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Hypochondroplasia (HCH) is a rare skeletal dysplasia causing mild short stature. There is a paucity of growth reference charts for this population. Anthropometric data were collected to generate height, weight, and head circumference (HC) growth reference charts for children with a diagnosis of HCH. Mixed longitudinal anthropometric data and genetic analysis results were collected from 14 European specialized skeletal dysplasia centers. Growth charts were generated using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were collected from 188 (79 female) children with a diagnosis of HCH aged 0-18 years. Of the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). The data were used to generate growth references for height, weight, and HC, plotted as charts with seven centiles from 2nd to 98th, for ages 0-4 and 0-16 years. HCH-specific growth charts are important in the clinical care of these children. They help to identify if other comorbidities are present that affect growth and development and serve as an important benchmark for any prospective interventional research studies and trials.
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Osso e Ossos/anormalidades , Nanismo , Deformidades Congênitas dos Membros , Lordose , Osteocondrodisplasias , Criança , Humanos , Feminino , Gráficos de Crescimento , Estudos Prospectivos , Estatura/genética , Nanismo/diagnóstico , Nanismo/genética , Valores de ReferênciaRESUMO
Achondroplasia is associated with foramen magnum stenosis. We report a male infant with achondroplasia and centrally mediated obstructive apnoea who underwent two foramen magnum decompression due to bone regrowth. He presented at six weeks of age with breath holding and apnoeic episodes associated with significant desaturation, requiring non-invasive ventilation. Craniospinal imaging revealed a narrow foramen magnum without signal change in the spinal cord. Sleep studies showed obstructive, but not central, apnoea. Respiratory abnormalities persisted and reimaging at two months showed development of significant signal changes at the cervicomedullary junction (CMJ). He underwent emergency foramen magnum decompression with initial clinical improvement. Ten days later he relapsed with further apnoeic episodes requiring respiratory support. After extensive re-investigations including CT and MRI, incomplete initial decompression and foramen magnum restenosis were considered and confirmed with a CT head scan 15 weeks after the initial operation. Repeat decompression of bone and removal of thickened dural bands resulted in complete resolution of the apnoeic episodes. Obstructive sleep apnoea can be centrally mediated and further decompression of foramen magnum stenosis should be considered, especially if significant respiratory compromise persists or recurs.
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Acondroplasia , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Humanos , Lactente , Masculino , Forame Magno/diagnóstico por imagem , Forame Magno/cirurgia , Constrição Patológica/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/complicações , Descompressão Cirúrgica/métodos , Acondroplasia/complicações , Acondroplasia/cirurgiaRESUMO
Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH presents in toddlers or school-age children, as limb-to-trunk disproportion and is often mild and easily overlooked during infancy. We report experiences from a single-center UK HCH-cohort of 31 patients, the rate of antenatal HCH detection in our cohort (13/31, 41.9%) and describe relevant case-data for this subset of 13 patients. Inclusion criteria were patients with confirmed molecular HCH diagnosis (by age 3 years) and presenting with short long-bones or large head size on antenatal ultrasound scan. We then conducted a systematic literature review using PUBMED and MEDLINE, analyzing patients with HCH and related antenatal findings. Antenatally suspected (with subsequent molecular confirmation) HCH has been reported 15 times in the literature (2004-2019). Key markers (consistent in both groups) included reduced; femur length, humeral length and increased; biparietal diameter and head circumference. HCH is increasingly detected both antenatally and in infancy, contrary to previous descriptions. This is likely due to greater HCH awareness, improved imaging, and easier molecular testing. Thus, one should consider HCH outside the classical presenting period. Studying the natural history of younger patients with HCH is important with the advent of several targeted FGFR3 therapies currently in trials for Achondroplasia, that may soon be trialed in HCH.
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Acondroplasia/diagnóstico , Osso e Ossos/anormalidades , Nanismo/diagnóstico , Diagnóstico Precoce , Deformidades Congênitas dos Membros/diagnóstico , Lordose/diagnóstico , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Acondroplasia/genética , Acondroplasia/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Nanismo/diagnóstico por imagem , Nanismo/genética , Nanismo/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Humanos , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Lordose/diagnóstico por imagem , Lordose/genética , Lordose/patologia , Mutação/genética , Gravidez , Reino UnidoRESUMO
A pre-meeting workshop on Long Bone Pathology in Children with Achondroplasia was held in Salzburg, Austria at the 11th International Conference on Children's Bone Health (ICCBH) 22-25 June 2024. There remains poor understanding and awareness amongst physicians managing achondroplasia of the underlying pathophysiology, radiology, natural history and orthopaedic procedures available for long bone deformities and restrictions. The structure of the workshop consisted of presentation of the results of a multinational patient survey on views of leg lengthening in achondroplasia, lectures, a debate and an interactive round table discussion. In total 150 attendees from 71 different cities and 31 countries were in attendance.
