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This study evaluated the accuracy of synthetic computed tomography (sCT), as compared to CT, for the 3D assessment of the hip morphology. Thirty male patients with asymptomatic hips, referred for magnetic resonance (MR) imaging and CT, were included in this retrospective study. sCT images were generated from three-dimensional radiofrequency-spoiled T1-weighted multi-echo gradient-echo MR images using a commercially available deep learning-enabled software and were compared with CT images through mean error and surface distance computation and by means of eight clinical morphometric parameters relevant for hip care. Parameters included center-edge angle (CEA), sharp angle, acetabular index, extrusion index, femoral head center-to-midline distance, acetabular version (AV), and anterior and posterior acetabular sector angles. They were measured by two senior orthopedic surgeons and a radiologist in-training on CT and sCT images. The reliability and agreement of CT- and sCT-based measurements were assessed using intraclass correlation coefficients (ICCs) for absolute agreement, Bland-Altman plots, and two one-sided tests for equivalence. The surface distance between CT- and sCT-based bone models were on average submillimeter. CT- and sCT-based measurements showed moderate to excellent interobserver and intraobserver correlation (0.56 0.75). For CEA, the intraobserver agreement was good (ICC > 0.75) and the interobserver agreement was moderate (ICC > 0.69). Limits of agreements were similar between intraobserver CT and intermodal measurements. All measurements were found statistically equivalent, with average intermodal differences within the intraobserver limits of agreement. In conclusion, sCT and CT were equivalent for the assessment of the hip joint bone morphology.

Semantic segmentation of bone from lower extremity computerized tomography (CT) scans can improve and accelerate the visualization, diagnosis, and surgical planning in orthopaedics. However, the large field of view of these scans makes automatic segmentation using deep learning based methods challenging, slow and graphical processing unit (GPU) memory intensive. We investigated methods to more efficiently represent anatomical context for accurate and fast segmentation and compared these with state-of-the-art methodology. Six lower extremity bones from patients of two different datasets were manually segmented from CT scans, and used to train and optimize a cascaded deep learning approach. We varied the number of resolution levels, receptive fields, patch sizes, and number of V-net blocks. The best performing network used a multi-stage, cascaded V-net approach with 128

Background and purpose: The Chiari osteotomy was a regular treatment for developmental hip dysplasia before it became mostly reserved as a salvage therapy. However, the long-term survival of the Chiari osteotomy has not been systematically investigated. We investigated the survival time of the Chiari osteotomy until conversion to total hip arthroplasty (THA) in patients with primary hip dysplasia, and factors which correlated with survival, complications, and the improvement measured in radiographic parameters.Patients and methods: Studies were included when describing patients (> 16 years) with primary hip dysplasia treated with a Chiari osteotomy procedure with 8 years’ follow-up. Data on patient characteristics, indications, complications, radiographic parameters, and survival time (endpoint: conversion to THA) were extracted.Results: 8 studies were included. The average postoperative center–edge angle, acetabular head index, and Sharp angle were generally restored within the target range. 3 studies reported Kaplan-Meier survival rates varying from 96% at 10 years to 72% at 20 years’ follow-up. Negative survival factors were high age at intervention and pre-existing advanced preoperative osteoarthritis. Moreover, reported complications ranged between 0% and 28.3 %.Interpretation: The Chiari osteotomy has high reported survival rates and is capable of restoring radiographic hip parameters to healthy values. When carefully selected by young age, and a low osteoarthritis score, patients benefit from the Chiari osteotomy with satisfactory survival rates. The position of the Chiari osteotomy in relation to the periacetabular osteotomies should be further (re-)explored.

Osteoporosis is a condition of increased bone fragility associated with fractures. Apart from primary genetic osteoporotic conditions, secondary osteoporosis in children is being increasingly recognized. As a result, there is growing interest in its prevention and treatment. Important goals of care are to prevent fractures, increase bone mass and trabecular and cortical thickness, reshape vertebral fractures, prevent (or correct) skeletal deformities, and improve mobility, independence, and quality of life. Secondary pediatric osteoporosis is often of multifactorial origin since affected children frequently have more than one acquired factor that is detrimental to bone health. Typical conditions causing osteoporosis are leukemias, progressive muscle or neurological disorders, as well as chronic inflammatory conditions and their treatment. Management of children with osteoporosis involves a multidisciplinary team involving pediatric experts from different subspecialties. With regard to prevention and early intervention, it is important to provide optimal management of any underlying systemic conditions including avoidance, or dose-reduction, of osteotoxic medications. Basic supporting life-style measures, such as appropriate nutrition, including adequate calcium intake and vitamin D, and physical activity are recommended, where possible. When pediatric treatment criteria for osteoporosis are met, antiresorptive drugs constitute the first pharmacological line treatment. Conclusion: This clinical review focuses on the prevention, treatment, and follow-up of children with, or at risk of developing, osteoporosis and the transition from pediatric to adult care. What is Known: • Osteoporosis and associated fractures can cause significant morbidity and reduce the quality of life. • The developing skeleton has huge potential for recovery and reshaping, thus early detection of fractures, assessment of recovery potential, and treatment of children with osteoporosis can prevent future fractures, deformities, and scoliosis, improve function and mobility, and reduce pain. What is New: • Osteoporosis in children and adolescents requires a multidisciplinary approach with a thorough assessment of recovery potential, and indication for therapy should be personalized. • Although bisphosphonates still represent the drug most commonly used to increase bone mass, improve mobility, and reduce pain and recurrence of fractures, new agents are being developed and could be beneficial in children with specific conditions.

Osteoporosis is a condition of increased bone fragility associated with fractures. Apart from primary genetic osteoporotic conditions, secondary osteoporosis in children is being increasingly recognized. As a result, there is growing interest in its prevention and treatment. Important goals of care are to prevent fractures, increase bone mass and trabecular and cortical thickness, reshape vertebral fractures, prevent (or correct) skeletal deformities, and improve mobility, independence, and quality of life. Secondary pediatric osteoporosis is often of multifactorial origin since affected children frequently have more than one acquired factor that is detrimental to bone health. Typical conditions causing osteoporosis are leukemias, progressive muscle or neurological disorders, as well as chronic inflammatory conditions and their treatment. Management of children with osteoporosis involves a multidisciplinary team involving pediatric experts from different subspecialties. With regard to prevention and early intervention, it is important to provide optimal management of any underlying systemic conditions including avoidance, or dose-reduction, of osteotoxic medications. Basic supporting life-style measures, such as appropriate nutrition, including adequate calcium intake and vitamin D, and physical activity are recommended, where possible. When pediatric treatment criteria for osteoporosis are met, antiresorptive drugs constitute the first pharmacological line treatment.This clinical review focuses on the prevention, treatment, and follow-up of children with, or at risk of developing, osteoporosis and the transition from pediatric to adult care.• Osteoporosis and associated fractures can cause significant morbidity and reduce the quality of life. • The developing skeleton has huge potential for recovery and reshaping, thus early detection of fractures, assessment of recovery potential, and treatment of children with osteoporosis can prevent future fractures, deformities, and scoliosis, improve function and mobility, and reduce pain.• Osteoporosis in children and adolescents requires a multidisciplinary approach with a thorough assessment of recovery potential, and indication for therapy should be personalized. • Although bisphosphonates still represent the drug most commonly used to increase bone mass, improve mobility, and reduce pain and recurrence of fractures, new agents are being developed and could be beneficial in children with specific conditions.

