI HWF incidence. RESULTS: Of patients with OI, 3.8% (18/469) sustained HWFs. Patients with OI HWF were significantly older than patients with OI without HWFs ( P = 0.002) with no differences in height, weight, ethnicity, sex, or ambulatory status. Compared with non-OI HWFs, patients with OI HWF were significantly shorter ( P < 0.001), weighed less ( P = 0.002), and were less likely to be ambulatory ( P < 0.001). OI HWFs were more commonly on the side of hand dominance ( P < 0.001) with transverse patterns ( P = 0.001). OI HWFs were less frequent in the thumb ( P = 0.048) and trended towards significance in the metacarpals ( P = 0.054). All OI HWFs were treated nonoperatively with similar union rates and refracture rates to non-OI HWFs. Multivariate regression showed that older patient age (odds ratio: 1.079, 95% CI: 1.005,1.159, P = 0.037) and OI type I (odds ratio: 5.535, 95% CI: 1.069, 26.795, P = 0.041) were significant prognosticators for HWFs in patients with OI. CONCLUSION: OI HWFs are uncommon (3.8%, 18/469) but specific HWF morphologies and locations are more common in patients with OI; however, these are not pathognomonic. Older patients with mild penetrance of type I OI are at the highest risk for HWFs. OI HWFs do well when managed nonoperatively with noninferior clinical courses compared with non-OI HWFs. LEVEL OF EVIDENCE: Level III.

Tibial plateau fracture and RNA sequencing with osteogenesis imperfecta: a case report.

Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis. Case presentation: A 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)-receptor interactions. Conclusion: In this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.

Systematic review of health related-quality of life in adults with osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare, connective tissue disorder characterised by bone fragility, resulting in recurrent fractures and skeletal deformities. Extra-skeletal manifestations include dentinogenesis imperfecta, hearing abnormalities and lung disease. These co-morbidities combined with recurrent fractures can exert a significant impact on health-related quality of life (HR-QOL). It is important to assess HR-QOL throughout adulthood because the prevalence of some OI-specific complications increases with age. METHODS: PubMed, EMBASE and CENTRAL databases were searched on 2nd February 2022 to identify studies reporting quantitative assessments of HR-QOL in adults with OI. The primary endpoint was to determine the impact of an OI diagnosis on adult's HR-QOL. Secondary endpoints were to (i) examine how frequently various HR-QOL assessment tools were used (ii) identify differences in HR-QOL between OI types and (iii) investigate the determinants of HR-QOL in adults with OI. Search results were exported to Endnote where two reviewers independently conducted title/abstract and full-text reviews. Data from accepted studies were extracted into Microsoft Excel. A narrative synthesis was then undertaken. RESULTS: The review identified 17 studies with a total of 1,648 adults. The Short Form-36 (SF-36) was the most frequently reported HR-QOL assessment tool and was used in nine studies. Physical HR-QOL was reduced in adults with OI. Physical component scores (PCS) or individual physical domains of the SF-36 were lower in eight of nine studies. Mental component scores (MCS) were preserved in all six studies, however individual mental health domains of the SF-36 were reduced in some studies. The prevalence of anxiety/depression was relatively low in adults with OI. Those with type III OI had lower physical and respiratory HR-QOL but preserved mental HR-QOL compared with type I. The prevalence of fatigue and pain was higher in adults with OI compared with reference populations. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL. CONCLUSION: OI in adulthood has a wide-ranging negative impact on HR-QOL. Physical and respiratory HR-QOL were lower, while the prevalence of pain and fatigue were higher than in reference populations. Mental HR-QOL was relatively preserved, although some deficits were identified. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.

A multicenter study to evaluate pain characteristics in osteogenesis imperfecta.