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A pre-meeting workshop on spinal complications in children and adults with achondroplasia was held in Dublin, Ireland at the 10th International Conference on Children's Bone Health (ICCBH) 2-5 July 2022. The pathophysiology, natural history and medical/surgical management of thoraco-lumbar kyphosis and spinal stenosis remains poorly described in the literature. The structure of the workshop consisted of lectures, a debate and an interactive round table discussion. In total over 100 delegates affiliated to over 70 institutions from 20 countries were in attendance.
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Acondroplasia , Cifose , Estenose Espinal , Adulto , Criança , Humanos , Acondroplasia/complicações , Irlanda , Cifose/complicações , Estenose Espinal/complicações , Estenose Espinal/cirurgia , Coluna VertebralRESUMO
Achondroplasia, the most common skeletal dysplasia, is characterized by a variety of medical, functional and psychosocial challenges across the lifespan. The condition is caused by a common, recurring, gain-of-function mutation in FGFR3, the gene that encodes fibroblast growth factor receptor 3. This mutation leads to impaired endochondral ossification of the human skeleton. The clinical and radiographic hallmarks of achondroplasia make accurate diagnosis possible in most patients. However, marked variability exists in the clinical care pathways and protocols practised by clinicians who manage children and adults with this condition. A group of 55 international experts from 16 countries and 5 continents have developed consensus statements and recommendations that aim to capture the key challenges and optimal management of achondroplasia across each major life stage and sub-specialty area, using a modified Delphi process. The primary purpose of this first International Consensus Statement is to facilitate the improvement and standardization of care for children and adults with achondroplasia worldwide in order to optimize their clinical outcomes and quality of life.
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Acondroplasia , Qualidade de Vida , Acondroplasia/diagnóstico , Acondroplasia/genética , Acondroplasia/terapia , Consenso , Humanos , Mutação , Osteogênese , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
OBJECTIVES: Nutritional rickets may be a preventable cause of craniosynostosis. This potential association is under-recognised. A late diagnosis of craniosynostosis may result in reduced brain growth, raised intracranial pressure and long-term psychosocial problems. CASE PRESENTATION: We present four cases of craniosynostosis associated with nutritional rickets. Those who had delayed presentation underwent emergency craniotomy. CONCLUSIONS: Treatment of nutritional rickets and early identification of craniosynostosis can reduce morbidity in these children.
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Craniossinostoses/patologia , Raquitismo Hipofosfatêmico Familiar/complicações , Pré-Escolar , Craniossinostoses/etiologia , Feminino , Humanos , Lactente , Masculino , PrognósticoRESUMO
We report a further case of spondylometaphyseal dysplasia - corner fracture type due to the fibronectin-1 gene (SMD-FN1) in a child originally thought to have metaphyseal chondrodysplasia-Brussels type (MCD Brussels). We highlight phenotypic differences with the SMD-FN1 published reports. This case is unique in terms of the method of molecular confirmation. Findings from the 100 000 Genomes Project were originally negative (in both tier 1 and 2); however, subsequent reanalysis, initiated by an automated search for new gene-disease associations in PanelApp, highlighted a candidate diagnostic variant. Our child had short stature, facial dysmorphism, spondylometaphyseal dysplasia and corner fractures and a heterozygous de novo missense variant in FN1 (c.675C>G p.(Cys225Trp), which was likely pathogenic. The variant matched the clinical and radiological features and a diagnosis of SMD-FN1 was confirmed. We explore the diagnostic journey of this patient, compare her findings with the previous 15 patients reported with SMD-FN1 and discuss the diagnostic utility of automated reanalysis. We consider differences and similarities between MCD Brussels and SMD-FN1, by reviewing literature on both conditions and assess whether they are in fact the same disorder.
