Osteogenesis Imperfecta

Marini, Joan C.

doi:10.1002/9781119266594.ch113

Cited by 4 publications

(5 citation statements)

References 52 publications

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“…The marked differences in physical function across the OI types likely result from the wide array of clinical manifestations (i.e. growth deficiency, degree of skeletal dysplasia and frequency of fractures) which vary significantly in both presence and severity according to the phenotype [1,2].…”

Section: Discussionmentioning

confidence: 99%

“…Although this finding is difficult to reconcile with the extreme debilitating sequelae induced by fractures including, fear of fractures, pain and deformities, it is possible to hypothesise that the number of fractures could play a lesser role in the development of physical alterations than that reported in children. This could be related to the lower incidence of fractures [1] during adulthood than childhood, which might result in a longer recovery time and consequently in a partial restoration of the physical function and alleviating of the psychological distress.…”

Section: Discussionmentioning

confidence: 99%

“…Osteogenesis imperfecta (OI) is a genetic skeletal disorder, characterised by qualitative and quantitative abnormalities of type I collagen [1]. In approximately 80% of individuals with OI, a mutation in one of the COL1A1 or COL1A2 genes is believed to be responsible for the disorder 1 .…”

Section: Introductionmentioning

confidence: 99%

“…The main clinical feature of OI is decreased bone mineral density and bone fragility, leading to a high incidence of fractures, particularly in childhood [1]. The chronic sequelae of fractures also causes a higher incidence rate of osteoarthritis and skeletal deformities, predisposing the patient to chronic pain [3].…”

Section: Introductionmentioning

confidence: 99%

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Physical function in UK adults with osteogenesis imperfecta: a cross-sectional analysis of the RUDY study

et al. 2020

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We describe physical function in adults with osteogenesis imperfecta (OI) and explored clinical and non-clinical factors related to its impairment. Our data showed that physical dysfunction is a common feature of adults with OI, varying by OI severity, and mediated by the presence and quality of pain and fatigue symptoms.Introduction There is a paucity of data describing physical function in adults with Osteogenesis imperfecta (OI). We investigated the effects of OI and its severity on physical function, and explored the relationship between physical function and number of fractures and symptomatology.Methods Adults with OI of different types were recruited from the RUDY study, an ongoing UKbased prospective cohort study. Participants completed demographic and clinical questions, and questionnaires. These assessed physical function (SF-36), mobility (EQ-5D-5L and NEADL), fatigue (FACIT-F) and pain (SF-MQ-2). Scores were compared using parametric or non-parametric statistical analyses, whereas correlations between outcomes were examined using univariate and multivariate regression analysis.Results Seventy-eight adults with OI aged 43.5±14.5 years were enrolled (type I, 32; type III, 11; type IV, 10; unknown type, 26). Physical function (PCS, SF-36) was significantly lower in all participants than normative values (p<0.001) and in type III than type I (p=0.008). Mobility was significantly different across the types (EQ-5D-EL, p=0.007; NEADL, p<0.001), with type III having more severe problems, followed by types IV, unknown and I. Physical function was associated with OI type (r=0.26; p=0.021), presence and quality of pain (r=-0.57; p<0.0001) and fatigue (r=-0.51; p<0.0001). Multivariate analysis revealed that physical function correlated independently with age, OI type, fatigue and non-neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Physical function in UK adults with osteogenesis imperfecta: a cross-sectional analysis of the RUDY study

et al. 2020

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“…These patients show bone fragility, deformities of long bones, and short stature. The bone brittleness results in fractures even after minor trauma and subsequent growth restriction [ 3 ]. The clinical classification of OI was first established by Sillence and colleagues in 1979 [ 4 ] and five clinical forms are defined in the revised “Nosology and Classification of Genetic Skeletal Disorders.” [ 5 ] OI type Ⅰ has the mildest phenotype while type Ⅳ is a moderately severe form.…”

Section: Introductionmentioning

confidence: 99%

Association of trabecular bone score and bone mineral apparent density with the severity of bone fragility in children and adolescents with osteogenesis imperfecta: A cross-sectional study