Background and purpose — Involvement of patient organizations is steadily increasing in guidelines for treatment of various diseases and conditions for better care from the patient’s viewpoint and better comparability of outcomes. For this reason, the Osteogenesis Imperfecta Federation Europe and the Care4BrittleBones Foundation convened an interdisciplinary task force of 3 members from patient organizations and 12 healthcare professionals from recognized centers for interdisciplinary care for children and adults with osteogenesis imperfecta (OI) to develop guidelines for a basic roadmap to surgery in OI. Methods — All information from 9 telephone conferences, expert consultations, and face-to-face meetings during the International Conference for Quality of Life for Osteogenesis Imperfecta 2019 was used by the task force to define themes and associated recommendations. Results — Consensus on recommendations was reached within 4 themes: the interdisciplinary approach, the surgical decision-making conversation, surgical technique guidelines for OI, and the feedback loop after surgery. Interpretation — The basic guidelines of this roadmap for the interdisciplinary approach to surgical care in children and adults with OI is expected to improve standardization of clinical practice and comparability of outcomes across treatment centers.

Aims The most important complication of treatment of developmental dysplasia of the hip (DDH) is avascular necrosis (AVN) of the femoral head, which can result in proximal femoral growth disturbances leading to pain, dysfunction, and eventually to early onset osteoarthritis. In this study, we aimed to identify morphological variants in hip joint development that are predictive of a poor outcome. Methods We retrospectively reviewed all patients who developed AVN after DDH treatment, either by closed and/or open reduction, at a single institution between 1984 and 2007 with a minimal follow-up of eight years. Standard pelvis radiographs obtained at ages one, two, three, five, and eight years, and at latest follow-up were retrieved. The Bucholz-Ogden classification was used to determine the type of AVN on all radiographs. Poor outcome was defined by Severin classification grade 3 or above on the latest follow-up radiographs and/or the need for secondary surgery. With statistical shape modelling, we identified the different shape variants of the hip at each age. Logistic regression analysis was used to associate the different modes or shape variants with poor outcome. Results In all, 135 patients with AVN were identified, with a minimum of eight years of follow-up. Mean age at time of surgery was 7.0 months (SD 0.45), and mean follow-up was 13.3 years (SD 3.7). Overall, 46% had AVN type 1 while 54% type 2 or higher. More than half of the patients (52.6%) had a poor outcome. We found 11 shape variants that were significantly associated with a poor outcome. These shape variants were predominantly linked to AVN type 2 or higher. Conclusion Specific morphological characteristics on pelvis radiographs of AVN hips were predictive for poor outcome, at a very young age. There was an overall stronger association to Bucholz-Ogden types 2-3-4 with the exception of two modes at age two and five years, linked to AVN type 1. Cite this article: Bone Joint J 2021;103-B(5):999–1004.

A solution for challenging hip dysplasia surgery could be a patient-specific 3D-printed shelf implant that is positioned extra-articular and restores the dysplastic acetabular rim to normal anatomical dimensions. The anatomical correction and biomechanical stability of this concept were tested in a canine model that, like humans, also suffers from hip dysplasia. Using 3D reconstructed computed tomography images the 3D shelf implant was designed to restore the radiological dysplastic hip parameters to healthy parameters. It was tested ex-vivo on three dog cadavers (six hips) with hip dysplasia. Each hip was subjected to a biomechanical subluxation test, first without and then with the 3D shelf implant in place. Subsequently, an implant failure test was performed to test the primary implant fixation. At baseline, the dysplastic hips had an average Norberg angle of 88±3° and acetabular coverage of 47±2% and subluxated at an average of 83±2° of femoral adduction. After adding the patient-specific shelf implants the dysplastic hips had an average Norberg angle of 122±2° and acetabular coverage of 67±3% and subluxated at an average of 117±2° of femoral adduction. Implant failure after primary implant fixation occurred at an average of 1330±320 Newton. This showed that the patient-specific shelf implants significantly improved the coverage and stability of dysplastic hips in a canine model with naturally occurring hip dysplasia. The 3D shelf is a promising concept for treating residual hip dysplasia with a straightforward technology-driven approach, however, the clinical safety needs to be further investigated in an experimental proof-of-concept animal study. This article is protected by copyright. All rights reserved.

Introduction: Lower limb malalignment is a major risk factor for knee osteoarthritis (OA) and is mainly diagnosed using the Hip Knee Ankle Angle (HKA). Therefore, accurate HKA measurements are indispensable. Objectives: This study aimed to research the effects of knee flexion, leg rotation, and X-ray beam height on the accuracy of the HKA measurement. To convert our findings into a guideline for obtaining whole leg radiographs (WLR) in favor of accuracy and reproducibility. Methods: An in vitro experiment was designed using sawbones (in 5° varus) of the whole lower limb, fixated in different leg rotation angles, knee flexion angles, and three different X-ray beam heights. Results: The HKA measurement error was 1° per 20° of leg rotation without flexion (P < .01). When 5° of flexion was added, the HKA measurement error was 0.8° per 20° rotation (P < .01). With 15° knee flexion, the HKA measurement error became 4° per 20° rotation (P < .01). Varying X-ray beam heights of 5cm (P = .959) and 10 cm (P = .967) did not cause any significant measurement errors. Conclusion: This study showed that leg rotation alone (without knee flexion) can lead to clinically relevant measurement errors when exceeding 9°. When there is 15° of knee flexion and 10° leg rotation the error becomes approximately 2°. Varying X-ray beam heights within a range of 10 cm does not affect the accuracy. Based on these findings, we propose guidelines for system setup and patient positioning during a WLR that is easy to apply and aims at minimizing errors when measuring the HKA.

