Osteogenesis Imperfecta Group Research Articles

Bone dysplasias in 1.6 million births in Argentina

Currently accepted birth prevalence for osteochondrodysplasias (OCDs) is about 2 per 10,000 births. Our main goal is to estimate the prevalence of OCDs in Argentina and compare it with other surveillance systems. We examined 1,663,610 births among 160 hospitals of RENAC (Red Nacional de Anomalías Congénitas - National Network of Congenital Anomalies) between November 2009 and December 2016. Cases were detected and registered according to a pre-established protocol, ranked in three diagnostic evidence levels according to available clinical documentation, and categorized according to the 9th edition of the nosology and classification of genetic skeletal disorders. Within our dataset, the most frequent groups were Group-1 (FGFR3, chondrodysplasia) and Group-25 (Osteogenesis Imperfecta and decreased bone density). Birth prevalence per 10,000 for the main OCD types, were: Achondroplasia 0.47 (95% CI: 0.38–0.59), Thanatophoric Dysplasia 0.37 (95% CI: 0.29–0.48), and the Osteogenesis Imperfecta group 0.34 (95% CI: 0.26–0.44). For total OCD, birth prevalence was 2.20 per 10.000 births (95% CI: 1.98–2.44). RENAC prevalence of total OCDs was found to be lower than that reported by the Latin-American Study of Congenital Malformations (ECLAMC) and Utah Birth Defect Network but higher than EUROCAT. Our investigation is the first study of OCD prevalence in Argentina using data from every jurisdiction of the country.

How good are we in predicting the risk of infant mortality for newborns undergoing “curative” surgery for structural congenital heart defects? A prospective, population-based cohort (EPICARD) study

Currently accepted birth prevalence for osteochondrodysplasias (OCDs) is about 2 per 10,000 births. Our main goal is to estimate the prevalence of OCDs in Argentina and compare it with other surveillance systems. We examined 1,663,610 births among 160 hospitals of RENAC (Red Nacional de Anomalías Congénitas - National Network of Congenital Anomalies) between November 2009 and December 2016. Cases were detected and registered according to a pre-established protocol, ranked in three diagnostic evidence levels according to available clinical documentation, and categorized according to the 9th edition of the nosology and classification of genetic skeletal disorders. Within our dataset, the most frequent groups were Group-1 (FGFR3, chondrodysplasia) and Group-25 (Osteogenesis Imperfecta and decreased bone density). Birth prevalence per 10,000 for the main OCD types, were: Achondroplasia 0.47 (95% CI: 0.38–0.59), Thanatophoric Dysplasia 0.37 (95% CI: 0.29–0.48), and the Osteogenesis Imperfecta group 0.34 (95% CI: 0.26–0.44). For total OCD, birth prevalence was 2.20 per 10.000 births (95% CI: 1.98–2.44). RENAC prevalence of total OCDs was found to be lower than that reported by the Latin-American Study of Congenital Malformations (ECLAMC) and Utah Birth Defect Network but higher than EUROCAT. Our investigation is the first study of OCD prevalence in Argentina using data from every jurisdiction of the country.

Gait Deviations in Children With Osteogenesis Imperfecta Type I.

Osteogenesis imperfecta (OI) is a congenital connective tissue disorder often characterized by orthopaedic complications that impact normal gait. As such, mobility is of particular interest in the OI population as it is associated with multiple aspects of participation and quality of life. The purpose of the current study was to identify and describe common gait deviations in a large sample of individuals with type I OI and speculate the etiology with a goal of improving function. Gait analysis was performed on 44 subjects with type I (11.7±3.08 y old) and 30 typically developing controls (9.54±3.1 y old ). Spatial temporal, kinematic, and kinetic gait data were calculated from the Vicon Plug-in-Gait Model. Musculoskeletal modeling of the muscle tendon lengths (MTL) was done in OpenSim 3.3 to evaluate the MTL of the gastrocnemius and gluteus maximus. The gait deviation index, a dimensionless parameter that evaluates the deviation of 9 kinematic gait parameters from a control database, was also calculated. Walking speed, single support time, stride, and step length were lower and double support time was higher in the OI group. The gait deviation index score was lower and external hip rotation angle was higher in the OI group. Peak hip flexor, knee extensor and ankle plantarflexor moments, and power generation at the ankle were lower in the OI group. MTL analysis revealed no significant length discrepancies between the OI group and the typically developing group. Together, these findings provide a comprehensive description of gait characteristics among a group of individuals with type I OI. Such data inform clinicians about specific gait deviations in this population allowing clinicians to recommend more focused interventions. Level III-case-control study.