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Transtornos do Crescimento/diagnóstico , Articulação do Quadril/anormalidades , Osteocondrodisplasias/diagnóstico , Fraturas da Tíbia/diagnóstico , Criança , Feminino , Fibronectinas/genética , Transtornos do Crescimento/genética , Heterozigoto , Humanos , Mutação de Sentido Incorreto/genética , Osteocondrodisplasias/genética , Fenótipo , Fraturas da Tíbia/genéticaRESUMO
BACKGROUND: Achondroplasia is associated with foramen magnum stenosis (FMS) and significant risk of morbidity and sudden death in infants. A sensitive and reliable method of detecting infants who require decompressive surgery is required. This study aims to describe the incidence and severity of FMS in an unselected, sequential series of infants using a novel MRI score and retrospectively correlate severity with clinical examination and cardiorespiratory sleep (CRS) studies. METHODS: The Achondroplasia Foramen Magnum Score (AFMS) was developed and scores were retrospectively correlated with clinical and CRS data over a 3-year period. RESULTS: Of 36 infants (M:F, 18:18), 2 (5.6%) did not have FMS (AFMS0); 13 (36.1%) had FMS with preservation of the cerebrospinal fluid (CSF) spaces (AFMS1); 3 (8.3%) had FMS with loss of the CSF space but no spinal cord distortion (AFMS2); 13 (36.1%) had FMS with flattening of the cervical cord without signal change (AFMS3); and 5 (13.9%) had FMS resulting in cervical cord signal change (AFMS4). Mean Total Apnea and Hypopnea Index (TAHI) for AFMS0-4 was 3.4, 6.41, 2.97, 10.5 and 25.8, respectively. Severe TAHI had a specificity of 89% but only a 59% sensitivity for AFMS3-4. Neurological examination was normal in 34/36 (94%) patients. Overall, 9/36 (25%) infants required neurosurgery with minimal surgical complications. CONCLUSIONS: Clinical examination and CRS have a low sensitivity for predicting the effects of foramen stenosis on the spinal cord. Routine screening with MRI using AFMS can aid in detecting early spinal cord changes and has the potential to reduce infant morbidity and mortality.
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Acondroplasia/diagnóstico , Constrição Patológica/diagnóstico , Forame Magno/patologia , Índice de Gravidade de Doença , Acondroplasia/diagnóstico por imagem , Acondroplasia/cirurgia , Algoritmos , Pré-Escolar , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/cirurgia , Árvores de Decisões , Descompressão Cirúrgica , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Triagem Neonatal , Valor Preditivo dos TestesRESUMO
BACKGROUND: Skeletal dysplasia (SD) conditions are rare genetic diseases of the skeleton, encompassing a heterogeneous group of over 400 disorders, and represent approximately 5% of all congenital anomalies. Developments in genetic and treatment technologies are leading to unparalleled therapeutic advances; thus, it is more important than ever to molecularly confirm SD conditions. Data on 'rates-of-molecular yields' in SD conditions, through exome sequencing approaches, is limited. Figures of 39% and 52.5% have been reported in the USA (n = 54) and South Korea (n = 185) respectively. METHODS: We discuss a single-centre (in the UK) experience of whole-exome sequencing (WES) in a cohort of 15 paediatric patients (aged 5 months to 12 years) with SD disorders previously molecularly unconfirmed. Our cohort included patients with known clinical diagnoses and undiagnosed skeletal syndromes. Extensive phenotyping and expert radiological review by a panel of international SD radiology experts, coupled with a complex bioinformatics pipeline, allowed for both gene-targeted and gene-agnostic approaches. RESULTS: Significant variants leading to a likely or confirmed diagnosis were identified in 53.3% (n = 8/15) of patients; 46.7% (n = 7/15) having a definite molecular diagnosis and 6.7% (n = 1/15) having a likely molecular diagnosis. We discuss this in the context of a rare disease in general and specifically SD presentations. Of patients with known diagnoses pre-WES (n = 10), molecular confirmation occurred in 7/10 cases, as opposed to 1/5 where a diagnosis was unknown pre-test. Thus, diagnostic return is greatest where the diagnosis is known pre-test. For WGS (whole genome sequencing, the next iteration of WES), careful case selection (ideally of known diagnoses pre-test) will yield highest returns. CONCLUSIONS: Our results highlight the cost-effective use of WES-targeted bioinformatic analysis as a diagnostic tool for SD, particularly patients with presumed SD, where detailed phenotyping is essential. Thorough co-ordinated clinical evaluation between clinical, radiological, and molecular teams is essential for improved yield and clinical care. WES (and WGS) yields will increase with time, allowing faster diagnoses, avoiding needless investigations, ensuring individualised patient care and patient reassurance. Further diagnoses will lead to increased information on natural history/mechanistic details, and likely increased therapies and clinical trials.