Purpose The correlation between the degree of developmental hip dysplasia (DDH) measured on ultrasound images compared with that measured on radiographs is not clear. Most studies have compared ultrasonography (US) and radiographic images made at different times of follow-up. In this study the correlation between US images and radiographs of the hip made on the same day was evaluated. Methods US images and radiographs of both hips of 74 infants, who were treated for stable DDH, were reviewed in a retrospective study. Only infants who had an US examination and a radiograph on the same day were included. Results The correlation between α-angle of Graf and femoral head coverage on US was strong (p ≤ 0.0001). Weak correlations were found between the acetabular index of Tönnis on radiographs and α-angle of Graf on US (p = 0.049) and between acetabular index of Tönnis on radiographs and femoral head coverage of Morin on US (p = 0.100). Conclusion This study reports on the correlation between US and radiographic imaging outcomes, both made on the same day in patients for treatment and follow-up of DDH. Level of Evidence IV

Bone is a complex natural material with a complex hierarchical multiscale organization, crucial to perform its functions. Ultrastructural analysis of bone is crucial for our understanding of cell to cell communication, the healthy or pathological composition of bone tissue, and its three-dimensional (3D) organization. A variety of techniques has been used to analyze bone tissue. This article describes a combined approach of optical, scanning electron, and transmission electron microscopy for the ultrastructural analysis of bone from the nanoscale to the macroscale, as illustrated by two pathological bone tissues. By following a top-down approach to investigate the multiscale organization of pathological bones, quantitative estimates were made in terms of calcium content, nearest neighbor distances of osteocytes, canaliculi diameter, ordering, and D-spacing of the collagen fibrils, and the orientation of intrafibrillar minerals which enable us to observe the fine structural details. We identify and discuss a series of two-dimensional (2D) and 3D imaging techniques that can be used to characterize bone tissue. By doing so we demonstrate that, while 2D imaging techniques provide comparable information from pathological bone tissues, significantly different structural details are observed upon analyzing the pathological bone tissues in 3D. Finally, particular attention is paid to sample preparation for and quantitative processing of data from electron microscopic analysis.

Background The introduction of stem cell transplantation has improved life expectancy and cognitive outcome in patients with mucopolysaccharidosis I, but this condition remains associated with substantial residual disease in several parts of the body. Many patients have hip dysplasia with progressive medial flattening of the femoral head. Quantitative evidence on the effect of surgery on remodeling to sphericity of flattened femoral heads is lacking. In the present study, we used statistical shape modeling to quantify the effect of hip surgery on the sphericity of the femoral head in patients with mucopolysaccharidosis I. Methods We performed a retrospective case control study involving a series of 23 patients with hip dysplasia due to mucopolysaccharidosis I. Surgery was not offered to the first 11 children (control group). Following a change in treatment protocol, the next 12 children underwent bilateral proximal femoral varus derotation osteotomy and Pemberton osteotomy for the treatment of acetabular dysplasia with progressive femoral head flattening (surgery group). The surgery and control groups were compared with a reference group of patients with normal hips. Statistical shape modeling was used to quantify the shape of the femoral head (i.e., flattening and/or roundness of the epiphysis). Results The mean age at the time of stem cell transplantation in the surgery and control groups was comparable (1.2 years). The mean age at the time of surgical intervention was 5.5 years, and mean duration of postoperative follow-up was 3.3 years. Statistical shape modeling showed variations within the total group in terms of medial indentation, width, height, and sphericity of the femoral heads. In contrast to the progressive femoral head flattening in the control group, the surgery group showed improvement of the sphericity of the femoral head after surgery. The overall shape characteristics of the femoral head in the surgery group were similar to those of the reference group of patients with normal hips. Conclusions To our knowledge, this is the first study in patients with mucopolysaccharidosis I that has shown quantitative remodeling of the dysplastic, flattened femoral head to normal sphericity after increasing containment of the femoral head. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background Osteogenesis Imperfecta (OI) is a genetic disorder also known as ‘brittle bone disease’. The clinical manifestation of OI shows a wide variation. Therefore, care for patients with OI requires an interdisciplinary approach. The effectiveness of particular interventions and treatment protocols of interdisciplinary teams is not clear due to a non-standardized and wide variation of patient outcomes thus making the comparison of outcome measures available in the literature difficult. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of OI that comparisons across interdisciplinary treatment centers for OI will be possible in the future. Methods The Key4OI international interdisciplinary working group of 27 members used a consensus-driven modified Delphi approach to develop a set of global outcome measures for patients with OI. The International Classification of Functioning, Disability and Health (ICF), was used to define domains and organize the outcomes from the literature search. After reviewing the outcomes extracted from the literature, trials and registries, the working group agreed on a final selection of domains and their definition (ICF definition as well as a lay description). These domains were then presented to the focus groups who prioritized the outcome domains by taking into account the items important to the OI community. All content was collected and analyzed and final domains were determined. A consensus of appropriate measuring instruments for each domain was reached with Delphi rounds. The entire approach was in line with the International Consortium for Health Outcomes Measurement ICHOM methodology. Results More than 400 different outcome measures were identified in our literature search. After three Delphi rounds, 24 domains were selected. After the focus group sessions, the number of domains were reduced to 15. A consensus was reached on the measuring instruments to cover these domains for both children and adults. Conclusion The Key4OI project resulted in standard set of outcome measures focused on the needs and wishes of individuals with OI and their families. This outcome set will enable healthcare teams and systems to compare and to improve their care pathways and quality of care worldwide. Further studies are needed to evaluate the implementation of this standardized outcome set.

Background and purpose — Congenital pseudarthrosis of the tibia (CPT) is caused by local periosteal disease that can lead to bowing, fracturing, and pseudarthrosis. Current most successful treatment methods are segmental bone transport and vascularized and non-vascularized bone grafting. These methods are commonly hampered by discomfort, reoperations, and long-term complications. We report a combination of a vascularized fibula graft and large bone segment allograft, to improve patient comfort with similar outcomes. Patients and methods — 7 limbs that were operated on in 6 patients between November 2007 and July 2018 with resection of the CPT and reconstruction with a vascularized fibula graft in combination with a bone allograft were retrospectively studied. The mean follow-up time was 5.4 years (0.9–9.6). Postoperative endpoints: time to discharge, time to unrestricted weight bearing, complications within 30 days, consolidation, number of fractures, and secondary deformities. Results — The average time to unrestricted weight bearing with removable orthosis was 3.5 months (1.2–7.8). All proximal anastomoses consolidated within 10 months (2–10). 4 of the 7 grafts fractured at the distal anastomosis between 6 and 14 months postoperatively. After reoperation, consolidation of the distal anastomosis was seen after 2.8 months (2–4). 1 patient required a below-knee amputation. Interpretation — This case series showed favorable results of the treatment of CPT through a combination of a vascularized fibula graft and large bone segment allograft, avoiding the higher reintervention rate and discomfort with ring frame bone transport, and the prolonged non-weight bearing with vascularized fibula transfer without reinforcement with a massive large bone segment allograft.

