Health-related quality of life and associated risk factors in patients with Multiple Osteochondromas: a cross-sectional study.

PURPOSE: To evaluate the health-related quality of life and associated risk factors for Multiple Osteochondromas patients. METHODS: A cross-sectional, observational study was conducted from May to December 2022 during the routine visit to the referral center for rare skeletal disorders. All patients with Multiple Osteochondromas aged ≥ 3 years were included. EuroQol 5-dimension questionnaires, and demographic, clinical, and surgical history data were collected. Descriptive statistics, Fisher's exact test, One-sample t-test, Spearman's correlation, and multiple linear and logistic regression were performed to analyze the data. Results are reported following STROBE guidelines. RESULTS: A total of 128 patients were included in the study, with a mean age of 14 [SD, 10] years. The mean EQ-5D Index Value was 0.863 [SD, 0.200] and the EQ-VAS was 84 [SD, 19] with a positive correlation between two scores [r = 0.541, p < 0.001]. Patients frequently referred problems in pain/discomfort [78.8%], anxiety/depression [50%], and usual activities [38.8%] dimensions. Increasing age was the common risk factor for health-related quality of life [p < 0.000], as well as Index Value and VAS scores were significantly lower in surgical patients [p = 0.001 and p < 0.001, respectively]. CONCLUSION: Increasing age and surgical procedures were found highly associated with reduced health-related quality of life in Multiple Osteochondromas patients. Our findings provide relevant information to support the establishment of patient-centered healthcare pathways and pave the way for further research into medical and non-medical therapeutic strategies for these patients.

Secondary peripheral chondrosarcoma in multiple osteochondromas: a retrospective single-institution case series.

BACKGROUND: Multiple osteochondromas is genetic disorder characterized by the formation of multiple benign cartilage-capped bone tumors, named osteochondromas, during skeletal development. The most feared complication is the secondary peripheral chondrosarcoma, a malignant cartilaginous neoplasm that arises from the chondroid cap of pre-existent osteochondromas. We conducted a retrospective cohort study on patients diagnosed and followed up from 1960 to 2019 to describe the clinical and pathological features of individuals affected by peripheral chondrosarcoma in multiple osteochondromas, to evaluate follow up information and individual outcome and to compare the results with literature. Data, including age, gender, site, histological grade, cartilage cap thickness, surgical treatments, surgical margins, genotype mutational status as well as treatment details were captured from the hospital electronic health records and from Registry of Multiple Osteochondromas. In addition, a complete histological review of all hematoxylin and eosin (H&E)-stained sections has been performed by expert pathologists. RESULTS: One hundred five of the screened cases were included in the present study. The age at diagnosis of SPC ranges from 13 to 63, with median age at diagnosis of 34 years. The site most frequently affected by malignant degeneration was the pelvis (46 patients, 44%) with higher incidence in male patients (32 males vs.14 females). The second one was lower limbs (including femur, fibula, or tibia), identified in 35 patients. Histological information - available for 103 patients - showed: 59 patients with grade 1; 40 patients had a grade 2 and 4 patients had a grade 3. The most common surgical treatment was the complete resection, followed by debulking, amputation and partial resection. Most of cases did not have recurrence of the disease. Outcome in disease-free survival highlights that a worse course of the disease was associated with histological grade 2 or 3, and partial resection surgery. In most of analyzed cases (94%) a pathogenic variant was identified. CONCLUSIONS: In conclusion, the present study gives an overview of the secondary peripheral chondrosarcomas, confirming that this disease represents an impacting complication for multiple osteochondromas patients and suggests that malignant transformation can occur also in younger patient, in a not irrelevant number of cases.

Pathological mandibular fracture complicated by osteonecrosis in an adult patient with pycnodysostosis: clinical report and review of the literature.

Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia, and increased caries) are also frequent; due to bone metabolism alteration, the patients have an increased risk for jaw osteomyelitis, especially after tooth extraction or mandible fracture. Other complications are obstructive sleep apnea, endocrine alterations and cytopenia. Pycnodysostosis is caused by biallelic loss of function variants in CTSK gene, coding the lysosomal protease cathepsin K. CTSK is involved in the degradation of bone matrix proteins, such as type I and type II collagen. In pycnodysostosis, this degradation is decreased, leading to increased bone density and bone fragility with pathological fractures and poor healing. We present a clinical report of a female adult patient with typical pycnodysostosis phenotype. At the age of 52 years, she had a pathological spontaneous fracture of the right mandible complicated by osteonecrosis, treated with load bearing osteosynthesis. The direct sequencing of CTSK gene revealed the presence of the pathogenic homozygous variant c.746T>A, (p.Ile249Asn), that confirmed the diagnosis of pycnodysostosis. We also review the literature case series published to date, that suggest to always consider the diagnosis of pycnodysostosis in case of osteosclerosis, even in the absence of brachydactyly or short stature. This report details the natural history of the disease in this patient, from childhood to adulthood, and highlights the importance of a quality of life assessment. In addition, we describe a case of mandibular osteonecrosis and spontaneous fracture in pycnodysostosis, drawing attention on the maxillofacial complications in these patients and on the importance of a personalized follow-up.