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Sequenciamento do ExomaRESUMO
Achondroplasia, the most common form of disproportionate short stature, is caused by a variant in the fibroblast growth factor receptor 3 (FGFR3) gene. Advances in drug treatment for achondroplasia have underscored the need to better understand the natural history of this condition. This article provides a critical review and discussion of the natural history of achondroplasia based on current literature evidence and the perspectives of clinicians with extensive knowledge and practical experience in managing individuals with this diagnosis. This review draws evidence from recent and ongoing longitudinal natural history studies, supplemented with relevant cross-sectional studies where longitudinal research is lacking, to summarize the current knowledge on the nature, incidence, chronology, and interrelationships of achondroplasia-related comorbidities across the lifespan. When possible, data related to adults are presented separately from data specific to children and adolescents. Gaps in knowledge regarding clinical care are identified and areas for future research are recommended and discussed.
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Acondroplasia , Forame Magno , Acondroplasia/genética , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Estudos LongitudinaisRESUMO
The presence of a larger than usual number of Wormian bones (accessory skull bones completely surrounded by a suture line) is a well-known radiographic sign of osteogenesis imperfecta (OI), but the phenotypic and genotypic correlates are not well characterized. In the present study we retrospectively analyzed skull radiographs of 195 OI patients (median age 11.8 years, range 0.4-48 years; 100 female). A significant number of Wormian bones (SNWB, defined as the presence of 10 or more Wormian bones) were found in at least one patient in all of the OI types studied (I, III to VII). SNWB were observed in 35% of patients with OI type I, in 96% of patients with OI type III and 78% of patients with OI type IV. SNWB were present in 28% of patients with haploinsufficiency (nonsense and frameshift) mutations in COL1A1, in 96% of patients with helical glycine substitutions in the alpha 1 chain of collagen type I and in 72% of patients with helical glycine substitutions in the alpha 2 chain of collagen type I. Stepwise multivariate logistic regression analysis showed that height z-score, an indicator of disease severity, was inversely related with the prevalence of SNWB. SNWB were visible in 19 of the 26 patients who had skull radiographs in the first year of life, including a 2-week-old newborn. Thus, it appears that SNWB occur more frequently in more severely affected OI patients and seem to develop mostly in utero.
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Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Crânio/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Colágeno/genética , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Genótipo , Humanos , Lactente , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteogênese Imperfeita/diagnóstico por imagem , Radiografia , Crânio/diagnóstico por imagem , Adulto JovemRESUMO
Osteoporosis in children differs from adults in terms of definition, diagnosis, monitoring and treatment options. Primary osteoporosis comprises primarily of osteogenesis imperfecta (OI), but there are significant other causes of bone fragility in children that require treatment. Secondary osteoporosis can be a result of muscle disuse, iatrogenic causes, such as steroids, chronic inflammation, delayed or arrested puberty and thalassaemia major. Investigations involve bone biochemistry, dual-energy X-ray absorptiometry scan for bone densitometry and vertebral fracture assessment, radiographic assessment of the spine and, in some cases, quantitative computed tomography (QCT) or peripheral QCT. It is important that bone mineral density (BMD) results are adjusted based on age, gender and height, in order to reflect size corrections in children. Genetics are being used increasingly for the diagnosis and classification of various cases of primary osteoporosis. Bone turnover markers are used less frequently in children, but can be helpful in monitoring treatment and transiliac bone biopsy can assist in the diagnosis of atypical cases of osteoporosis. The management of children with osteoporosis requires a multidisciplinary team of health professionals with expertise in paediatric bone disease. The prevention and treatment of fragility fractures and improvement of the quality of life of patients are important aims of a specialised service. The drugs used most commonly in children are bisphosphonates, that, with timely treatment, can give good results in improving BMD and reshaping vertebral fractures. The data regarding their effect on reducing long bone fractures are equivocal. Denosumab is being used increasingly for various conditions with mixed results. There are more drugs trialled in adults, but these are not yet licenced for children. Increasing awareness of risk factors for paediatric osteoporosis, screening and referral to a specialist team for appropriate management can lead to early detection and treatment of asymptomatic fractures and prevention of further bone damage.