Background and purpose ��� The shelf arthroplasty was the regular treatment for residual hip dysplasia before it was substituted by the peri-acetabular osteotomy. Yet, evidence regarding the survival of shelf arthroplasty surgery has never been systematically documented. Hence, we investigated the survival time of the shelf procedure until revision to THA in patients with primary hip dysplasia. Factors that influenced survival and complications were also examined, along with the accuracy of correcting radiographic parameters to characterize dysplasia. Material and methods ��� The inclusion criteria were studies of human adolescents and adults (> 16 years) with primary or congenital hip dysplasia who were treated with a shelf arthroplasty procedure. Data were extracted concerning patient characteristics, survival time, complications, operative techniques, and accuracy of correcting radiographic parameters. Results ��� Our inclusion criteria were applicable to 9 studies. The average postoperative Center-Edge Angle and Acetabular Head Index were mostly within target range, but large variations were common. Kaplan���Meier curves (endpoint: conversion to THA) varied between 37% at 20 years��� follow-up and 72% at 35 years��� follow-up. Clinical failures were commonly associated with pain and radiographic osteoarthritis. Only minor complications were reported with incidences between 17% and 32%. Interpretation ��� The shelf arthroplasty is capable of restoring normal radiographic hip parameters and is not associated with major complications. When carefully selected on minimal osteoarthritic changes, hip dysplasia patients with a closed triradiate cartilage may benefit from the shelf procedure with satisfactory survival rates. The importance of the shelf arthroplasty in relation to peri-acetabular osteotomies needs to be further (re)explored.

The 22q11.2 Deletion Syndrome (22q11.2DS) occurs in ~1:3,000–6,000 individuals. Features less typically associated with 22q11.2DS, such as orthopedic manifestations, may be overlooked or may not lead to appropriate diagnostic testing. Club foot has a general population prevalence of ~1:1,000 and has been occasionally described in association with 22q11.2DS. Our hypothesis is that the prevalence of club foot is higher in patients with 22q11.2DS. We performed a retrospective review in two specialized 22q11.2DS centers to determine the prevalence of club foot. “True club foot” requires treatment (either conservative or surgical), therefore we only included those patients with proof of treatment. We investigated whether congenital heart disease (CHD) and/or cleft palate were associated with the presence of club foot within 22q11.2DS. The records of 1,466 patients were reviewed. Of these, 48 (3.3%) had confirmation of club foot (95% Confidence Interval: 2.4–4.3): 22 (46%) had a bilateral, 12 (25%) left, and 14 (29%) right club foot. Within our study, neither a CHD and/or a cleft palate were associated with a club foot. The prevalence of club foot in 22q11.2DS is 30 times higher than that observed in the general population. This suggests the diagnosis of club foot, especially in the face of other typically associated abnormalities of 22q11.2DS, should provoke consideration of 22q11.2DS as an underlying diagnosis, particularly in the neonatal setting.

Purpose To collect and describe data on the natural history of abnormal ultrasound (US) findings in hips of infants under six months of age to serve as a reference to the design of screening programmes and treatment algorithms in the care for children with hip dysplasia. Methods A search in PubMed of the terms “DDH” and “ultrasound” was done to find hips with abnormal US findings that were not treated. In cases of multiple periods of follow-up, the classification of every period was evaluated separately (individual hip follow-up periods). Results Data of 13 561 hips with 16 991 follow-up periods were collected and analyzed. Most quantifiable classifications and follow-up periods were according to Graf (14 876) and a minor number of the hips had follow-up periods with femoral head coverage (FHC) (2115). Normal development without treatment in the first six months was for Graf 2a between 89% and 98%, for Graf 2c between 80% and 100% and for clustered data Graf 2a to 2c between 80% and 97%. For Graf 3 hips more than 50% were reported to develop into normal hips without treatment. As for Graf 4 hips this percentage was reported below 50%. For children with an FHC less than 50%, normalization was reported between 78% and 100%. Conclusion The natural history of developmental dysplasia of the hip (DDH) shows a benign course, especially in the well-centered hips. This outcome probably contributes to the fact that all studies on US screening of hips for detection of relevant DDH in order to improve outcomes of treatment are rated as substantially underpowered.

A mutation in GDF6 was recently found to underlie a multiple synostoses syndrome. In this report, we describe the second family with GDF6-related multiple synostoses syndrome (SYNS4), caused by a novel c.1287C>A/p.Ser429Arg mutation in GDF6. In addition to synostoses of carpal and/or tarsal bones, at least 6 of 10 affected patients in this family have been diagnosed with mild to moderate hearing loss. In four of them otosclerosis was said to be present, one patient had hearing loss due to severe stapes fixation at the age of 6 years, providing evidence that hearing loss in the GDF6-related multiple synostoses syndrome can be present in childhood. Two others had surgery for stapes fixation at adult age. We hypothesize that, identical to the recently published GDF6-related multiple synostoses family, the p.Ser429Arg mutation also leads to a gain of function. The previously reported c.1330T>A/pTyr444Asn mutation was located in a predicted Noggin and receptor I interacting domain and the gain of function was partly due to resistance of the mutant GDF6 to the BMP-inhibitor Noggin. The results in our family show that mutations predicting to affect the type II receptor interface can lead to a similar phenotype and that otosclerosis presenting in childhood can be part of the GDF6-related multiple synostoses syndrome.

— A delegation of 6 pediatric orthopedic surgeons from the Dutch Orthopedic Association (NOV) and 2 members of the board of the Dutch Parents’ Association for children with clubfoot created the guideline "The diagnosis and treatment of primary idiopathic clubfeet" between April 2011 and February 2014. The development of the guideline was supported by a professional methodologist from the Dutch Knowledge Institute of Medical Specialists. This evidence-based guideline process was new and unique, in the sense that the process was initiated by a parents’ association. This is the first official guideline in pediatric orthopedics in the Netherlands, and to our knowledge it is also the first evidence-based guideline on clubfoot worldwide. The guideline was developed in accordance with the criteria of the international AGREE instrument (AGREE II: Appraisal of Guidelines for Research and Evaluation II). The scientific literature was searched and systematically analyzed. In the second phase, conclusions and recommendations in the literature were formulated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Recommendations were developed considering the balance of benefits and harms, the type and quality of evidence, the values and preferences of the people involved, and the costs. The guideline is a solid foundation for standardization of clubfoot treatment in the Netherlands, with a clear recommendation of the Ponseti method as the optimal method of primary clubfoot treatment. We believe that the format used in the current guideline sets a unique example for guideline development in pediatric orthopedics that may be used worldwide. Our format ensured optimal collaboration between medical specialists and parents, and resulted in an important change in clubfoot care in the Netherlands, to the benefit of medical professionals as well as parents and patients. In this way, it is possible to improve professional collaboration between medical specialists and parents, resulting in an important change in clubfoot care in the Netherlands that will benefit medical professionals, parents, and patients. The guideline was published online, and is freely available from the Dutch Guideline Database (www.richtlijnendatabase.nl).

