The Creation of an Individualized School Plan for Optimal Inclusion of Students with Osteogenesis Imperfecta.

AIMS: The aims of this study were to: (1) synthesize existing evidence regarding the integration of students with osteogenesis imperfecta (OI) into the school setting, (2) tabulate existing school integration tools for OI, and (3) create an individualized school plan to facilitate school integration. METHODS: Guided by the process of developing evidence-informed guidelines, an international, interprofessional, expert task force was convened. The process entailed: (1) reviewing of the literature, (2) developing recommendations, and (3) creating a clinically meaningful, person-focused plan to facilitate the integration and promotion of school inclusivity. The 13-member task force relied on empirical studies, grey literature, and their experiential knowledge (from clinical, teaching or patient experiences) to devise the plan. RESULTS: Over a series of eight meetings and five drafts, the Task Force prioritized 14 core items for inclusion. These items consisted of general student information, fracture response protocol, student inclusion recommendations, mobility considerations, transfer considerations, toileting protocol, physical education recommendations, fieldtrip information, transportation considerations, evacuation plan, environmental and scholarly considerations, consent and authorization, and an annual renewal document. CONCLUSION: Further research is recommended to pilot the plan, solicit ongoing feedback, implement and evaluate the plan into routine education and health care practices.

Recommendations for High-resolution Peripheral Quantitative Computed Tomography Assessment of Bone Density, Microarchitecture, and Strength in Pediatric Populations.

PURPOSE OF REVIEW: The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT). RECENT FINDINGS: Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each. Limiting protocol variation will enhance the uniformity of results and increase our ability to compare study results between different research groups. We outline special cases along with tips and tricks for acquiring and processing scans to minimize motion artifacts and account for growing bone. The recommendations in this review are intended to help researchers perform HR-pQCT imaging in pediatric populations and extend our collective knowledge of bone structure, architecture, and strength during the growing years.

Genetic factors contributing to late adverse musculoskeletal effects in childhood acute lymphoblastic leukemia survivors.

BACKGROUND: A substantial number of survivors of childhood acute lymphoblastic leukemia (ALL) suffer from treatment-related late adverse effects. While multiple studies have identified the effects of chemotherapeutics and radiation therapy on musculoskeletal outcomes, few have investigated their associations with genetic factors. METHODS: Here we analyzed musculoskeletal complications in relation to common and rare genetic variants derived through whole-exome sequencing of the PETALE cohort. Top-ranking associations were further assessed through stratified and multivariate analyses. RESULTS: DUOX2 variant was associated with skeletal muscle function deficit, as defined by peak muscle power Z score ≤ -2 SD (P = 4.5 × 10-5 for genotyping model). Upon risk stratification analysis, common variants in the APOL3, COL12A1, and LY75 genes were associated with Z score ≤ -2 SD at the cross-sectional area (CSA) at 4% radial length and lumbar bone mineral density (BMD) in high-risk patients (P ≤ 0.01). The modulation of the effect by risk group was driven by the interaction of the genotype with cumulative glucocorticoid dose. Identified variants remained significant throughout multivariate analyses incorporating non-genetic factors of the studied cohort. CONCLUSION: This exploratory study identified novel genetic variants associated with long-term musculoskeletal impairments in childhood ALL survivors. Replication in an independent cohort is needed to confirm the association found in this study.

Craniocervical abnormalities in osteogenesis imperfecta type V.

