10-m shuttle ride test in youth with osteogenesis imperfecta who use wheelchairs : Feasibility, reproducibility, and physiological responses

Background: Physical fitness levels in youth with osteogenesis imperfecta (OI) who use wheelchairs are unknown. The 10-m Shuttle Ride Test (SRiT) has recently been introduced as a field test to determine cardiorespiratory fitness in children with cerebral palsy who selfpropel a wheelchair. Objective: The purpose of this study was to investigate the feasibility and reproducibility of the SRiT, as well as the physiological responses to the SRiT, in youth with moderate-to-severe OI between 8 and 25 years of age who self-propel a wheelchair at least for long distances. Design: A test-retest design was used. Methods: Thirteen patients with OI (8 boys, 5 girls; mean±SD values for age=15.5±6.4 years) using a manual wheelchair performed 2 SRiTs within 2 weeks. Adverse events, reached stage, peak heart rate (HRpeak), peak respiratory exchange ratio (RERpeak), peak oxygen uptake (VO2peak), and peak minute ventilation (VEpeak) were the main outcome parameters. Results and Discussion. All participants performed a maximal effort at both SRiTs (mean±SD values for HRpeak of 195±9 beats per minute [bpm], RERpeak of 1.32±0.16, VO2peak of 25.4±5.6 mL·kg−1·min−1, and VEpeak of 47.9±18.6 L·min−1), without adverse events. The intraclass correlation coefficient of the reached stage showed excellent reliability (.95). Limits of agreement (LoA) analysis revealed acceptable LoA for reached stage (mean bias=−0.58, range=−2.50 to −1.35). There was a low correlation between reached stage and VO2peak (r=.61 and r=.45 for the first and second SRiTs, respectively). Limitations: The influence of wheelchair properties and individually adjusted wheelchair designs was not examined. Conclusions: The SRiT appears to be a feasible, safe, and reproducible maximal field test in youth with OI using wheelchairs at least for long distances. This field test might be useful to provide an indication of physical fitness and to assess the efficacy of interventions on physical fitness in these patients

10-m shuttle ride test in youth with osteogenesis imperfecta who use wheelchairs : Feasibility, reproducibility, and physiological responses

Background: Physical fitness levels in youth with osteogenesis imperfecta (OI) who use wheelchairs are unknown. The 10-m Shuttle Ride Test (SRiT) has recently been introduced as a field test to determine cardiorespiratory fitness in children with cerebral palsy who selfpropel a wheelchair. Objective: The purpose of this study was to investigate the feasibility and reproducibility of the SRiT, as well as the physiological responses to the SRiT, in youth with moderate-to-severe OI between 8 and 25 years of age who self-propel a wheelchair at least for long distances. Design: A test-retest design was used. Methods: Thirteen patients with OI (8 boys, 5 girls; mean±SD values for age=15.5±6.4 years) using a manual wheelchair performed 2 SRiTs within 2 weeks. Adverse events, reached stage, peak heart rate (HRpeak), peak respiratory exchange ratio (RERpeak), peak oxygen uptake (VO2peak), and peak minute ventilation (VEpeak) were the main outcome parameters. Results and Discussion. All participants performed a maximal effort at both SRiTs (mean±SD values for HRpeak of 195±9 beats per minute [bpm], RERpeak of 1.32±0.16, VO2peak of 25.4±5.6 mL·kg−1·min−1, and VEpeak of 47.9±18.6 L·min−1), without adverse events. The intraclass correlation coefficient of the reached stage showed excellent reliability (.95). Limits of agreement (LoA) analysis revealed acceptable LoA for reached stage (mean bias=−0.58, range=−2.50 to −1.35). There was a low correlation between reached stage and VO2peak (r=.61 and r=.45 for the first and second SRiTs, respectively). Limitations: The influence of wheelchair properties and individually adjusted wheelchair designs was not examined. Conclusions: The SRiT appears to be a feasible, safe, and reproducible maximal field test in youth with OI using wheelchairs at least for long distances. This field test might be useful to provide an indication of physical fitness and to assess the efficacy of interventions on physical fitness in these patients

