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.

Osteogenesis Imperfecta: Skeletal and Non-skeletal Challenges in Adulthood.

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which involves not only the skeleton, but also the cardiopulmonary and gastrointestinal system, soft tissues, tendons, muscle, and joints, hearing, eyesight, dental health, and women's health in OI and potentially adds negative affect to health-related quality of life. We aim to guide clinicians as well as draw attention to obvious knowledge gaps and the need for further research in adult OI.

The IMPACT Survey: the economic impact of osteogenesis imperfecta in adults.

BACKGROUND: The IMPACT survey aimed to elucidate the humanistic, clinical and economic burden of osteogenesis imperfecta (OI) on individuals with OI, their families, caregivers and wider society. Research methodology, demographics and initial insights from the survey have been previously reported. The cost of illness (healthcare resource use, productivity loss, out-of-pocket spending) and drivers of the economic impact of OI are reported here. METHODS: IMPACT was an international mixed-methods online survey in eight languages (fielded July-September 2021) targeting adults (aged ≥ 18 years) or adolescents (aged ≥ 12-17 years) with OI, caregivers with or without OI and other close relatives. Survey domains included demographics, socioeconomic factors, clinical characteristics, treatment patterns, quality of life and health economics. The health economic domain for adults, which included questions on healthcare resource use, productivity loss and out-of-pocket spending, was summarised. Regression and pairwise analyses were conducted to identify independent drivers and associations with respondent characteristics. RESULTS: Overall, 1,440 adults with OI responded to the survey. Respondents were mostly female (70%) and from Europe (63%) with a median age of 43 years. Within a 12-month period, adults with OI reported visiting a wide range of healthcare professionals. Two-thirds (66%) of adults visited a hospital, and one-third (33%) visited the emergency department. The mean total number of diagnostic tests undergone by adults within these 12 months was 8.0. Adults had undergone a mean total of 11.8 surgeries up to the time point of the survey. The proportions of adults using queried consumables or services over 12 months ranged from 18-82%, depending on the type of consumable or service. Most adults (58%) were in paid employment, of which nearly one-third (29%) reported missing a workday. Of the queried expenses, the mean total out-of-pocket spending in 4 weeks was €191. Respondent characteristics such as female sex, more severe self-reported OI and the experience of fractures were often associated with increased economic burden. CONCLUSION: IMPACT provides novel insights into the substantial cost of illness associated with OI on individuals, healthcare systems and society at large. Future analyses will provide insights into country-specific economic impact, humanistic impact and the healthcare journey of individuals with OI.

The IMPACT survey: a mixed methods study to understand the experience of children, adolescents and adults with osteogenesis imperfecta and their caregivers.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare, heritable connective tissue disorder associated with a variety of symptoms, that affect individuals' quality of life (QoL) and can be associated with increased healthcare resource use. While some aspects of OI are well studied, others remain poorly understood. Therefore, the IMPACT survey aimed to elucidate the humanistic, clinical and economic burden of OI on individuals with OI, their families, caregivers and wider society. METHODS: We developed an international mixed methods online survey in eight languages (fielded July-September 2021), aimed at adults (aged ≥ 18 years) or adolescents (aged ≥ 12-17 years) with OI, caregivers (with or without OI) of individuals with OI and other close relatives. All respondents provided data on themselves; caregivers additionally provided data on individuals in their care by proxy. Data were cleaned, coded, and analysed using the pandas Python software package and Excel. RESULTS: IMPACT collected 2208 eligible questionnaires (covering 2988 individuals of whom 2312 had OI) including 1290 non-caregiver adults with OI, 92 adolescents with OI, 150 caregiver adults with OI, 560 caregivers for individuals with OI, 116 close relatives and 780 proxy care-recipients with OI. Most individuals with OI (direct or proxy) described their OI as moderate (41-52% across populations) and reported OI type 1 (33-38%). Pain (72-82%) was the most reported clinical condition experienced in the past 12 months and was also most frequently rated as severely or moderately impactful. Further, among adults, 67% reported fatigue, 47% scoliosis, and 46% sleep disturbance; in adolescents, fatigue affected 65%, scoliosis and other bone problems 60%, and mental health problems 46%; in children, fractures were common in 67%, fatigue in 47%, and dental problems in 46%. CONCLUSION: IMPACT has generated an extensive dataset on the experience of individuals with OI, their caregivers and relatives. We found that, irrespective of age, individuals with OI experience numerous and evolving symptoms that affect their QoL; however, pain and fatigue are consistently present. Upcoming analyses will provide further insights into the economic impact, healthcare journey and caregiver wellbeing, aiming to contribute to improved treatment and care for the OI community.