Craniocervical abnormalities in osteogenesis imperfecta (OI) such as basilar invagination or cervical kyphosis can cause severe neurological morbidity. These abnormalities may be more frequent in OI type V compared with other OI subtypes of similar disease severity, underlining the importance of screening in this group. INTRODUCTION: Craniocervical abnormalities in osteogenesis imperfecta (OI) can cause severe neurological morbidity. Although radiological cranial base abnormalities in OI have been well described in the literature, there are limited data on these abnormalities in OI type V and their association with clinical sequelae. METHODS: A retrospective case series on patients with craniocervical abnormalities in OI type V at our institution. RESULTS: Craniocervical abnormalities were present in 7 of 37 patients with OI type V (19%). For 5 patients (age at last follow-up: 5 to 26 years; 2 females), sufficient information was available for inclusion in the case series. All had genetically confirmed OI type V. Age range at diagnosis of the craniocervical abnormality was 1 day to 18 years. Basilar invagination was present in 3 patients; 2 had cervical kyphosis. Dysplasia of upper cervical vertebrae or base of skull was seen in 3 patients. The severity of the craniocervical abnormality did not clearly correlate with the severity of the OI phenotype. Three patients required surgical intervention (ages 7, 11, and 26 years) due to compression of the spinal cord or brainstem. Craniocervical abnormalities were detected incidentally or on screening in 3 patients, and only 2 had significant positive findings on neurological examination. CONCLUSION: A variety of craniocervical abnormalities are seen in OI type V including dysplasia of the cervical vertebrae. These cases highlight the importance of screening patients with OI type V with lateral skull and cervical spine x-rays throughout childhood and after skeletal maturity.

Genotype and malocclusion in patients with osteogenesis imperfecta.

OBJECTS: To investigate the relationship between genotype and severity of malocclusion in osteogenesis imperfecta (OI). SETTING AND SAMPLE POPULATION: A total of 49 patients participated in this cross-sectional study (age range: 5-19 years; 28 females; diagnoses: OI type I, N = 7; OI type III, N = 11; OI type IV, N = 27; OI type V, N = 2; OI type VI, N = 2). MATERIALS AND METHODS: Sequence analysis of COL1A1/COL1A2 and other OI-related genes was compared to the Peer Assessment Rating (PAR), an index reflecting the severity of malocclusion. RESULTS: The mutation spectrum was as follows: COL1A1, N = 22; COL1A2, N = 22, IFITM5, N = 2; SERPINF1, N = 2; no mutation detected, N = 1). Compared to patients with COL1A1 mutations, patients with COL1A2 mutations had significantly higher scores for total PAR, anterior cross-bite, anterior open bite and anteroposterior buccal occlusion. Males with COL1A2 mutations had significantly higher total PAR scores than females (median 36 vs 30, P = .047, Mann-Whitney test). Exploratory correlation between age and buccal vertical occlusion was noted in patients with COL1A2 mutations (Spearman correlation: r = .46, P = .03, power = .50). Two patients with OI type V (caused by IFITM5 mutations) had total PAR scores of 44 and 21. Both patients scored high for "segment." Patients with OI type VI (due to SERPINF1 mutations) scored similar to OI type V for "centreline." Considerable difference was observed in the total PAR score between the 2 patients with OI type VI. They had total PAR of 43 and 2. CONCLUSION: Type of disease-causing mutation affects the severity of malocclusion in individuals with OI.

Molecular diagnosis in children with fractures but no extraskeletal signs of osteogenesis imperfecta.

In 26 of 94 individuals (28%) below 21 years of age who had a significant fracture history but did not have extraskeletal features of osteogenesis imperfecta (OI), we detected disease-causing mutations in OI-associated genes. INTRODUCTION: In children who have mild bone fragility but do not have extraskeletal features of OI, it can be difficult to establish a diagnosis on clinical grounds. Here, we assessed the diagnostic yield of genetic testing in this context, by sequencing a panel of genes that are associated with OI. METHODS: DNA sequence analysis was performed on 94 individuals below 21 years of age who had a significant fracture history but had white sclera and no signs of dentinogenesis imperfecta. RESULTS: Disease-causing variants were detected in 28% of individuals and affected 5 different genes. Twelve individuals had mutations in COL1A1 or COL1A2, 8 in LRP5, 4 in BMP1, and 2 in PLS3. CONCLUSIONS: DNA sequence analysis of currently known OI-associated genes identified disease-causing variants in more than a quarter of individuals with a significant fracture history but without extraskeletal manifestations of OI.

Long-term follow-up in osteogenesis imperfecta type VI.