Vitamin D and Bone fragility in Individuals with Osteogenesis Imperfecta: A Scoping Review.

Vitamin D affects several body functions, and thus general health, due to its pleiotropic activity. It plays a key role in bone metabolism, and its deficiency impacts bone development, leading to bone fragility. In osteogenesis imperfecta (OI), a group of hereditary connective tissue disorders characterized by bone fragility, additional factors, such as vitamin D deficiency, can affect the expression of the phenotype and aggravate the disorder. The aim of this scoping review was to assess the incidence of vitamin D deficit in OI patients and the association between vitamin D status and supplementation in individuals affected by OI. We searched the PubMed Central and Embase databases and included studies published between January/2000 and October/2022 evaluating vitamin D measurement and status (normal, insufficiency, deficiency) and supplementation for OI. A total of 263 articles were identified, of which 45 were screened by title and abstract, and 10 were included after a full-text review. The review showed that low levels of vitamin D was a frequent finding in OI patients. Vitamin D supplementation was mainly indicated along with drug therapy and calcium intake. Even if widely used in clinical practice, vitamin D supplementation for OI individuals still needs a better characterization and harmonized frame for its use in the clinical setting, as well as further studies focusing on its effect on bone fragility.

Clinical-functional features of individuals with Osteogenesis Imperfecta and Ehlers-Danlos syndromes: A scoping review of assessment tools and ICF model.

BACKGROUND: Clinical-functional assessment of patients affected by Osteogenesis Imperfecta and Ehlers-Danlos Syndromes is essential for clinical management. However, there is no clear information on disease-specific tools of assessment for clinical practice, thus limiting quantification and management of the diseases-related impairments. OBJECTIVE: The present scoping review was aimed at investigating the most common clinical-functional features and assessment tools in individuals with Osteogenesis Imperfecta and Ehlers-Danlos Syndromes, and to provide an updated International Classification of Functioning (ICF) model related to functional impairments for each disease. METHODS: The literature revision was conducted on PubMed, Scopus and Embase databases. Articles reporting an ICF model of clinical-functional features and assessment tools for Osteogenesis Imperfecta and Ehlers-Danlos Syndromes individuals were included. RESULTS: A total of 27 articles were included, 7 reporting an ICF model, and 20 reporting clinical-functional assessment tools. It was reported that patients with Osteogenesis Imperfecta and Ehlers-Danlos Syndromes show impairments in both Body Function and Structure, and Activities and Participation domains of the ICF. A heterogeneous number of assessment tools was found for both diseases regarding proprioception, pain, endurance to exercise, fatigue, balance and motor coordination, and mobility. CONCLUSION: Patients with Osteogenesis Imperfecta and Ehlers-Danlos Syndromes show several impairments and limitations in Body Function and Structure, and Activities and Participation domains of the ICF. Thus, an appropriate and ongoing assessment of the disease-related impairments is necessary to improve clinical practice. Several functional tests and clinical scales can be used to assess the patients despite the heterogeneity of assessment tools found in previous literature.

Secondary peripheral chondrosarcoma arising in solitary osteochondroma: variables influencing prognosis and survival.

BACKGROUND: Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. METHODS: The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. RESULTS: Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69-8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69-8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57-8.79; p = 0.003) were associated with a significantly worse disease-free survival. CONCLUSIONS: Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma.

COL1-Related Disorders: Case Report and Review of Overlapping Syndromes.

Collagen type I mutations are related to wide phenotypic expressions frequently causing an overlap of clinical manifestations, in particular between Osteogenesis Imperfecta (OI) and Ehlers-Danlos syndrome (EDS). Both disorders present inter- and intra-familial clinical variability and several clinical signs are present in both diseases. Recently, after the observation that some individuals first ascertained by a suspicion of EDS resulted then carriers of pathogenic variants of genes known to primarily cause OI, some authors proposed the term "COL1-related overlap disorder" to describe these cases. In this paper, we report clinical, molecular, and biochemical information about an individual with a diagnosis of EDS with severe joint hypermobility who carries a pathogenic heterozygous variant in COL1A2 gene, and a benign variant in COL1A1 gene. The pathogenic variant, commonly ascribed to OI, as well as the benign variant, has been inherited from the individual's mother, who presented only mild signs of OI and the diagnosis of OI was confirmed only after molecular testing. In addition, we reviewed the literature of similar cases of overlapping syndromes caused by COL1 gene mutations. The reported case and the literature review suggest that the COL1-related overlap disorders (OI, EDS and overlapping syndromes) represent a continuum of clinical phenotypes related to collagen type I mutations. The spectrum of COL1-related clinical manifestations, the pathophysiology and the underlying molecular mechanisms support the adoption of the updated proposed term "COL1-related overlap disorder" to describe the overlapping syndromes.

Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation.

BACKGROUND: Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients. METHODS: Herein, we report a case of an 8-year- old child with Stickler Syndrome, presenting with early-onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene. RESULTS: A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing. CONCLUSION: We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early-onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene-related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease.

Cyclic pamidronate treatment for osteogenesis imperfecta: Report from a Brazilian reference center.

Treatment of moderate and severe forms of osteogenesis imperfecta (OI) with cyclic pamidronate at the Reference Center for OI Treatment in Southern Brazil was studied. A retrospective cohort study was conducted from 2002 to 2012. Data were obtained during inpatient (drug infusion) and outpatient care. Clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, history and site of the fractures, biochemical data, including calcium, phosphorus, and alkaline phosphatase levels, were systematically collected. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Forty-five patients (26 females) were included in the study, and the age of the patients at the time of diagnosis ranged from 1 to 144 months, with a median age (p25-p75) of 38 (5-96) months. Most cases presented OI-4 (51.1%), and the median age of the patients at the start of treatment was 3.3 years (25-75 percentiles: 0.5 - 8.7 years). Twenty-four patients (54.5%) had some adverse events or intercurrences during treatment, and the treatment compliance mean was 92.3% (± 10.7). The treatment with intravenous pamidronate has shown to be safe, well-tolerated, and effective in regard to the improvement of BMD and the reduction of the number of fractures in children and adolescents with OI.

Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series.

Melorheostosis (MEL) is an uncommon, sclerosing disease, characterised by hyperostosis of long bones, resembling the flowing of candle wax. The disease is sporadic and the pathogenesis is still poorly understood. Occasionally, the same family can include individuals with MEL and Osteopoikilosis (OPK), a disease characterised by multiple round foci of increased bone density. LEMD3 gene mutations are related to OPK and Buschke-Ollendorff Syndrome, a genetic condition in which an association between MEL, OPK and skin lesions is observed. In rare cases, LEMD3 mutations and recently mosaic MAP2K1 gene mutations have been correlated to MEL suggesting that somatic mosaicism could be causative of the disease. In this study, we described the clinical, radiological and molecular findings of 19 individuals with MEL and 8 with OPK and compared the results to the medical literature. The molecular analyses of this case series corroborate the available data in the medical literature, indicating that LEMD3 germline mutations are not a major cause of isolated MEL and reporting five further cases of OPK caused by LEMD3 germline mutations.

Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta.

On the occasion of the 13th International Conference on Osteogenesis imperfecta in August 2017 an expert panel was convened to develop an international consensus paper regarding physical rehabilitation in children and adolescents with Osteogenesis imperfecta. The experts were chosen based on their clinical experience with children with osteogenesis imperfecta and were identified by sending out questionnaires to specialized centers and patient organizations in 26 different countries. The final expert-group included 16 representatives (12 physiotherapists, two occupational therapists and two medical doctors) from 14 countries. Within the framework of a collation of personal experiences and the results of a literature search, the participating physiotherapists, occupational therapists and medical doctors formulated 17 expert-statements on physical rehabilitation in patients aged 0-18 years with osteogenesis imperfecta.

Health-related quality of life of children and adolescents with osteogenesis imperfecta: a cross-sectional study using PedsQL™.

BACKGROUND: Osteogenesis imperfecta (OI) is a disorder of bone formation leading to low mineral density and fractures. Children and adolescents with OI require periodic medical follow up, corrective surgery, drug therapy and physical therapy, as well as specific daily care practices. In addition, they have an increased incidence of fractures, which require immobilization and cause severe discomfort and short-term disability. This study evaluated the health-related quality of life of children and adolescents with OI in two reference centers for OI treatment in southern Brazil. METHODS: In this prospective cross-sectional study, the Pediatric Quality of Life Inventory (PedsQLTM) was applied in two university-affiliated reference centers for OI treatment in southern Brazil. Children and adolescents aged ≥ 5 years with clinical diagnoses of OI were included. Clinical data and socioeconomic status was evaluated. RESULTS: The sample consisted of 52 children and adolescents with OI (aged 5-17 years); 26 (50%) participants with type I OI, 13 (25%) type IV, 12 (23.1 %) type III, and 1 (1.9%) type V OI. Physical and social functioning domains differed significantly according to clinical presentation of OI with lowest scores in the severe type (OI type III). Pain seems to be the variable that is most associated with impact on the PedsQL domains. CONCLUSIONS: Overall, this study revealed differences in physical functioning and social functioning in relation to OI clinical presentation. These results reinforcing the importance of the clinical management of these patients with the aim of functional improvement and importance of pain control.