Ohata,

Kitaoka,

Ishimi

et al. 2023

PLoS ONE

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Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray absorptiometry (DXA), is used to assess bone brittleness. The height-adjusted BMD Z-score (BMDHAZ) is calculated in children and adolescents with OI to reduce the confounding factor of short stature. However, even with the BMDHAZ, severity evaluation in children and adolescents with OI is challenging because certain abnormalities in bone quality cannot be accurately assessed by BMD analysis. The trabecular bone scores (TBS) and bone mineral apparent density (BMAD), which represent the structural integrity of bone and bone-size-associated BMD, respectively, are associated with fracture risk. Recently, age- and sex-specific reference ranges have been reported, enabling the calculation of Z-scores for children. To evaluate which density measurements show the highest correlation with fracture risk, we analyzed the associations between the Z-scores of TBS, BMAD, and BMDHAZ, fracture rate, and genetic variants. We retrospectively reviewed 42 participants with OI aged 5 to 20 years who underwent DXA. COL1A1/2 pathogenic variants were detected in 41 of the 42 participants. In participants with nonsense and frameshift variants (n = 17) resulting in haploinsufficiency and mild phenotype, the TBS Z-score was negatively correlated with fracture rate (FR) (r = -0.50, p = 0.042). In participants with glycine substitution (n = 9) causing the severe phenotype, the BMAD Z-scores were negatively correlated with FR (r = -0.74, p = 0.022). No correlation between the BMDHAZ and FR was observed in both groups. These findings suggest that the TBS and BMAD are useful in assessing children and adolescents with OI with specific genetic variants.

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Comprehensive genetic analyses using targeted next-generation sequencing and genotype-phenotype correlations in 53 Japanese patients with osteogenesis imperfecta

et al. 2019

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To elucidate mutation spectrum and genotype-phenotype correlations in Japanese patients with OI, we conducted comprehensive genetic analyses using NGS, as this had not been analyzed comprehensively in this patient population. Most mutations were located on COL1A1 and COL1A2. Glycine substitutions in COL1A1 resulted in the severe phenotype. Introduction Most cases of osteogenesis imperfecta (OI) are caused by mutations in COL1A1 or COL1A2, which encode α chains of type I collagen. However, mutations in at least 16 other genes also cause OI. The mutation spectrum in Japanese patients with OI has not been comprehensively analyzed, as it is difficult to identify using classical Sanger sequencing. In this study, we aimed to reveal the mutation spectrum and genotype-phenotype correlations in Japanese patients with OI using next-generation sequencing (NGS). Methods We designed a capture panel for sequencing 15 candidate OI genes and 19 candidate genes that are associated with bone fragility or Wnt signaling. Using NGS, we examined 53 Japanese patients with OI from unrelated families. Results Pathogenic mutations were detected in 43 out of 53 individuals. All mutations were heterozygous. Among the 43 individuals, 40 variants were identified including 15 novel mutations. We found these mutations in COL1A1 (n = 30, 69.8%), COL1A2 (n = 12, 27.9%), and IFITM5 (n = 1, 2.3%). Patients with glycine substitution on COL1A1 had a higher frequency of fractures and were more severely short-statured. Although no significant genotype-phenotype correlation was observed for bone mineral density, the trabecular bone score was significantly lower in patients with glycine substitutions. Conclusion We identified pathogenic mutations in 81% of our Japanese patients with OI. Most mutations were located on COL1A1 and COL1A2. This study revealed that glycine substitutions on COL1A1 resulted in the severe phenotype among Japanese patients with OI.

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Osteogenesis Imperfecta

Cited by 4 publications

References 52 publications

Physical function in UK adults with osteogenesis imperfecta: a cross-sectional analysis of the RUDY study

Physical function in UK adults with osteogenesis imperfecta: a cross-sectional analysis of the RUDY study

Association of trabecular bone score and bone mineral apparent density with the severity of bone fragility in children and adolescents with osteogenesis imperfecta: A cross-sectional study

Comprehensive genetic analyses using targeted next-generation sequencing and genotype-phenotype correlations in 53 Japanese patients with osteogenesis imperfecta

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