Fracture Patterns Differ Between Osteogenesis Imperfecta and Routine Pediatric Fractures.

It is important to estimate the likelihood that a pediatric fracture is caused by osteogenesis imperfecta (OI), especially the least severe type of OI (type 1). We reviewed records of 29,101 pediatric patients with fractures from 2003 through 2015. We included patients with closed fractures not resulting from motor vehicle accidents, gunshot wounds, nonaccidental trauma, or bone lesions. Patients with OI of any type were identified through International Classification of Diseases-9 code. We randomly sampled 500 pediatric patients in whom OI was not diagnosed to obtain a control (non-OI) group. We reviewed age at time of fracture, sex, fracture type, laterality, and bone and bone region fractured. Bisphosphonate use and OI type were documented for OI patients. Subanalysis of patients with type-1 OI was performed. The Fisher exact and χ tests were used to compare fracture rates between groups. P<0.05 was considered significant. Positive likelihood ratios for OI were calculated by fracture pattern. The non-OI group consisted of 500 patients with 652 fractures. The OI group consisted of 52 patients with 209 fractures. Non-OI patients were older at the time of fracture (mean, 9.0±5.0 y) than OI patients (mean, 5.5±4.4 y) (P<0.001). OI patients had more oblique, transverse, diaphyseal, and bilateral long-bone fractures than non-OI patients (all P<0.001). Non-OI patients had more buckle (P=0.013), metaphyseal (P<0.001), and physeal (P<0.001) fractures than OI patients. For patients with type-1 OI and long-bone fractures (n=18), rates of transverse and buckle fractures were similar compared with controls. Transverse humerus (15.2), olecranon (13.8), and diaphyseal humerus (13.0) fractures had the highest positive likelihood ratios for OI, and physeal (0.09) and supracondylar humerus (0.1) fractures had the lowest. Transverse and diaphyseal humerus and olecranon fractures were most likely to indicate OI. Physeal and supracondylar humerus fractures were least likely to indicate OI. Radiographic fracture pattern is useful for estimating likelihood of OI. Level III.

Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta

Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32–65% lower in the OI group (p<0.001). Yield strain did not differ between groups (p≥0.197). In both groups, modulus and strength were lower in the transverse direction (p≤0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p<0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p=0.086). Volumetric bone mineral density was lower in the OI group (p<0.001), but volumetric tissue mineral density was not (p=0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p≤0.024) but not volumetric tissue mineral density (p≥0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI.

Static Postural Control in Youth With Osteogenesis Imperfecta Type I

ObjectivesTo assess static postural control in eyes-open and eyes-closed conditions in individuals with osteogenesis imperfecta (OI) type I as compared with typically developing (TD) individuals and to explore the relation between postural control and lower limb muscle function. DesignCross-sectional study. SettingOutpatient department of a pediatric orthopedic hospital. ParticipantsA convenience sample (N=38) of individuals with OI type I (n=22; mean age, 13.1y; range, 6–21y) and TD individuals (n=16; mean age, 13.1y; range, 6–20y) was selected. Participants were eligible if they were between 6 and 21 years and if they did not have any fracture or surgery in the lower limb in the 12 months before testing. InterventionsNot applicable. Main Outcomes MeasuresPostural control was assessed through static balance tests and muscle function through mechanographic tests on a force platform. Selected postural parameters were path length, velocity, 90% confidence ellipse area, and the ellipse's length of the mediolateral and anteroposterior axes. Mechanographic parameters were peak force and peak power as measured using the multiple two-legged hopping and the single two-legged jump test, respectively. ResultsIndividuals with OI type I had poorer postural control than did TD individuals as indicated by longer and faster displacements and a larger ellipse area. Muscle function was unrelated to postural control in the OI group. Removing visual information resulted in a larger increase in postural control parameters in the OI group than in the TD group. ConclusionsA proprioceptive deficit could explain poorer postural control in individuals with OI type I.