ERN BOND: The key European network leveraging diagnosis, research, and treatment for rare bone conditions.

There is no universally accepted definition for rare diseases: in Europe a disease is considered to be rare when affecting fewer than 1 in 2000 people. European Reference Networks (ERNs) have been the concrete response to address the unmet needs of rare disease patients and many pan-European issues in the field, reducing inequities, and significantly increasing accessibility to high-quality healthcare across Europe. ERNs are virtual networks, involving centres and patient representatives with the general scope to facilitate discussion on complex cases requiring highly specialised competences and trained expertise. ERN BOND - the European Reference Network on rare BONe Diseases - is one of these 24 approved networks with the specific ongoing mission to implement measures facilitating multidisciplinary, holistic, continuous, patient-centred, and participative care provision to patients, and supporting them in the full realisation of their fundamental human rights. ERN BOND includes in 2023 a total of 53 centres of expertise from 20 European countries. Its governing structure installed in March 2017 includes decision-making, operative and consultative committees, which comprise experts in the field and patient representatives ensuring patient's voice and perspectives are taken into account. Over the years, ERN BOND has worked hard to achieve its mission and valuably contribute to the advancement of diagnosis, management, treatment, and research in rare diseases. The network activities are mainly related to (i) the provision of care which collectively involves averagely 2800 patients diagnosed per year, (ii) the development of education for and training of the healthcare personnel consisting until now in the realisation of 7 thematic workshops and 19 webinars, (iii) the dissemination and exchange and spread of knowledge via network's website (https://ernbond.eu/), social media channels, and newsletters, (iv) the management of related data through a disease registry currently mapping over 2300 cases and recording over 600 reported cases, and (v) the enhancement of research which now include two clinical trials endorsed by the network. ERN BOND represents therefore an unprecedented move to improve the healthcare management of patients suffering from rare bone diseases through European collaborations. This network, through the support from the European Health Programme, will continue to pursue its efforts to achieve its goals, always maintaining the patients and their families at the centre of healthcare services.

The range of publications on arthrogryposis multiplex congenita from 1995 to 2022-A scoping review.

Arthrogryposis multiplex congenita (AMC) is defined as "a group of congenital conditions characterized by joint contractures in two or more body areas." Given its heterogeneity, the definition of AMC has changed multiple times. This scoping review provides an overview of how AMC is defined in scientific publications, on existing knowledge and trends regarding the concept of AMC. Our review illuminates possible knowledge gaps and provides directions for future research. A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Quantitative studies on AMC from 1995 to date were included. We summarized information about definitions/descriptions of AMC, study objectives, study designs, methods, funding, and involvement of patient organizations. A total of 2729 references were screened, and 141 articles fulfilled our inclusion criteria. Our scoping revealed that the majority of publications were cross-sectional or retrospective studies of children and young people, commonly about orthopedic management. Explicit or good definitions of AMC were provided in 86% of the cases. Recent publications on AMC mostly used consensus-based definitions. The research gaps were primarily related to adults, aging, etiology, and new medical treatment, in addition to implications on daily life.