The objective was to describe pain characteristics and treatments used in individuals with varying severity of osteogenesis imperfecta (OI) and investigate pain-associated variables. This work was derived from a multicenter, longitudinal, observational, natural history study of OI conducted at 12 clinical sites of the NIH Rare Diseases Clinical Research Network's Brittle Bone Disorders Consortium. Children and adults with a clinical, biochemical, or molecular diagnosis of OI were enrolled in the study. We did a cross-sectional analysis of chronic pain prevalence, characteristics, and treatments used for pain relief and longitudinal analysis to find the predictors of chronic pain. We included 861 individuals with OI, in 41.8% chronic pain was present, with similar frequency across OI types. Back pain was the most frequent location. Nonsteroidal anti-inflammatory drugs followed by bisphosphonates were the most common treatment used. Participants with chronic pain missed more days from school or work/year and performed worse in all mobility metrics than participants without chronic pain. The variables more significantly associated with chronic pain were age, sex, positive history of rodding surgery, scoliosis, other medical problems, assistive devices, lower standardized height, and higher body mass index. The predictors of chronic pain for all OI types were age, use of a wheelchair, and the number of fractures/year. Chronic pain is prevalent in OI across all OI types, affects mobility, and interferes with participation. Multiple covariates were associated with chronic pain.

Data collection on rare bone and mineral conditions in Europe: The landscape of registries and databases.

BACKGROUND: knowledge on the natural history of rare diseases is necessary to improve outcomes. Disease registries may play a key role in covering these unmet needs in the rare bone and mineral community. OBJECTIVE: to map existing bone and mineral conditions registries in Europe and their characteristics. METHODS: online survey about the use of registries/databases and their characteristics. This survey was disseminated among members of the European Reference Network on Rare Bone Diseases (ERN BOND) and non-ERN experts in the field of bone and mineral conditions as well as patient organisations. RESULTS: sixty-three responses from health care providers (HCPs) and 10 responses from patient groups (PGs) were collected. The response rate for ERN BOND members was 55%. Of 63 HCPs, 37 declared using a registry. Osteogenesis imperfecta (OI) was the most registered condition. We mapped 3 international registries, all were disease-specific. CONCLUSIONS: There is a need for developing a common high-quality platform for registering rare bone and mineral conditions.

Incidence and nonunion rates of tibial fractures in adults with osteogenesis imperfecta: a retrospective cohort study of 402 patients with 42 fractures at an expert clinic.

BACKGROUND: Tibial fractures are the most common fractures seen in adults and lead to the most nonunions. Osteogenesis imperfecta (OI) is characterized by increased bone fragility and higher risk of fractures. No studies have been published on the incidence of tibial fractures and nonunions in adults with OI. This study aims to summarize the incidence of tibial fractures and nonunions in this population. METHODS: A retrospective, descriptive study. All medical charts of adult patients in the OI database of our OI expert clinic were analyzed for tibial fractures between 2008 and 2020. Tibial fracture incidence, nonunion rate, treatment modality and potential risk factors were determined. RESULTS: The database consisted of 402 patients, 34 of whom had suffered one or more tibial fractures, resulting in 42 fractures. The incidence of tibial fractures in adults with OI is 870 per 100,000 person-years. Two out of 42 fractures led to nonunion (5%). It was not possible to adjust for risk factors or type of treatment. CONCLUSION: There is a higher incidence of tibial fractures in patients with OI, but a nonunion rate comparable to the general population. With only two nonunions it is not possible to draw conclusions on the influence of risk factors or treatment of tibial fractures on OI.

Anthropometrics of Polish children with osteogenesis imperfecta: a single-centre retrospective cohort study.

BACKGROUND: Osteogenesis imperfecta (OI) causes a number of abnormalities in somatic development. The predominant symptoms are reduced bone mass and an increased risk of fractures as well as bone deformities and short stature. Due to the lack of causal treatment options, bisphosphonates are considered the gold standard of therapy. The aim of our study is to present selected anthropometric parameters (body weight, height, BMI) in children with type I and III of OI. METHODS: We performed a retrospective analysis of medical records of patients with osteogenesis imperfecta type I and III confirmed by genetic testing. The study group included individuals admitted to the Department in 2020. We analysed the anthropometric parameters of 108 children (receiving and not receiving bisphosphonates treatment). RESULTS: In the group of children with OI type I admitted for follow-up (group 1), the median weight percentile was 37, while in the group 2 it was 17. In the patients with OI type III (group 3), the median weight percentile was 0.1. The median height percentile in group 1 was 21, in group 2 it was 5, whereas in group 3 = 0.1. The differences in anthropometric measurements of the patients with OI type I and OI type III were statistically significant (p < 0.001). Among the analysed patients, an abnormal BMI was found in 41.67% of whom 37.78% were underweight, 48.89% were overweight and 13.33% were obese. CONCLUSION: Considering prevalence of the disease, it is not only low stature but also abnormal BMI, and especially excessive body weight, that play an important role in the somatic development disorder.