Occlusal features and need for orthodontic treatment in persons with osteogenesis imperfecta.

The aim of the study was to (a) analyse dental occlusion and determine the need for orthodontic treatment of persons with osteogenesis imperfecta (OI) in comparison with the healthy population and (b) investigate the associations between OI and malocclusion. A case‐control study included 26 OI persons and 400 healthy participants (control group). Occlusal features and the need for orthodontic treatment were defined according to Dental Health Component‐Index of Orthodontic Treatment Need and Dental Aesthetic Index. Results showed that Angle Class I, II, and III relationship was found in 23.1%, 3.8%, and 73.1% of OI group, and in the control group, it was 67%, 17.5%, and 15.5%, respectively. OI group had significantly higher prevalence of reverse overjet >1 mm (76.9%), missing teeth (42.3%), posterior crossbite (34.6%), and open bite >2 mm (19.2%) compared to the control group (8.5%, 2.2%, 6.2%, and 3.5%, respectively). OI group had less incisal segment crowding and more incisal segment spacing than the control group (p < 0.05). The need for orthodontic treatment of OI group according to Dental Health Component‐Index of Orthodontic Treatment Need and Dental Aesthetic Index was 88.5% and 61.5%, respectively, while in the control group, it was 24.8% and 51.8%. The malocclusion in OI persons was associated with reverse overjet > 1 mm (OR = 13.3, 95% CI = 3.9–44.7, p < .001), Angle Class III malocclusion (OR = 8.0, 95% CI = 2.0–30.8, p = .003), and missing teeth (OR = 4.7, 95% CI = 1.0–22.4, p = .049). In conclusion, there is the high probability of malocclusion in OI persons. Persons with OI require early orthodontic treatment because of significant correlation of OI disease with Angle Class III malocclusion, reverse overjet, and missing teeth.

Timing of dental development in osteogenesis imperfecta patients with and without bisphosphonate treatment

Bisphosphonates have established their role as medical therapy for pediatric osteogenesis imperfecta (OI) patients. Since bisphosphonates have also been shown to delay tooth development in animal models, we aimed to assess whether the medication has a similar effect on children with OI. In this cross-sectional study, bisphosphonate-treated OI patients of whom dental panoramic tomograph was taken between 3 and 16years of age formed the study group. The patients, 22 in total, had been treated with pamidronate, zoledronic acid or risedronate for at least one year before the radiography. Developmental stage of the permanent teeth, resorption of the deciduous teeth, and number of the erupted permanent teeth were radiographically assessed in the left mandibular quadrant. Dental panoramic tomographs of 50 OI patients, naïve to bisphosphonates, and of 50 healthy individuals of the same age were used as controls. The dental development was statistically significantly accelerated in the OI group naïve to bisphosphonates showing median advancement of dental age by 0.63years from chronological age and median increase in the number of erupted teeth by 0.31 as compared to Finnish norms. Bisphosphonate-treated OI patients displayed, however, age-appropriate dental development. The OI patients not treated with bisphosphonates also showed statistically significantly faster resorption of the deciduous teeth than the treated ones, and displayed an altered interrelationship between the resorption stage of an individual primary tooth and the developmental stage of the succedaneous permanent tooth, unlike the OI patients treated with bisphosphonate. No correlation between either cumulative bisphosphonate dose or between treatment length and any measured component of the dental development was found. To conclude, OI itself was found to lead to advanced dental development. Bisphosphonate treatment had a delaying effect in all the three aspects studied, resulting in a rate of dental development indistinguishable from normal.

Multiparametric Classification of Skin from Osteogenesis Imperfecta Patients and Controls by Quantitative Magnetic Resonance Microimaging.

The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI) to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI) and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected) and nine OI patients were imaged to generate maps of five separate MR parameters, T1, T2, km, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T2 and km. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI.