The patient clinical journey and socioeconomic impact of osteogenesis imperfecta: a systematic scoping review.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare heritable connective tissue disorder primarily characterised by skeletal deformity and fragility, and an array of secondary features. The purpose of this review was to capture and quantify the published evidence relating specifically to the clinical, humanistic, and economic impact of OI on individuals, their families, and wider society. METHODS: A systematic scoping review of 11 databases (MEDLINE, MEDLINE in-progress, EMBASE, CENTRAL, PsycINFO, NHS EED, CEA Registry, PEDE, ScHARRHUd, Orphanet and Google Scholar), supplemented by hand searches of grey literature, was conducted to identify OI literature published 1st January 1995-18th December 2021. Searches were restricted to English language but without geographical limitations. The quality of included records was assessed using the AGREE II checklist and an adapted version of the JBI cross-sectional study checklist. RESULTS: Of the identified 7,850 records, 271 records of 245 unique studies met the inclusion criteria; overall, 168 included records examined clinical aspects of OI, 67 provided humanistic data, 6 reported on the economic impact of OI, and 30 provided data on mixed outcomes. Bone conditions, anthropometric measurements, oral conditions, diagnostic techniques, use of pharmacotherapy, and physical functioning of adults and children with OI were well described. However, few records included current care practice, diagnosis and monitoring, interactions with the healthcare system, or transition of care across life stages. Limited data on wider health concerns beyond bone health, how these concerns may impact health-related quality of life, in particular that of adult men and other family members, were identified. Few records described fatigue in children or adults. Markedly few records provided data on the socioeconomic impact of OI on patients and their caregivers, and associated costs to healthcare systems, and wider society. Most included records had qualitative limitations. CONCLUSION: Despite the rarity of OI, the volume of recently published literature highlights the breadth of interest in the OI field from the research community. However, significant data gaps describing the experience of OI for individuals, their families, and wider society warrant further research to capture and quantify the full impact of OI.

Physical functioning and activities of daily living in adults with amyoplasia, the most common form of arthrogryposis. A cross-sectional study.

BACKGROUND: Amyoplasia, the most common form of arthrogryposis is characterized by typical deformities of the joints and replacement of skeletal muscles by fibrous tissue and fat. There is sparse literature on adaptation to adult life with amyoplasia. PURPOSE: To describe physical function and activity strategies in adults with amyoplasia, as this knowledge is important for relevant function-enhancing measures. MATERIALS AND METHODS: Twenty-two adults (20-91 years) with amyoplasia participated. Demographic factors and clinical history were registered. Body proportions were measured. Joint mobility and muscle strength in the upper limbs were examined. The Functional Independent Measure was used to assess performance of activities of daily living. Compensatory strategies were described. RESULTS: The majority had undergone comprehensive conservative and surgical treatment. Mean height was below typical. Range of motion was below lower limit of normal in most joints, passive range of motion was mainly larger than active. Muscle strength was reduced for most movements. Seven were independent in all activities. Need of assistance was highest regarding bathing and dressing. A variety of compensatory strategies were used. CONCLUSIONS: Adults with amyoplasia are heterogeneous regarding function. Independence in everyday life requires a combination of muscle strength to move against gravity, ability to passive joint motion, and use of compensatory strategies. Implications for rehabilitation The ability to joint motion in the upper extremities is essential for independency in activities of daily living, especially when the muscle strength is impaired. Training of muscle strength is recommended, whenever possible, as muscle strength to move against gravity makes the performing of everyday tasks easier. The use of compensatory techniques, adaptions to the environment and relevant, often custom made, assistive devices is required to perform activities of daily living. Living an active life with physical challenges like in amyoplasia requires flexible and individually adapted solutions.

Bone mass, bone markers and prevalence of fractures in adults with osteogenesis imperfecta.