Exploring pain interference and self-perceived health status in children with osteogenesis imperfecta - a cross-sectional study.

BACKGROUND: Chronic pain may affect and interfere in children's everyday life and can be present in children with Osteogenesis Imperfecta (OI). However, the knowledge is still sparse to what extent pain is present, how pain interfere in children's everyday life and affect their self-perceived health status. The purpose of the study was therefore to explore presence of chronic pain, pain interference in daily life, and self-perceived health status in children with OI. METHODS: Children with OI, aged 6-18 years, were recruited consecutively to this cross-sectional study. Participants answered a standardised interview including five pre-structured questions, and the Numeric Pain Rating Scale (NPRS), the Pain Interference Index, and a questionnaire concerning self-perceived health status the Patient Reported Outcomes Measurement Information System Pediatric-25 Profile v1.1 (PROMIS-25). RESULTS: Twenty-eight children (median: 11 years, IQR 6) with OI type I, III, or IV participated. Pain was present in 27 of 28 children and interfered in their everyday life regardless of OI-type, sex, and age. The median NPRS for average pain intensity was 4 (IQR 2), the median for pain frequency was 2-3 times/week, and the median frequency of school absence due to pain was 2-3 times per month. The most common pain locations were back and feet. Pain in the feet was more frequently reported in children with type I (p = 0.032), and pain in the hip was more often reported in children ≥13 years (p = 0.011). The children were asked what they thought to be the cause of pain and the most frequent response was "walking long distances". Self-perceived health status for mobility was lower than the general population, and lowest for children with type III (p = 0.016). Pain interference was associated with children's self-perceived health status (rs = 0.84, p < 0.001). CONCLUSION: Almost all children experienced pain, which interfered in children's everyday lives, affected participation in various activities and was associated with reduced self-perceived health status. If children avoid physical activities because of pain, it might cause a vicious circle of inactivity, which further decreases bone density and increase the risk of fractures. The results emphasize the importance to offer adequate pain reducing interventions.

Prevalence and Hospital Admissions in Patients With Osteogenesis Imperfecta in The Netherlands: A Nationwide Registry Study.

Osteogenesis Imperfecta (OI) is a complex disease caused by genetic alterations in production of collagen type I, and collagen-related proteins. Bone fragility is the most common patient issue, but extraskeletal complications also present an adverse factor in the quality of life and prognosis of patients with OI. However, still little is known about the morbidity and mortality of these patients. The objective of this paper is to determine and describe to what extent OI impacts patients' life in terms of hospitalization and complications describing the incidence and prevalence of the Dutch cohort of OI patients and the characteristics of their hospital admissions. Information regarding OI patients and their hospital admission was extracted from the Statistics Netherlands Database and matched to the OI Genetics Database of Amsterdam UMC. Hospital admission data was available for 674 OI patients. This OI nationwide registry study shows that the life expectancy of OI patients is adversely affected by the disease. The median annual incidence risk of OI between 1992 and 2019 was 6.5 per 100,000 live births. Furthermore, patients with OI had a 2.9 times higher hospitalization rate compared to the general Dutch population. The highest hospitalization rate ratio of 8.4 was reported in the patient group between 0 and 19 years old. OI type and severity had impact on extraskeletal manifestations, which play a key role in the numerous hospital admissions. More awareness about the impact of OI on patients' life is needed to improve and implement prevention and follow-up guidelines.

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.