Echocardiographic Evidence of Early Diastolic Dysfunction in Asymptomatic Children with Osteogenesis Imperfecta

Structural and functional cardiovascular abnormalities have been reported in adults with osteogenesis imperfecta (OI); however, there is a lack of paediatric literature on this topic. This study aimed to investigate cardiovascular abnormalities in children with OI in comparison to a control group. This case-control study was conducted at the Sultan Qaboos University Hospital in Muscat, Oman, between May 2013 and August 2014. Data from eight patients with OI and 24 healthy controls were compared using conventional and tissue Doppler echocardiography (TDE). The OI group had significantly lower peak early mitral valve flow velocity (P = 0.027), peak a-wave reversal in the pulmonary vein (P = 0.030) and peak early diastolic velocity of the mitral valve and upper septum (P = 0.001 each). The peak late diastolic velocities of the mitral valve (P = 0.002) and the upper septum (P = 0.037) were significantly higher in the OI group; however, the peak early/late diastolic velocity ratios of the mitral valve (P = 0.002) and upper septum (P = 0.001) were significantly lower. Left ventricular dimensions and aortic and pulmonary artery diameters were larger in the OI group when indexed for body surface area. Both groups had normal systolic cardiac function. Children with OI had normal systolic cardiac function. However, changes in myocardial tissue Doppler velocities were suggestive of early diastolic cardiac dysfunction. They also had increased left ventricular dimensions and greater vessel diameters. These findings indicate the need for early and detailed structural and functional echocardiographic assessment and follow-up of young patients with OI.

MRI‐based abnormalities in young adults at risk of adverse bone health due to childhood‐onset metabolic &amp; endocrine conditions

Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro-architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism. High-resolution micro-MRI images were acquired at the tibia using 3T MRI to calculate parameters of bone micro-architecture in seven adults with OI and 10 adults with endocrinopathies. MR Spectroscopy was performed in participants to calculate vertebral BMA, which was expressed as percentage fat fraction (%FF). Lumbar spine DXA was performed to assess bone mineral density. The MRI data were compared with a group of 22 healthy adults who were divided into two age-matched control groups. Intra-operator repeatability was high, with an average CoV of 1% for micro-MRI and 2·5% for MRS. The ratio of apparent bone volume to total volume (appBV/TV) in the endocrinopathy and OI groups was lower than in age-matched control groups (P = 0·003 and P = 0·008 respectively). A weak association between DXA BMD and appBV/TV was also observed (r = 0·5, P = 0·045). %FF was higher in the endocrinopathy group than in the age-matched control group (P = 0·005), but no difference in %FF was observed between the OI group and their age-matched control group (P = 0·26). MRI provides valuable detailed information on the micro-architecture and adiposity of bones and is capable of showing clear differences in bone parameters in a range of clinical conditions associated with abnormal bone health.

Mineral particle size in children with osteogenesis imperfecta type I is not increased independently of specific collagen mutations

Osteogenesis imperfecta (OI) type I represents the mildest form of OI and is usually caused by two classes of autosomal dominant mutations in collagen type I: haploinsufficiency leading to a reduced quantity of structurally normal collagen (quantitative mutation), or sequence abnormalities generating structurally aberrant collagen chains (qualitative mutation). An abnormally high bone matrix mineralization has been observed in all OI cases investigated so far, independently of mutation type. This raises the question whether the increased amount of mineral is due to mineral particles growing to larger sizes or to a higher number of more densely packed particles. For this reason, we revisit the problem by investigating the mineral particle size in cancellous bone from two subsets of the previously analyzed biopsies (patient's age: 2–4.2 and 7.6–11years) comparing OI quantitative mutations (n=5), OI qualitative mutations (n=5) and controls (n=6). We used a combined small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) setup with a beam diameter of 10μm of synchrotron radiation, which allows the determination of mineral particle characteristics in 10μm thick sections at the same positions where the matrix mineralization density was previously determined. The thickness parameter of mineral particles (T) was obtained from SAXS data and the mineral volume fraction was calculated from the mean calcium content of the bone matrix determined by quantitative back-scattered electron imaging (qBEI). The combination of these two quantities allowed calculating the true particle width (W) of the plate-like mineral crystals.T was larger in the older than in the younger age-group independently of genotype (p<0.004) and was larger in the controls than in each OI group. The qBEI results showed that the mineral volume fraction increased from 32.45wt.% in controls to 36.44wt.% in both OI groups (corresponding to a 12% increase in relative terms). Combining these data, we find that also W was larger in the older than in the younger age-group (p<0.002), but stayed equal or smaller in both OI genotypes (controls: 2.3nm±0.04, OI qualitative: 2.2±0.05; OI quantitative 2.3±0.04, mean±SEM). A linear regression analysis even suggests a slower increase of W in qualitative OI as compared to quantitative OI and controls, where the particle sizes stayed similar at all ages. We thus conclude that the high mineral density in human OI is not due to increased particle size but rather to increased particle packing density. The lack of an observed difference between the two classes of mutations suggests the occurrence of a bone cell defect downstream of the collagen mutation.

Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes

Osteogenesis imperfecta is a heritable disorder affecting bone and tooth development. Malocclusion is frequent in those affected by osteogenesis imperfecta, but this has not been studied in detail. The purpose of this study was to describe and quantify the severity of malocclusions in patients with osteogenesis imperfecta. Articulated dental casts were obtained from 49 patients diagnosed with osteogenesis imperfecta (ages 5-19 years; 28 female) and 49 age- and sex-matched control subjects who did not have osteogenesis imperfecta. Both groups were seeking orthodontic treatment. Malocclusions were scored by using the peer assessment rating (PAR) and the discrepancy index (DI). The average United Kingdom weighted PAR scores were 31.1 (SD, 14.5) for the osteogenesis imperfecta group and 22.7 (SD, 10.7) for the control group (P<0.05). The mean United States weighted PAR scores were 32.2 (SD, 15.0) for patients with osteogenesis imperfecta and 21.6 (SD, 9.6) for the controls (P<0.05). The average modified DI scores were 29.8 (SD, 20.2) for the osteogenesis imperfecta group and 12.4 (SD, 6.8) for the control group (P<0.05). Group differences were greatest for lateral open bite (osteogenesis imperfecta group, 7.1; control group, 0.3) for the DI parameters and anterior crossbite (osteogenesis imperfecta group, 13.0; control group, 3.8 [United Kingdom]) for the PAR. Both the PAR and the DI showed that malocclusions were significantly more severe in patients with osteogenesis imperfecta than in the control group. There was a higher incidence of Class III malocclusion associated with anterior and lateral open bites in patients affected by osteogenesis imperfecta.

Right Ventricular and Pulmonary Arterial Dimensions in Adults With Osteogenesis Imperfecta

We examined right ventricular (RV) and ascending pulmonary artery (PA1) dimensions in adults with osteogenesis imperfecta (OI). The survey included 99 adults with OI divided in 3 clinical types (I, III, and IV) and 52 controls. RV and PA1 dimensions were measured by echocardiography and indexed for body surface area. Scoliosis was registered, and spirometry was performed in 75 patients with OI. All RV dimensions indexed by body surface area were significantly larger in the OI group compared to controls (RV basal dimension 1.9 ± 0.5 vs 1.7 ± 0.3 cm/m(2), p <0.05; RV midcavity dimension 1.7 ± 0.5 vs 1.5 ± 0.3 cm/m(2), p <0.05; RV longitudinal dimension 4.3 ± 1.1 vs 4.0 ± 0.9 cm/m(2), p <0.05). RV outflow tract (RVOT) proximal diameter (1.8 ± 0.4 vs 1.5 ± 0.2 cm/m(2), p <0.05), RVOT distal diameter (1.2 ± 0.2 vs 1.0 ± 0.1 cm/m(2), p <0.05), and PA1 (1.2 ± 0.3 vs 1.0 ± 0.2 cm/m(2), p <0.05) were also significantly larger in the OI group. Furthermore, all RV dimensions and PA1 were significantly larger in patients with OI type III compared to patients with OI types I and IV and controls. There were no differences in RV, RVOT, or PA1 dimensions between patients presenting a restrictive ventilatory pattern (n = 11) and patients a normal ventilatory pattern. Scoliosis was registered in 42 patients. Patients with OI type III had greater RV and PA1 dimensions compared to controls and patients with OI types I and IV. Impaired ventilatory patterns and scoliosis did not have any impact on RV dimensions in these patients. In conclusion, patients with OI had increased RV and PA1 dimensions compared to the control group.