Background The effect of bracing over natural history of stable dysplastic hips is not well known. This multicenter randomized trial aimed at objectifying the effect of abduction treatment versus active surveillance in infants of 3 to 4 months of age. Methods Patients were randomized to either Pavlik harness or active surveillance group. Ultrasound was repeated at 6 and 12 weeks post randomization. The primary outcome was the degree of dysplasia using the Graf α-angle at 6 months of age. The measurement of the acetabular index (AI) on plain pelvis X-rays was used to identify persistent dysplasia after 9 months and walking age (after 18 months). Findings The Pavlik harness group (n = 55) and active surveillance group (n = 49) were comparable for predictors of outcome. At 12 weeks follow-up the mean α-angle was 60.5° ± 3.8° in the Pavlik harness group and 60.0° ± 5.6° in the active surveillance group. (p = 0.30). Analysis of secondary outcomes (standard of care) showed no treatment differences for acetabular index at age 10 months (p = 0.82) and walking age (p = 0.35). Interpretation Pavlik harness treatment of stable but sonographic dysplastic hips has no effect on acetabular development. Eighty percent of the patients will have a normal development of the hip after twelve weeks. Therefore, we recommend observation rather than treatment for stable dysplastic hips.

The majority of patients with osteogenesis imperfecta (OI) have mutations in the COL1A1 or COL1A2 gene, which has consequences for the composition of the bone matrix and bone architecture. The mutations result in overmodified collagen molecules, thinner collagen fibres and hypermineralization of bone tissue at a bone matrix level. Trabecular bone in OI is characterized by a lower trabecular number and connectivity as well as a lower trabecular thickness and volumetric bone mass. Cortical bone shows a decreased cortical thickness with less mechanical anisotropy and an increased pore percentage as a result of increased osteocyte lacunae and vascular porosity. Most OI patients have mutations at different locations in the COL1 gene. Disease severity in OI is probably partly determined by the nature of the primary collagen defect and its location with respect to the C-terminus of the collagen protein. The overall bone biomechanics result in a relatively weak and brittle structure. Since this is a result of all of the above-mentioned factors as well as their interactions, there is considerable variation between patients, and accurate prediction on bone strength in the individual patient with OI is difficult. Current treatment of OI focuses on adequate vitamin-D levels and interventions in the bone turnover cycle with bisphosphonates. Bisphosphonates increase bone mineral density, but the evidence on improvement of clinical status remains limited. Effects of newer drugs such as antibodies against RANKL and sclerostin are currently under investigation. This paper was written under the guidance of the Study Group Genetics and Metabolic Diseases of the European Paediatric Orthopaedic Society. Cite this article: Nijhuis WH, Eastwood DM, Allgrove J, Hvid I, Weinans HH, Bank RA, Sakkers RJ. Current concepts in osteogenesis imperfecta: bone structure, biomechanics and medical management.

Purpose: To assess the feasibility of deep learning-based high resolution synthetic CT generation from MRI scans of the lower arm for orthopedic applications. Methods: A conditional Generative Adversarial Network was trained to synthesize CT images from multi-echo MR images. A training set of MRI and CT scans of 9 ex vivo lower arms was acquired and the CT images were registered to the MRI images. Three-fold cross-validation was applied to generate independent results for the entire dataset. The synthetic CT images were quantitatively evaluated with the mean absolute error metric, and Dice similarity and surface to surface distance on cortical bone segmentations. Results: The mean absolute error was 63.5 HU on the overall tissue volume and 144.2 HU on the cortical bone. The mean Dice similarity of the cortical bone segmentations was 0.86. The average surface to surface distance between bone on real and synthetic CT was 0.48 mm. Qualitatively, the synthetic CT images corresponded well with the real CT scans and partially maintained high resolution structures in the trabecular bone. The bone segmentations on synthetic CT images showed some false positives on tendons, but the general shape of the bone was accurately reconstructed. Conclusions: This study demonstrates that high quality synthetic CT can be generated from MRI scans of the lower arm. The good correspondence of the bone segmentations demonstrates that synthetic CT could be competitive with real CT in applications that depend on such segmentations, such as planning of orthopedic surgery and 3D printing., Comment: This work has been accepted at the SPIE Medical Imaging 2019, Image Processing conference, paper 10949-54

Purpose Amputations and fitting surgery have a long history in children with limb deficiencies. With the current developments in limb reconstruction and new techniques in prosthetics, the indications for amputation and fitting surgery might have shifted, but still have a very important role in creating high functional performance, optimal participation and quality of life. The purpose of this current concepts article is to give an overview of the indications, dilemmas and technical considerations in the decision-making for amputation and fitting surgery. A special part of this overview is dedicated to the indications, variations and outcomes in rotationplasties. Methods The article is based on the experience of a multidisciplinary reconstruction team for children with complex limb deficiencies, as well as research of the literature on the various aspects that cover this multidisciplinary topic. Results For those children with a more severe limb deficiency, reconstruction is not always feasible for every patient. In those cases, amputation with prosthetic fitting can lead to a good result. Outcomes in quality of life and function do not significantly differ from the children that had reconstruction. For children with a postaxial deficiency with a femur that is too short for lengthening, and with a stable ankle and foot with good function, rotationplasty offers the best functional outcome. However, the decision-making between the different options will depend on different individual factors. Conclusions Amputations and rotationplasties combined with optimal prosthesis fitting in children with more severe limb deficiencies may lead to excellent short- and long-term results. An experienced multidisciplinary team for children with complex limb deficiencies should guide the patient and parents in the decision-making between the different options without or with prosthesis.