Adults with osteogenesis imperfecta : Clinical characteristics of 151 patients with a focus on bisphosphonate use and bone density measurements

An expert center for adults with Osteogenesis Imperfecta (OI) has been founded at the Isala Hospital in Zwolle, the Netherlands to achieve optimal care for adults with OI. Clinical data such as patient history, Dual Energy X-ray Absorptiometry measurements and laboratory findings are collected with patient consent. This study provides an overview of clinical characteristics of the patients who visited the clinic during its first 5 years, a total of 151 patients. In this study, we focus on bisphosphonate use and bone density measurements at time of presentation at the expert center. As such, insight into the natural history of OI in adults will be increased. Analysing the data of a large group of adults with this rare disorder within a national expert center will allow detailed exploration of the course of OI over time

Adults with osteogenesis imperfecta: Clinical characteristics of 151 patients with a focus on bisphosphonate use and bone density measurements

An expert center for adults with Osteogenesis Imperfecta (OI) has been founded at the Isala Hospital in Zwolle, the Netherlands to achieve optimal care for adults with OI. Clinical data such as patient history, Dual Energy X-ray Absorptiometry measurements and laboratory findings are collected with patient consent. This study provides an overview of clinical characteristics of the patients who visited the clinic during its first 5 years, a total of 151 patients. In this study, we focus on bisphosphonate use and bone density measurements at time of presentation at the expert center. As such, insight into the natural history of OI in adults will be increased. Analysing the data of a large group of adults with this rare disorder within a national expert center will allow detailed exploration of the course of OI over time. Keywords: Osteogenesis imperfecta, Adult, Expert center, Fractures, Bisphosphonates, Bone densit

PLS3 Mutations in X-Linked Osteoporosis with Fractures

<p>Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F-actin) bundles, appears to be important in human bone health, on the basis of pathogenic variants in PLS3 in five families with X-linked osteoporosis and osteoporotic fractures that we report here. The bone-regulatory properties of PLS3 were supported by in vivo analyses in zebrafish. Furthermore, in an additional five families (described in less detail) referred for diagnosis or ruling out of osteogenesis imperfecta type I, a rare variant (rs140121121) in PLS3 was found. This variant was also associated with a risk of fracture among elderly heterozygous women that was two times as high as that among noncarriers, which indicates that genetic variation in PLS3 is a novel etiologic factor involved in common, multi-factorial osteoporosis.</p>

Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2

Osteogenesis imperfecta (OI) is characterized primarily by susceptibility to fractures with or without bone deformation. OI is genetically heterogeneous: over 20 genetic causes are recognized. We identified bi-allelic pathogenic KDELR2 variants as a cause of OI in four families. KDELR2 encodes KDEL endoplasmic reticulum protein retention receptor 2, which recycles ER-resident proteins with a KDEL-like peptide from the cis-Golgi to the ER through COPI retrograde transport. Analysis of patient primary fibroblasts showed intracellular decrease of HSP47 and FKBP65 along with reduced procollagen type I in culture media. Electron microscopy identified an abnormal quality of secreted collagen fibrils with increased amount of HSP47 bound to monomeric and multimeric collagen molecules. Mapping the identified KDELR2 variants onto the crystal structure of G. gallus KDELR2 indicated that these lead to an inactive receptor resulting in impaired KDELR2-mediated Golgi-ER transport. Therefore, in KDELR2-deficient individuals, OI most likely occurs because of the inability of HSP47 to bind KDELR2 and dissociate from collagen type I. Instead, HSP47 remains bound to collagen molecules extracellularly, disrupting fiber formation. This highlights the importance of intracellular recycling of ER-resident molecular chaperones for collagen type I and bone metabolism and a crucial role of HSP47 in the KDELR2-associated pathogenic mechanism leading to OI