Cardiovascular abnormalities in adults with osteogenesis imperfecta

The aim of this study was to investigate cardiac abnormalities in adults with osteogenesis imperfecta (OI). The clinical and echocardiographic survey included 99 adults with OI divided into 3 clinical types-I, III, and IV-and 52 controls. Left ventricular end-diastolic dimensions (LVIDds), mass, and 4 aortic diameters were measured by standard echocardiography and indexed for body surface area. Hypertension was registered in 37 individuals (37.4%). The OI group had significantly lower body surface area than the control individuals, 1.7 ± 0.3 versus 1.9 ± 0.2 m(2) (P < .05). The LVIDd and LV mass were significantly larger in the OI group when compared with the controls, 2.98 ± .64 versus 2.59 ± .26 cm/m(2) (P < .05) and 97.3 ± 30.1 versus 73.3 ± 18.0 g/m(2) (P < .05), respectively. Type III OI showed significantly enlarged LVIDd as compared with types I and IV OI, 4.33 ± 1.10 versus 2.83 ± .33 (P < .05) versus 2.85 ± .37 cm/m(2) (P < .05), respectively. All aortic diameters were significantly larger in the OI group than in the control group, as they were in type III compared with types I and IV; 10.1% mild aortic regurgitation (AR), 10.1% moderate AR, and 7.1% moderate mitral regurgitation were registered in the OI group. Increased LVIDd, LV mass, mitral regurgitation, and AR were found in adult patients with OI compared with the control group. The changes in LV and dilatation of aorta seemed to be more pronounced in patients with type III compared with types I and IV OI.

Ankle Strength and Functional Limitations in Children and Adolescents With Type I Osteogenesis Imperfecta

To determine whether children with type I osteogenesis imperfecta (OI) exhibit ankle plantar flexor weakness and whether this correlates with physical function. Twenty children and adolescents with type I OI and 20 age-matched controls (age 6-18 years) participated in a single evaluation session. Data included strength assessment, Gillette Functional Assessment Questionnaire, Pediatric Outcome Data Collection Instrument (PODCI), and Faces Pain Scale-Revised. Ankle plantar flexor weakness was evident in the OI group compared with the control group. Heel-rise strength correlated with ankle isometric plantar flexion strength. Limitations in PODCI subscales-sports and physical function and pain/comfort-are present in the OI group. Ankle plantar flexor weakness is present in children and adolescents with type I OI and correlates with function. Gillette Functional Assessment Questionnaire, PODCI, and strength assessment are valuable evaluation tools for children and adolescents with type I OI and can aid therapists in goal setting.

Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations

Objective We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Patients and methods Sixty-four adult patients with OI (39% women, mean age ± SD: 37 ± 12 years) and 64 healthy age-matched controls (54% women, 39 ± 7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63 ± 8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62 ± 10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (α/β CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Results Patients with OI had CTX-II levels similar to those of subjects with knee OA ( p = 0.89; mean ± SEM; 460 ± 57 ng/mmol Cr for OI group and 547 ± 32 ng/mmol Cr for OA group) and significantly higher than both young (144 ± 7.8 ng/mmol Cr, p < 0.0001) and old controls (247 ± 7 ng/mmol Cr, p < 0.0001). In patients with OI, increased Helix-I ( p < 0.0001) and α/β CTX-I ( p = 0.0067) were independently associated with increased CTX-II and together explained 26% of its variance ( p < 0.0001). In patients with knee OA, increased levels of α/β CTX-I ratio were also associated with higher CTX-II levels. Conclusion Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA.