Background: Dysostosis multiplex contributes substantially to morbidity in patients with Hurler syndrome (mucopolysaccharidosis type I Hurler phenotype [MPS I-H]), even after successful hematopoietic stem cell transplantation (HSCT). One of the hallmarks of dysostosis multiplex in MPS I-H is hip dysplasia, which often requires surgical intervention. We sought to describe in detail the course of hip dysplasia in this group of patients, as assessed by radiographic analysis, and to identify potential outcome predictors. Methods: Longitudinal data were obtained from digitally scored pelvic radiographs of patients with MPS I-H using OrthoGon software for parameters including, but not limited to, the acetabular index, migration percentage, Smith ratio, and neck-shaft angle. Scoring was performed independently by two blinded observers. Additional information on genotype, enzyme replacement therapy pre-HSCT, donor chimerism, and enzyme activity post-HSCT were obtained. General trends and potential correlations were calculated with mixed-model statistics. Results: Fifty-two patients (192 radiographs) were included in this analysis. Intraobserver and interobserver variation analysis showed an intraclass correlation coefficient ranging from 0.78 to 1.00. Among the twenty-one patients with follow-up beyond the age of five years, the acetabular index was in the range of severe hip dysplasia in up to 86% of the patients. Severe coxa valga was seen in 91% of the patients. Lateral and superior femoral displacement were highly prevalent, with the migration percentage outside the reference range in up to 96% of the patients. Finally, anterior pelvic tilt increased with age (p = 0.001). No correlations were identified between clinical parameters and radiographic findings. Conclusions: Our study shows that progressive acetabular dysplasia as well as coxa valga and hip displacement are highly prevalent and progressive over time in patients with MPS I-H, despite successful HSCT. These data may provide essential natural history determinations for the assessment of efficacy of new therapeutic strategies aimed at improving skeletal outcomes in patients with MPS I-H. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Aims Open reduction is required following failed conservative treatment of developmental dysplasia of the hip (DDH). The Ludloff medial approach is commonly used, but poor results have been reported, with rates of the development of avascular necrosis (AVN) varying between 8% and 54%. This retrospective cohort study evaluates the long-term radiographic and clinical outcome of dislocated hips treated using this approach. Patients and Methods Children with a dislocated hip, younger than one year of age at the time of surgery, who were treated using a medial approach were eligible for the study. Radiographs were evaluated for the degree of dislocation and the presence of an ossific nucleus preoperatively, and for the degree of AVN and residual dysplasia at one and five years and at a mean of 12.7 years (4.6 to 20.8) postoperatively. Radiographic outcome was assessed using the Severin classification, after five years of age. Further surgical procedures were recorded. Functional outcome was assessed using the Pediatric Outcomes Data Collection Instrument (PODCI) or the Hip Disability and Osteoarthritis Outcome Score (HOOS), depending on the patient’s age. Results A total of 52 children (58 hips) were included. At the latest follow-up, 11 hips (19%) showed signs of AVN. Further surgery was undertaken in 13 hips (22%). A total of 13 hips had a poor radiological outcome with Severin type III or higher. Of these, the age at the time of surgery was significantly higher (p Conclusion This retrospective long-term follow-up study shows that one in five children with DDH who undergo open reduction using a medial surgical approach has poor clinical and/or radiological outcome. The poor outcome is not related to the presence of AVN (19%), but due to residual dysplasia. Cite this article: Bone Joint J 2018;100-B:822–7.

Background/Aims: To systematically assess contemporary knowledge regarding the effectiveness and safety of bisphosphonates (BPs) in children with osteogenesis imperfecta (OI). Methods: PubMed/MEDLINE, Embase, and Cochrane were searched for eligible articles up to June 2014. Studies eligible for inclusion were (randomized) controlled trials assessing the effects of BPs in children with OI. Methodological quality was assessed independently by 4 reviewers using the Cochrane Collaboration's tool for risk of bias. Results: Ten studies (519 children) were included. Four studies (40%) showed a low risk of bias. All studies investigating lumbar spine areal bone mineral density indicated a significant increase as a result of BP treatment. Most studies observed a significant decrease in fracture incidence. The most frequently reported adverse events were gastrointestinal complaints, fever, and muscle soreness. A significant decrease in (bone) pain due to BP treatment was observed in more than half of the studies. Most studies measuring urinary markers of bone resorption reported a significant decrease. The majority of studies with intravenous treatment showed a significant increase in lumbar projection area, whereas studies with oral treatment did not. Conclusions: Treatment with oral or intravenous BPs in children with OI results in an increase in bone mineral density and seems to be safe and well tolerated.

Background and purpose — Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue caused by a defect in collagen type I synthesis. For bone, this includes fragility, low bone mass, and progressive skeletal deformities, which can result in various degrees of short stature. The purpose of this study was to investigate development of bone mineral density in children with OI. Patients and methods — Development of lumbar bone mineral density was studied retrospectively in a cohort of 74 children with OI. Mean age was 16.3 years (SD 4.3). In 52 children, repeated measurements were available. Mean age at the start of measurement was 8.8 years (SD 4.1), and mean follow-up was 9 years (SD 2.7). A longitudinal data analysis was performed. In the total cohort (74 children), a cross-sectional analysis was performed with the latest-measured BMD. Age at the latest BMD measurement was almost equal for girls and boys: 17.4 and 17.7 years respectively. Result — Mean annual increase in BMD in the 52 childr...

Ultrasound screening for developmental dysplasia of the hip (DDH) is an innovation in preventive child health care in the Netherlands. Parental participation in the screening will be essential for the success of implementation of the screening. The aim of the current study was to investigate whether psychosocial factors (attitude, subjective norm, self-efficacy, perceived susceptibility, perceived severity, perceived effectiveness) predicted parental participation in the screening. A cross-sectional survey was conducted. Using a questionnaire, several background variables (organization, sociodemographic variables, and knowledge) and psychosocial variables were collected. Blockwise logistic regression was used to analyze the relations. A total of 703 questionnaires of participating parents (response 61.7%) and 393 questionnaires of nonparticipating parents were received (response 37.2%). When controlling for the background variables, attitude, subjective norm, self-efficacy, perceived susceptibility, and perceived effectiveness predicted parental participation in the screening (p< .05). Perceived severity of the dysplasia did not predict participation (p >.05). Psychosocial determinants influenced parental participation in the ultrasound screening for DDH. Emphasizing the positive aspects of the screening, highlighting the effectiveness, removing practical barriers, and being conscious of the influential role of child health care professionals on decision making are areas to focus on when organizing the ultrasound screening for DDH. Health care policy decision makers and child health care professionals should consider these determinants in order to stimulate parental participation

Purpose The aim of this cross-sectional cohort study is to describe the incidence of joint laxity and the correlation between joint laxity and radiological migration of the hip in children with Down syndrome. Methods Sixty-five children (2–19 years) with Down's syndrome were examined for joint laxity. For each subject, laxity scores for joints were carried out with the Bulbena method. Plane pelvic radiographs were used to determine the migration of the hip, according to Reimer's migration index. Results In this study, 26 out of 65 children with Down's syndrome (40 %) were diagnosed with general joint laxity. On the radiographs of the hips we found a mean Reimer's Migration Index of 5.2 % for all the subjects. Children with general joint laxity showed a lower Reimer's Migration Index (2.1 %). No significant correlation was found between general joint laxity and migration of the hip. Conclusions This study showed no relationship between joint laxity and migration of the hip in children with Down's syndrome. This implicates that we were not able to prove that joint laxity is the major factor in developing hip migration in children with Down's syndrome.