This retrospective study on long-term outcomes in osteogenesis imperfecta type VI found that patients who received intravenous bisphosphonate treatment had an increase in lumbar spine areal bone mineral density, a higher final height z-score, and some reshaping of vertebral bodies. INTRODUCTION: Osteogenesis imperfecta (OI) type VI is an ultra-rare bone fragility disorder caused by recessive mutations in SERPINF1. Here, we describe long-term outcomes in OI type VI and compare the clinical phenotypes caused by different types of SERPINF1 mutations. METHODS: This study includes a retrospective chart review of 13 individuals with OI type VI. RESULTS: In the absence of therapy, lumbar spine areal bone mineral density (BMD) did not increase during childhood and longitudinal growth seemed to stall after the age of 6 to 8 years. The phenotype was similar between individuals with different types of SERPINF1 mutations. Intravenous bisphosphonate treatment was associated with an increase in lumbar spine areal BMD and some reshaping of compressed vertebral bodies. Patients who had started bisphosphonate treatment early (before the age of 6 years) were taller than patients who had received bisphosphonate treatment later during their growing years. Lower extremity fractures were frequent despite bisphosphonate treatment and scoliosis was present in all patients who had reached the final height. Most patients had restricted mobility. In four patients, intravenous bisphosphonate treatment was eventually substituted by subcutaneous injections of denosumab, without clear changes in the clinical picture. CONCLUSIONS: Patients with OI type VI who received intravenous bisphosphonate treatment during growth had an increase in lumbar spine areal BMD, a higher final height z-score, and presented some reshaping of vertebral bodies. More effective treatment modalities are clearly required in OI type VI.

Musculoskeletal health in newly diagnosed children with Crohn's disease.

We evaluated the impact of Crohn's disease on muscle and bone strength, mass, density, and geometry in children with newly diagnosed CD and found profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low. INTRODUCTION: Crohn's disease (CD) is an inflammatory condition of the gastrointestinal tract that can affect the musculoskeletal system. The objective of this study was to determine the prevalence of vertebral fractures and the impact of CD on muscle and bone mass, strength, density, and geometry in children with newly diagnosed CD. METHODS: Seventy-three children (26 girls) aged 7.0 to 17.7 years were examined within 35 days following CD diagnosis by lateral spine radiograph for vertebral fractures and by jumping mechanography for muscle strength. Bone and muscle mass, density, and geometry were assessed by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography (pQCT). RESULTS: Disease activity was moderate to severe in 66 (90%) patients. Mean height (Z-score -0.3, standard deviation (SD) 1.1, p = 0.02), weight (Z-score -0.8, SD 1.3, p < 0.01), body mass index (Z-score -1.0, SD 1.3, p < 0.01), lumbar spine areal bone mineral density (BMD; Z-score -1.1, SD 1.0, p < 0.01), total body bone mineral content (Z-score -1.5, SD 1.0, p < 0.01), and total body lean mass (Z-score -2.5, SD 1.1, p < 0.01) were all low for age and gender. pQCT showed reduced trabecular volumetric BMD at the tibial metaphysis, expansion of the bone marrow cavity and thin cortices at the diaphysis, and low calf muscle cross-sectional area. Jumping mechanography demonstrated low muscle power. Only one patient had a vertebral fracture. CONCLUSIONS: Children with newly diagnosed CD have profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low.

Muscle abnormalities in osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI. Muscle mass is decreased in OI, even when short stature is taken into account. Dynamic muscle tests aiming at maximal eccentric force production reveal functional deficits that can not be explained by low muscle mass alone. However, it appears that diaphyseal bone mass is normally adapted to muscle force. At present the determinants of muscle mass and function in OI have not been clearly defined. Physiotherapy interventions and bisphosphonate treatment appear to have some effect on muscle function in OI. Interventions targeting muscle mass have shown encouraging results in OI animal models and are an interesting area for further research.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. METHODS: We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. CONCLUSION: Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.

Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment.