UNLABELLED: Still little is known about the manifestations of osteogenesis imperfecta (OI) in adults. We therefore initiated this study of bone mass, bone turnover and prevalence of fractures in a large cohort of adult patients. We found a surprising low prevalence (10%) of osteoporosis. These patients, however, expressed the most severe disease. PURPOSE: To characterize bone mineral density, bone turnover, calcium metabolism and prevalence of fractures in a large cohort of adults with osteogenesis imperfecta. METHODS: One hundred fifty-four patients with adult OI participated and 90 (age range 25-83) provided dual X-ray absorptiometry (DXA) measurements. According to Sillence classification criteria, 68 persons were classified as OI type I, 9 as type III, 11 type IV and 2 were unclassified. Fracture numbers were based on self-reporting. Biochemical markers of bone turnover were measured and bone mineral density (BMD) of the spine, femoral neck and total body were determined by DXA. RESULTS: Only 10% of adults with OI exhibited osteoporotic T scores (T ≤ -2.5) but compared to patients with normal T scores this subgroup had a threefold higher fracture risk (22 vs. 69). s-PTH, s-Ca and 25[OH] vitamin D were all normal. Bone markers did not display major deviations from normal, but patients with OI type III displayed higher resorption marker levels than type I and IV. Multivariate regression analysis showed that only gender and total body BMD were significant determinants of fracture susceptibility, and the differences for total body BMC, BMD and Z scores were significant between the OI subtypes. CONCLUSIONS: In adult OI, DXA measurements only identified few patients as osteoporotic. These patients, however, exhibited a much higher fracture propensity. Due to deformities, low body height and pre-existing fractures, DXA assessment is complicated in this disease, and further studies are needed to work out how to minimize the impact of these confounders.

A population-based study of demographical variables and ability to perform activities of daily living in adults with osteogenesis imperfecta.

PURPOSES: To describe demographical variables, and to study functional ability to perform activities of daily life in adults with osteogenesis imperfecta (OI). METHODS: Population-based study. Ninety-seven patients aged 25 years and older, 41 men and 56 women, were included. For the demographical variables, comparison was made to a matched control-group (475 persons) from the Norwegian general population. Structured interviews concerning social conditions, employment and educational issues and clinical examination were performed. The Sunnaas Activities of Daily Living (ADL) Index was used to assess the ability to perform ADL. RESULTS: The prevalence of clinical manifestations according to Sillence was in accordance with other studies. Demographical variables showed that most adults with OI are married and have children. They had a higher educational level than the control group, but the employment rate was significantly lower. However, the rate of employed men was similar in both groups. Adult persons with OI achieved a high score when tested for ADL. CONCLUSIONS: Adults with OI are well educated compared with the general population, and most of them are employed. High scores when tested for ADL indicate that most of them are able to live their lives independently, even though there are some differences according to the severity of the disorder.

[Ehlers-Danlos syndrome--diagnosis and subclassification]. / Ehlers-Danlos' syndrom--diagnostikk og subklassifisering.

BACKGROUND: Ehlers-Danlos syndrome is the most frequent heritable connective tissue disorder, and a differential diagnosis to known disorders of the muscle and skeletal system. Defects in collagen fibres may lead to hyperelasticity and fragility of connective tissue, which again may result in joint problems, hernia, and rupture of blood vessels and inner organs. MATERIAL AND METHOD: This review and discussion is based on articles identified by a PubMed search and personal clinical experience at rehabilitation and counselling departments. RESULTS AND INTERPRETATION: Ehlers-Danlos syndrome has through the years been classified into different subtypes. Diagnostics is primarily a clinical task. The present diagnostic criteria for the syndrome and its subtypes are listed in the Villefranche nosology. According to this nosology, the hypermobility type is identical with the familial joint hypermobility syndrome. In the classical type, manifestations of the skin are important. The vascular type may result in fatal bleedings. Precise diagnostic criteria are important for differential diagnostics, rehabilitation, medical follow-up, and genetic counselling. We encourage use of the Villefranche classification and the associated criteria, although some of the manifestations could have been more accurately defined. Thorough examinations and accurate clinical descriptions of patients may enable studies of correlations between genotype and phenotype that could form the basis for use of molecular genetic diagnostics.