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X-linked hypophosphataemia (XLH) is caused by a pathogenic variant in the PHEX gene, which leads to elevated circulating FGF23. High FGF23 causes hypophosphataemia, reduced active vitamin D concentration and clinically manifests as rickets in children and osteomalacia in children and adults. Conventional therapy for XLH includes oral phosphate and active vitamin D analogues but does not specifically treat the underlying pathophysiology of elevated FGF23-induced hypophosphataemia. In addition, adherence to conventional therapy is limited by frequent daily dosing and side effects such as gastrointestinal symptoms, secondary hyperparathyroidism and nephrocalcinosis. Burosumab, a recombinant human IgG1 MAB that binds to and inhibits the activity of FGF23, is administered subcutaneously every 2 weeks. In clinical trials (phase 2 and 3) burosumab was shown to improve phosphate homeostasis that consequently resolves the skeletal/non-skeletal manifestations of XLH. Burosumab was licensed in Europe (February 2018) with the National Institute for Health and Care Excellence, UK approving use within its marketing authorisation in October 2018. In this publication, the British Paediatric and Adolescent Bone Group (BPABG) reviewed current evidence and provide expert recommendations for care pathway and management of XLH with burosumab.
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Cyclical intravenous treatment with pamidronate is widely used to treat osteogenesis imperfecta (OI) types I, III, and IV, which are due to dominant mutations affecting collagen type I alpha chains. There is no information about the effects of pamidronate in children with OI type VII, an autosomal-recessive form of OI caused by a mutation in the cartilage-associated protein gene. In this retrospective single-center study, we compared the effects of pamidronate in four girls with OI type VII (age range 3.9-12.7 years) to those in eight girls with OI types caused by collagen type I mutations who were matched for age and disease severity. During 3 years of pamidronate therapy, lumbar spine areal bone mineral density increased and lumbar vertebral bodies improved in shape in patients with OI type VII. Other outcomes such as fracture rates and mobility scores did not show statistically significant changes in this small study cohort. There were no significant side effects noted during the time of follow-up. Thus, intravenous treatment with pamidronate seems to be safe and of some benefit in patients with OI type VII.
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Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Ósseas/prevenção & controle , Osteogênese Imperfeita/tratamento farmacológico , Adolescente , Análise Química do Sangue , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Osso e Ossos/metabolismo , Criança , Pré-Escolar , Colágeno/genética , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Difosfonatos/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Mutação/genética , Osteogênese Imperfeita/sangue , Osteogênese Imperfeita/genética , Pamidronato , Estudos RetrospectivosRESUMO
A pre-meeting workshop on foramen magnum stenosis in children with achondroplasia was held in Salzburg, Austria at the 9th International Conference on Children's Bone Health (ICCBH) 22-25 June 2019. The screening, monitoring and surgical approach to foramen magnum stenosis still remains controversial with conflicting guidance in the literature. The structure of the workshop consisted of lectures, a debate, expert and delegate discussion and concluded with a research proposal and further next steps. In total, representation by 40 institutions from 22 different countries that care for approximately 1375 children with achondroplasia, were in attendance.
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Acondroplasia/patologia , Forame Magno/patologia , Acondroplasia/diagnóstico por imagem , Acondroplasia/fisiopatologia , Áustria , Forame Magno/diagnóstico por imagem , Forame Magno/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Programas de RastreamentoRESUMO
Osteonecrosis of the jaw (ONJ) has been described as a complication of bisphosphonate therapy in adults. In the present study, we did not find a case of ONJ among 278 pediatric patients who had received intravenous pamidronate during childhood or adolescence.
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Anti-Inflamatórios/farmacologia , Difosfonatos/uso terapêutico , Doenças Maxilomandibulares/terapia , Osteonecrose/terapia , Extração Dentária/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Infusões Intravenosas , Masculino , PamidronatoRESUMO
UNLABELLED: Hyperplastic callus formation was assessed in 23 patients with osteogenesis imperfecta type V. Hyperplastic callus mostly affected long bones in the lower extremities and occurred predominantly during phases of rapid growth. INTRODUCTION: Hyperplastic callus (HPC) formation is one of the most conspicuous features of osteogenesis imperfecta (OI) type V, but the natural history of HPC has not been well characterized. MATERIALS AND METHODS: In this retrospective single-center study, we assessed HPC in 23 OI type V patients (9 females and 14 males). RESULTS: Fifteen patients (65%) had HPC at 48 skeletal sites, 30 of which affected the lower limbs. The number of HPC sites per patient ranged from 0 to 7, with an average of 2.6 for men and 1.1 for women (p = 0.047 for this sex difference; t-test). New HPC formation was observed both after fractures and outside of the context of fractures. Only a minority of lower limb fractures (26%) precipitated HPC formation. After an initial enlargement phase, HPC lesions usually stabilized, but could also resolve completely (n = 2) or progress and lead to bone deformation. The most common complication of HPC was a fracture through the lesion (n = 7). Neither pamidronate nor indomethacin seemed to influence the course of HPC. CONCLUSIONS: HPC is a potentially serious complication of OI type V. Given the rarity of the disorder, treatment studies will require multicenter collaborations.