Osteogenesis imperfecta (OI) is the most prevalent heritable bone fragility disorder in children. It has been known for three decades that the majority of individuals with OI have mutations in COL1A1 or COL1A2, the two genes coding for collagen type I alpha chains, but in the past 10 years defects in at least 17 other genes have been linked to OI. Almost all individuals with a typical OI phenotype have a mutation in one of the currently known genes. Regarding medical treatment, intravenous bisphosphonate therapy is the most widely used medical approach. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures, but there is little effect of bisphosphonate therapy on the development of scoliosis. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. Newer medications with anti-resorptive and bone anabolic action are being investigated in an attempt to improve on the efficacy of bisphosphonates but the safety and efficacy of these new approaches in children with OI is not yet established.

DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum.

We detected disease-causing mutations in 585 of 598 individuals (98 %) with typical features of osteogenesis imperfecta (OI). In mild OI, only collagen type I encoding genes were involved. In moderate to severe OI, mutations in 12 different genes were found; 11 % of these patients had mutations in recessive genes. INTRODUCTION: OI is usually caused by mutations in COL1A1 or COL1A2, the genes encoding collagen type I alpha chains, but mutations in at least 16 other genes have also been associated with OI. It is presently unknown what proportion of individuals with clinical features of OI has a disease-causing mutation in one of these genes. METHODS: DNA sequence analysis was performed on 598 individuals from 487 families who had a typical OI phenotype. OI type I was diagnosed in 43 % of individuals, and 57 % had moderate to severe OI, defined as OI types other than type I. RESULTS: Disease-causing variants were detected in 97 % of individuals with OI type I and in 99 % of patients with moderate to severe OI. All mutations found in OI type I were dominant and exclusively affected COL1A1 or COL1A2. In moderate to severe OI, dominant mutations were found in COL1A1/COL1A2 (77 %), IFITM5 (9 %), and P4HB (0.6 %). Mutations in one of the recessive OI-associated gene were observed in 12 % of individuals with moderate to severe OI. The genes most frequently involved in recessive OI were SERPINF1 (4.0 % of individuals with moderate to severe OI) and CRTAP (2.9 %). CONCLUSIONS: DNA sequence analysis of currently known OI-associated genes identifies disease-causing variants in almost all individuals with a typical OI phenotype. About 20 % of individuals with moderate to severe OI had mutations in genes other than COL1A1/COL1A2.

Quality of life in osteogenesis imperfecta: A mixed-methods systematic review.

Clinical interventions and research have mostly focused on the orthopedic, genetic, and pharmacological outcomes of individuals with osteogenesis imperfecta (OI), and although quality of life (QoL) has gained recognition as an important patient-outcome, it has received little attention in individuals with OI. This mixed-methods systematic review of the literature included five search engines and identified a total of 212 articles. Once study eligibility was reviewed, 10 studies met the inclusion criteria and were included in this mixed-methods review (9 quantitative and 1 qualitative). Among the 10 included QoL studies, six reported on children with OI, three on adults with OI, and one on the parents of children with OI. Physical QoL in children and adults with OI appears to be less than that of the general population, with individuals with more severe OI types reporting worse QoL. On the other hand, mental and psychosocial QoL is the same or better in individuals with OI than that of the general population. Pain, scoliosis activity limitations and participation restrictions due to decreased function are associated with lower levels of physical QoL. Researchers must agree on a definition of QoL as it relates to OI and use validated measures appropriate for evaluating QoL in OI. Pediatric studies should consider both the child and the parent's QOL perceptions as these may differ. QoL in the adult population should not be dismissed in order to offer proper client-centered interventions throughout the lifespan.

Pediatric data for dual X-ray absorptiometric measures of normal lumbar bone mineral density in children under 5 years of age using the lunar prodigy densitometer.