Introduction Bisphosphonates are currently the medical treatment most often used in children with osteogenesis imperfecta (OI). The purpose of this retrospective pre–post study was to evaluate the efficacy of treatment with bisphosphonates. We measured the effect by evaluating the number of outpatient department consultations and operative interventions before and after treatment with bisphosphonates in children with OI. Methods and materials Outpatient department consultation and operative intervention frequencies before and after treatment with bisphosphonates were registered. Children who had at least 2 years of medical records before treatment and at least 2 years after treatment were used in this study. Results Of 118 children who were treated with bisphosphonates, 51 (23 boys and 28 girls) fulfilled the inclusion criteria. Statistical analysis revealed a significant decrease in outpatient department consultations ( P < 0.000) and operative intervention ( P < 0.003) before and after bisphosphonate treatment. Conclusion The pre-post design of our study shows a significant reduction of the number of outpatient department consultations and operative interventions in patients with OI after treatment with bisphosphonates.

Doel: Rechtstreeks verwijzen door de jeugdarts naar de tweede lijn lijkt zinvol bij verdenking op heupdysplasie. Screening op heupdysplasie vindt plaats door lichamelijk onderzoek en de identificatie van risicofactoren. Echografische screening blijkt medisch en economisch gezien te leiden tot betere uitkomsten. Als onderdeel van een studie naar de haalbaarheid van implementatie van echografische screening in Nederland is onderzocht hoe ouders het verwijstraject beoordelen afhankelijk van de manier waarop zij naar de orthopaedisch chirurg zijn verwezen - rechtstreeks of via de huisarts - bij verdenking op heupdysplasie. Methode: Een vragenlijst is ontwikkeld om de ervaring van ouders die verwezen zijn te meten. In totaal is de vragenlijst gestuurd naar 355 ouders van kinderen die verwezen zijn tussen januari 2008 en november 2008. Resultaten: De respons op de vragenlijst was 46,5%. Ouders waren meer tevreden wanneer zij door de jeugdarts rechtstreeks waren verwezen dan wanneer dat via de huisarts plaatsvond. De tijd tussen de verwijzing en de eerste afspraak bij de orthopaedisch chirurg was korter als kinderen rechtstreeks werden verwezen. Tot slot waren ouders meer tevreden als zij het verwijstraject als niet stressvol ervoeren en als het traject soepel verliep. Conclusie: Gebaseerd op de perceptie van ouders, geeft dit onderzoek een eerste indicatie dat, met inachtneming van een aantal belangrijke randvoorwaarden, rechtstreeks verwijzen in het geval van heupdysplasie wenselijk is.

Background Transinguinal sonography can be used to demonstrate the position of the femoral head after reduction of a dislocated hip. Objective To determine whether transinguinal sonography can replace radiography and CT in the follow-up after reduction of a hip dislocation? Materials and methods Thirty-three children with 39 dislocated hips were followed up with sonography after reduction and immobilization in a spica cast. In cases of an abnormal position a CT scan was advised. A pelvic radiograph at the end of treatment served as an indicator that no dislocations were missed during the previous sonographic examinations. Results The repositioned hips were examined on 138 occasions. Twenty-four examinations were abnormal and CT scanning was performed on 11 occasions. In four children additional CT was done because a recurrent dislocation was suspected or because sonography was difficult to perform. No dislocations were demonstrated. In five children a recurrent dislocation was suspected, on one or more occasions. In all but one child a CT scan was performed that confirmed the dislocation. Conclusion Transinguinal sonography is well-suited to demonstrate a normal position of the femoral head in a spica cast. Transinguinal sonography decreases the number of radiographs and CT scans and reduces the exposure to ionizing radiation.

Purpose The evaluation of a construction that allows the exchange of circular and unilateral external fixators on the same fixation pins to the bone in outpatient circumstances during bone lengthening and alignment procedures. Methods Nine children were treated with this concept. After bone lengthening and alignment, the circular fixators were exchanged for unilateral fixators in the outpatient clinic to hold the position of the bony parts during the consolidation phase. Results The decrease of time needed to use the circular fixator during the treatment was considered to be an improvement in comfort. Conclusions The concept of using both a circular and a unilateral external fixator in a construction that allows the exchange of the external fixators in outpatient circumstances combines the advantages of both systems, and creates more options in the different stages of bone deformity correction. Patient comfort is increased by the decrease of time needed to use the circular fixator.

Background: It is increasingly recognized that healthcare is a complex system with limited resources and many interacting sources of both positive and negative feedback. Discrete-event simulation (DES) is a tool that readily accommodates questions of capacity planning, throughput management and interacting resources. As a result the use of DES in informing healthcare decision making is increasing. However, understanding when and how to build a DES model and use it for policy making is not yet a common knowledge.Methods: The steps in building a DES model will be demonstrated using a real-world example, i.e., pediatric ultrasound screening for hip dysplasia. The main components of a DES model such as entities, resources and queues will be introduced and we will examine questions such as referral schedule, number of ultrasound machines and type of screeners and how these entities interact. Finally a review of the statistical techniques appropriate to DES will be provided.Conclusion: Discrete-event simulation is a valuable tool in the policymakers armentarium. It can be used effectively to analyze and understand complex healthcare systems and policy problems such as population screening. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Objective To study in children with achondroplasia the response to exercise and muscle strength compared with healthy peers and to describe the relation between exercise capacity, anthropometric factors, and physical activity. Study design Patients (7 boys and 10 girls; mean age, 11.8 ± 3.3 years) with achondroplasia performed a maximal treadmill exercise test. Anthropometric variables and muscle strength were measured and compared with the general population. The level of everyday physical activity was measured by using a diary. Functional ability was measured by using the Activity Scale for Kids. Results The exercise capacity of the children with achondroplasia was significantly reduced compared with reference values. All anthropometrical measurements differed significantly from reference values. There was a decrease in muscle strength in almost all muscle groups. We found a reduced physical activity level and impairments in functional ability. Conclusions Cardiopulmonary exercise capacity and muscle strength in children with achondroplasia was reduced compared with reference values. Children with achondroplasia have a unique response to exercise. Clinicians should take these characteristic differences into account when the exercise capacity of subjects with achondroplasia is being tested.