Gait characteristics and functional assessment of children with Type I Osteogenesis Imperfecta

The purpose of this study was to improve the evaluation process of children with type I Osteogenesis Imperfecta (OI) by providing a quantitative comparison of gait and selected functional assessments to age-matched controls. A 14-camera Vicon Motion Analysis System was used for gait analysis along with selected functional assessments (Pediatric Outcomes Data Collection Instrument [PODCI], Functional Assessment Questionnaire [FAQ], Faces Pain Scale-Revised [FPS-R]) conducted on 10 subjects with type I OI and 22 age-matched healthy controls. The results of the OI group demonstrated abnormal gait parameters including increased double support, delayed foot off, reduced ankle range of motion and plantarflexion during third rocker, along with greater ankle power absorption during terminal stance and reduced ankle power generation during push off. The functional assessment scores of the OI group were similar to the control group for basic mobility and function, but were lower than their peers in the sports and physical function category. The evaluation of individuals with OI by means of gait analysis and selected functional assessments, along with an accurate biomechanical model of the lower extremities, is proposed to better understand and predict OI disability and improve quality of life.

Bone densitometry in pediatric patients treated with pamidronate

Increasing numbers of children are being treated with the bisphosphonate pamidronate for low bone mineral density, particularly children with increased risk of fractures caused by bone disorders or low/non-weight bearing. To determine the effect of intravenous pamidronate on the bone mineral density of children with osteogenesis imperfecta and spastic quadriplegic cerebral palsy. Charts of 38 children with osteogenesis imperfecta (n=20) and spastic quadriplegic cerebral palsy (n=18) treated with pamidronate were retrospectively reviewed. Patients were selected for treatment because of prior fracture and/or abnormally low bone mineral density. All received intravenous pamidronate at two-month to eight-month intervals and were periodically examined using dual energy X-ray absorptiometry. All patients had abnormally low bone mineral density prior to treatment. Lumbar spine bone mineral density and z-scores showed serial improvement in 31 of 32 patients. Spine bone mineral density increased 78+/-38.1% in OI and 47.4+/-39.0% in children with cerebral palsy. The area of greatest lateral distal femur bone mineral density improvement was in the metaphysis adjacent to the growth plate, with a 96+/-87.8% improvement in the osteogenesis imperfecta group and 65.7+/-55.2% improvement in the cerebral palsy group. Increases in bone mineral density exceeded that expected for age-specific growth. This was demonstrated by improvement in both spine and femur z-scores for both groups. No children with spastic quadriplegic cerebral palsy experienced fractures after the first week of treatment, whereas patients with osteogenesis imperfecta continued to have fractures but at a decreased rate. Intravenous pamidronate given at 3- to 4-month intervals proved to be effective in increasing bone mineral density in patients with osteogenesis imperfecta and spastic quadriplegic cerebral palsy. The greatest gains in bone mineral density were observed in the children with osteogenesis imperfecta, but they did continue to fracture, albeit at a decreased rate. Children with cerebral palsy gained bone mineral density and did not continue to fracture.

The volumetric bone density and cortical thickness in adult patients affected by osteogenesis imperfecta.

In patients with osteogenesis imperfecta (OI), a disease characterized by abnormal bone fragility, bone mineral density (BMD) was found to be relatively preserved. Quantitative computed tomography (QCT) is the only available method for directly measuring in vivo both volumetric density and the cross-sectional area. Here we report the data from dual-energy X-ray absorptiometry DXA (spine and hip) and peripheral (pQCT) (ultradistal and proximal radius) measurement of 27 adult patients affected by OI, mostly of type I, compared with a group of healthy persons. In the patients with OI, areal BMD values at both femoral neck and lumbar spine were considerably lower than in control subjects (-32 and -36%, respectively; p<0.001 for body weight and height adjusted values). pQCT volumetric density at the ultradistal radius was 19% lower than in control subjects and this difference rose to 32% for purely cancellous bone tissue. The whole bone cross-sectional area of ultradistal radius, as measured by pQCT, was superimposable to normal. At the proximal radius, both cross-sectional area and cortical area, together with Bending Breaking Resistance Index (BBRI), were significantly lower in OI (-23; -22; -32% respectively; p<0.001 for body weight and height adjusted values), but cortical volumetric density was even slightly higher in the OI group than in control subjects. In conclusion, it appears that the most obvious defect in adults with OI is the inability to acquire an adequate thickness of the cortices of long bone and to achieve or maintain normal trabecular density.