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Calo Ósseo/patologia , Osteogênese Imperfeita/classificação , Osteogênese Imperfeita/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Hiperplasia/patologia , Masculino , Pessoa de Meia-Idade , Tomógrafos ComputadorizadosRESUMO
Calcium and bone disorders in children and adolescents are treated with a wide variety of drugs. Several of these drugs have been used for many years on the basis of accepted practice, without being subjected to rigorous trials. Bisphosphonates are the mainstay treatment for children with osteoporosis, but newer, more potent compounds such as zoledronate and risedronate have begun to replace the older-generation bisphosphonates. Hypocalcaemia is managed with calcium and vitamin D and its metabolites. In difficult cases that are secondary to hypoparathyroidism, subcutaneous injections or infusions of parathyroid hormone have been used. Multiple daily phosphate supplements and calcitriol are the standard treatment for hypophosphataemic rickets, but trials of an anti-fibroblast growth factor 23 antibody appear promising, and the results are eagerly awaited. Many new medications are undergoing clinical trials and are starting to emerge as viable treatment options for children. Some of these drugs target specific diseases, such as recombinant alkaline phosphatase for hypophosphatasia and a C-type natriuretic peptide analogue for achondroplasia. Other drugs, such as denosumab and odanacatib, have been used successfully in the adult population, and the appropriate use of these drugs in children is now being evaluated.
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Conservadores da Densidade Óssea/uso terapêutico , Cálcio/uso terapêutico , Difosfonatos/uso terapêutico , Glucocorticoides/uso terapêutico , Hipercalcemia/tratamento farmacológico , Hipocalcemia/tratamento farmacológico , Osteoporose/tratamento farmacológico , Acetazolamida/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Osso e Ossos/metabolismo , Calcitonina/uso terapêutico , Calcitriol/uso terapêutico , Criança , Denosumab/uso terapêutico , Diuréticos/uso terapêutico , Humanos , Hiperfosfatemia/tratamento farmacológico , Hipofosfatemia/tratamento farmacológico , Imidazóis/uso terapêutico , Hormônio Paratireóideo , Fosfatos/uso terapêutico , Ácido Risedrônico/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Vitamina D/uso terapêutico , Ácido ZoledrônicoRESUMO
CONTEXT: Osteogenesis imperfecta (OI) type I is a heritable bone fragility disorder that is caused by mutations affecting collagen type I. We recently showed that patients with OI type I frequently have muscle weakness. As muscle force and bone mass are usually closely related, we hypothesized that muscle weakness in OI type I could contribute to increase bone mass deficit in the lower extremities. OBJECTIVE: To assess the muscle-bone relationship in the lower extremities of children and adolescents with OI type I. SETTING: The study was carried out in the outpatients department of a pediatric orthopedic hospital. Patients and other participants Thirty children and adolescents with OI type I (20 females; mean age [SD]: 11.2 years [3.9]) were compared with 30 healthy age- and sex-matched controls (mean age [SD]: 11.1 years [4.5]). MAIN OUTCOME MEASURES: Tibia bone mineral content (BMC; mg/mm) was measured by peripheral quantitative computed tomography to estimate bone strength at the 4% and 14% sites. Lower extremity peak force (kN) was measured by mechanography using the multiple two-legged hopping test. RESULTS: Compared with age- and sex-matched controls, patients with OI type I had 17% lower peak force (1.3 kN vs. 1.7 kN; p=0.002) as well as a 22% lower BMC (128 mg/mm vs. 165 mg/mm; p<0.001). Stepwise regression analysis showed that muscle force and tibia length were positively related to bone strength (r(2)=0.90, p<0.001) whereas there was no effect of the disease status (OI vs. control). CONCLUSIONS: These results suggest that the muscle-bone relationship is similar between children and adolescents with OI type I and healthy age and sex-matched controls. It also suggests that muscle weakness may contribute to decreased bone strength in individuals with OI type I.