Objective. To describe the clinical features, osseal characteristics, and collagen biochemistry in children who attended our clinic with predominantly generalized hypomobility of the joints, in combination with musculoskeletal complaints or abnormal walking, and no known syndrome or known rheumatic, neurologic, skeletal, metabolic, or connective tissue disorder was present. Methods. Nineteen children who attended the Children’s Hospital of the University Medical Center Utrecht for generalized hypomobility of the joints (mean age: 11.6; standard deviation: 2.7), in combination with musculoskeletal complaints or abnormal walking as primary complaints (symptomatic generalized hypomobility [SGH]), were compared with an age-matched reference group of 284 healthy children with normal mobility of the joints. Anthropometrics, range of joint motion, muscle strength, exercise tolerance, motor development, quantitative ultrasound measurements of bone, and degradation products of collagen in urine were studied. Collagen modifications were determined in skin biopsies of 3 children and in hypertrophic scar tissue of another child, all with SGH. Results. The range of joint motion was significantly decreased in almost all joints of all 19 children and after adjustment for age, gender, body weight, and height, significantly lower than that of the reference group (−108.3 degrees; 95% confidence interval [CI]: −136.9 to −79.8). Quantitative ultrasound measurements as well as urinary pyridinoline cross-link levels were, after adjustment for possible confounders, significantly lower in SGH children (broad-band ultrasound attenuation: −9.6 dB/MHz [95% CI: −17.4 to −1.9]; speed of sound: −25.0 m/s [95% CI: −39.7 to −10.3]; hydroxylysylpyridinoline: −50.1 μmol/mmol [95% CI: −87.6 to −12.6], lysylpyridinoline: −21.3 μmol/mmol [95% CI: −34.0 to −8.6]). An increased amount of pyridinoline cross-links per collagen molecule was observed in skin and hypertrophic scar tissue, in combination with increased amounts of collagen. Conclusion. SGH in children is considered a new clinical entity with specific clinical characteristics and might be related to an increased stiffness of connective tissue as a result of higher amounts of collagen with increased cross-linking.

Summary Background Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial. Methods 34 children recruited from the Dutch national centre for osteogenesis imperfecta were randomly assigned olpadronate (10 mg/m 2 daily; n=16) or placebo (n=18) for 2 years. All children also received calcium and vitamin D supplements. Primary endpoints were incident fractures of long bones and changes in bone mineral content (BMC), bone mineral density (BMD), and functional outcome. Anthropometry, vertebral height, and urinary markers of bone resorption were also studied. Analyses were by intention to treat. Findings Fracture follow-up was complete for all the children, including two who withdrew from the study (one from each group). Olpadronate treatment was associated with a 31% reduction in relative risk of fracture of long bones (hazard ratio 0·69 [95% CI 0·52–0·91], p=0·01). The olpadronate group showed significantly greater increases than the placebo group in spinal BMC (difference between groups 2·24 g/year [0·20–4·29], p=0·03) and spinal BMD (difference between groups 0·054 g/cm 2 per year [0·012–0·096], p=0·01). There were no detectable effects on functional outcome, anthropometrics, or vertebral height and no differences between the groups in changes in urinary markers of bone resorption. Interpretation Oral treatment with olpadronate at a daily dose of 10 mg/m 2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta. However, the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved, and further studies are needed.

Objectives. Children with generalized hypermobility of the joints and musculoskeletal complaints frequently visit pediatric clinics, but many show no currently known collagen or other possibly related diseases. Whether the symptoms are confined to the musculoskeletal system is unknown. We assessed whether such children have detectable differences in laxity of connective tissue present in organ systems other than joints. We also assessed whether children with generalized joint hypermobility and musculoskeletal complaints have more profound systemic changes in connective tissue of various organ systems as compared with children with generalized joint hypermobility without musculoskeletal complaints. Methods. Anthropometrics, range of joint motion, muscle strength, skin extensibility, blood pressure, quantitative ultrasound measurements of bone, and degradation products of collagen were studied in 15 prepubertal children with generalized joint hypermobility and musculoskeletal complaints and compared with a population-based reference group of 95 nonsymptomatic prepubertal children. Symptomatic hypermobile children were also compared with children of the population-based reference group who had asymptomatic hypermobility of the joints ( n = 16). Results. Children with symptomatic generalized joint hypermobility had significantly higher skin extensibility (5.6 mm/15 kPa, 95% confidence interval [CI]: 4.0–7.1), lower quantitative ultrasound measurements (speed of sound: −26.8 m/s; 95% CI: −41.1 to −12.6) in bone, and lower systolic and diastolic blood pressure (−8.0 mmHg, 95% CI: −13.3 to −2.8; and −6.0 mmHg, 95% CI: −10.0 to −2.2, respectively) as compared with the total reference group. Also, they had significantly lower excretion of urinary hydroxylysylpyridinoline cross-links (mean difference: −51.3 μmol/mmol; 95% CI: −92.2 to −10.4) as well as lysylpyridinoline cross-links (−18.7 μmol/mmol; 95% CI: −36.9 to −0.5). Age, gender, body weight, height, and particularly cross-links excretion did not explain group differences in clinical and bone characteristics. After adjustment for age, gender, body weight, and height, children with symptomatic generalized joint hypermobility ( n = 15) had significantly higher total range of joint motion (117.8 degrees; 95% CI: 77.7–158.0), skin extensibility (3.5 mm/15 kPa; 95% CI: 1.6–5.3), lower quantitative ultrasound measurements in bone (speed of sound: −27.9 m/s; 95% CI: −48.4 to −7.5), borderline lower diastolic blood pressure (−4.9 mmHg; 95% CI: −10.7–0.9), and significantly higher degradation products in urine (hydroxyproline/creatinine: 21.2 μmol/mmol; 95% CI: 2.3–40.1) as compared with asymptomatic hypermobile children of the total reference group ( n = 16). After adjustment for possible confounders, children with generalized joint hypermobility without musculoskeletal complaints had a significantly higher total range of joint motion and more profound skin extensibility, as compared with the reference group ( n = 79). Conclusions. Clinically manifested symptoms in otherwise healthy children with generalized joint hypermobility are accompanied by increases in the laxity of other body tissues. Thus, generalized joint hypermobility with musculoskeletal symptoms does not seem to be restricted to joint tissues. In symptomatic hypermobile children, a more systemic derangement was also present as compared with asymptomatic hypermobile children.