OBJECTIVES: Knowledge of physiological variations of bone mineral density (BMD) in newborns and infants is necessary to evaluate pathological changes associated with fractures. Limited reference data for children under 5 years old are available. This study provides normative data of lumbar BMD for the Lunar Prodigy in young children under 5 years old. SUBJECTS AND METHODS: We assessed cross-sectionally 155 healthy children (77 boys, 80% Caucasian), ranging in age from newborn to the age of 5 years. Lumbar bone mineral content (BMC) and areal BMD were measured by dual-energy X-ray absorptiometry using a Lunar Prodigy absorptiometer. Volumetric BMD was calculated using the Kroeger and Carter methods. RESULTS: BMC and areal BMD increased from birth to 5 years (p<0.001). Volumetric BMD did not change with age. BMD and BMC correlated with age, weight and height (R(2)≥0.85 for all), with a maximum gain between the ages of 1 and 4 years, which did not follow the same pattern as height velocity. We did not find significant sex difference for any of the three measured parameters. CONCLUSION: This study provides normative data for lumbar spine densitometry of infants and young children using the Lunar Prodigy DXA system.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

Physical activity in youth with osteogenesis imperfecta type I.

INTRODUCTION: Individuals with Osteogenesis Imperfecta (OI) type I often show muscular weakness. However, it is unclear whether muscular weakness is a consequence of physical inactivity or a result of the disease itself. The aim was to assess muscle function in youth with OI type I and evaluate physical activity (PA). METHODS: Fourteen children with OI type I (mean age [SD]: 12.75 [4.62] years) were compared to 14 age- and gender-matched controls (mean age [SD]: 12.75 [4.59] years). Muscle force and power were determined through mechanography. PA and daily energy expenditure were measured with an accelerometer and a questionnaire. RESULTS: Compared to controls, children with OI type I had lower muscle force and power. OI type I children were as active as their healthy counterparts. CONCLUSIONS: Children and adolescents with OI type I and their healthy counterparts did not reached daily recommendations of PA. Given their muscle function deficit, youth with OI type I would benefit to reach these recommendations to prevent precocious effect of aging on muscles.

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome.

UNLABELLED: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. INTRODUCTION: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. METHODS: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. RESULTS: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017). CONCLUSIONS: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

The effect of systemic administration of sclerostin antibody in a mouse model of distraction osteogenesis.

Distraction osteogenesis (DO) is a successful technique for bone lengthening, but one problem is the need to keep an external fixator in place until bone completely regenerates. We hypothesized that the systemic administration of sclerostin antibodies (Scl-Ab) can accelerate bone regeneration in a mouse model of DO. A total of 110 mice were randomized to receive one intravenous injection per week of either Scl-Ab (100 mg per kg body weight) or saline after DO surgery. Mice were sacrificed on day 11, 17, 34 or 51 post-surgery. Microcomputed tomography showed that bone volume per tissue volume of the Scl-Ab treated group was significantly higher on day 11 (P=0.009). Histological examinations indicated that chondrocytes and fibrocartilage predominated in the Scl-Ab group at day 11. The radiographic score of bone healing was also higher in Scl-Ab treated animals at day 11. There was a trend towards higher ultimate force and work to failure in Scl-Ab treated groups on day 34 and 51 (P>0.05). These data suggest the potential utility of Scl-Ab to reduce the time during DO when an external fixator is required.

Validity of an accelerometer as a vertical ground reaction force measuring device in healthy children and adolescents and in children and adolescents with osteogenesis imperfecta type I.

INTRODUCTION: Vertical ground reaction forces (vGRFs) are closely related to bone strength and development. It is therefore relevant to assess these forces in bone disorders accompanied with muscle weakness such as in osteogenesis imperfecta type I (OI type I). The purpose of the present study was to assess the validity of vGRFs derived from an accelerometer. METHODS: Fourteen children and adolescents with a diagnosis of OI type I (age range: 7 to 21; mean age [SD]: 14.1 [4.8] years; 5 males) and fourteen healthy controls (age range: 6 to 21; mean age [SD]: 12.5 [4.2] years; 5 males) performed three repetitions of five different jump and rise tests on a ground reaction force plate. Jumps and rises outcomes were measured simultaneously with the ground reaction force plate and an accelerometer. RESULTS: Pearson correlation coefficients were over 0.96 (p<0.001) for the five tests. The limits of agreement represented between 17 and 31% of the average peak force measured by both devices. The accelerometer is a promising tool to assess ground reaction forces in everyday life settings and has been shown to be sufficiently sensitive to detect muscular weakness in children and adolescent with OI type I.