CLINICAL FEATURES AND PATTERN OF FRACTURES AT THE TIME OF DIAGNOSIS OF OSTEOGENESIS IMPERFECTA IN CHILDREN. / CARACTERÍSTICAS CLÍNICAS E PADRÃO DE FRATURAS NO MOMENTO DO DIAGNÓSTICO DE OSTEOGÊNESE IMPERFEITA EM CRIANÇAS.

OBJECTIVE: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. METHODS: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. RESULTS: Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. CONCLUSIONS: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.

OBJETIVO: Caracterizar o padrão de fraturas e a história clínica no momento do diagnóstico de osteogênese imperfeita. MÉTODOS: Neste estudo retrospectivo, foram incluídos todos os pacientes com osteogênese imperfeita de ambos os sexos, com idades entre 0 e 18 anos, que realizaram tratamento entre 2002 e 2014. Os prontuários médicos foram revisados para coleta de dados clínicos, incluindo presença de escleras azuladas, dentinogênese imperfeita, história familiar positiva para a doença e locais das fraturas, além de achados radiográficos no momento do diagnóstico. RESULTADOS: Foram incluídos no estudo 76 pacientes (42 do sexo feminino), com idade, no momento do diagnóstico, entre 0 e 114 meses [mediana (p25-p75) de idade de 38 (6-96) meses]. Escleras azuladas estavam presentes em 93,4% dos pacientes, dentinogênese imperfeita foi observada em 27,6% e ossos wormianos em 29,4%. O número de fraturas ao diagnóstico variou entre 0 e 17, com uma mediana de 3 (2-8) fraturas. Em 40 (57%) pacientes, as fraturas eram de membros superiores e inferiores no momento do diagnóstico e, em 9 pacientes também havia fratura vertebral. O diagnóstico foi realizado ao nascimento em 85,7% dos pacientes com o tipo 3 e em 39,3% daqueles com tipo 4/5 da doença. CONCLUSÕES: Osteogênese imperfeita é uma doença genética com características clínicas distintas, tais como fragilidade óssea, fraturas recorrentes, escleras azuladas e dentinogênese imperfeita. É importante saber identificar essas características, facilitando o diagnóstico, otimizando o tratamento e diferenciando de outras doenças que também podem causar fraturas.

Características clínicas e padrão de fraturas no momento do diagnóstico de osteogênese imperfeita em crianças / Clinical features and pattern of fractures at the time of diagnosis of osteogenesis imperfecta in children

RESUMO Objetivo: Caracterizar o padrão de fraturas e a história clínica no momento do diagnóstico de osteogênese imperfeita. Métodos: Neste estudo retrospectivo, foram incluídos todos os pacientes com osteogênese imperfeita de ambos os sexos, com idades entre 0 e 18 anos, que realizaram tratamento entre 2002 e 2014. Os prontuários médicos foram revisados para coleta de dados clínicos, incluindo presença de escleras azuladas, dentinogênese imperfeita, história familiar positiva para a doença e locais das fraturas, além de achados radiográficos no momento do diagnóstico. Resultados: Foram incluídos no estudo 76 pacientes (42 do sexo feminino), com idade, no momento do diagnóstico, entre 0 e 114 meses [mediana (p25-p75) de idade de 38 (6-96) meses]. Escleras azuladas estavam presentes em 93,4% dos pacientes, dentinogênese imperfeita foi observada em 27,6% e ossos wormianos em 29,4%. O número de fraturas ao diagnóstico variou entre 0 e 17, com uma mediana de 3 (2-8) fraturas. Em 40 (57%) pacientes, as fraturas eram de membros superiores e inferiores no momento do diagnóstico e, em 9 pacientes também havia fratura vertebral. O diagnóstico foi realizado ao nascimento em 85,7% dos pacientes com o tipo 3 e em 39,3% daqueles com tipo 4/5 da doença. Conclusões: Osteogênese imperfeita é uma doença genética com características clínicas distintas, tais como fragilidade óssea, fraturas recorrentes, escleras azuladas e dentinogênese imperfeita. É importante saber identificar essas características, facilitando o diagnóstico, otimizando o tratamento e diferenciando de outras doenças que também podem causar fraturas.

ABSTRACT Objective: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. Methods: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Results: Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Conclusions: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.

Health outcomes of neonates with osteogenesis imperfecta: a cross-sectional study.

OBJECTIVE: To assess at-birth health outcomes of neonates with osteogenesis imperfecta (OI). STUDY DESIGN: A total of 53 women who self-reported having had at least one child with OI completed the survey. We evaluated pregnancy length, neonatal intensive care unit (NICU) usage, at-birth complications, and the child's clinical information including OI type, height and weight. RESULTS: Information was gathered on a total of 77 children (60 type I, 4 type III and 13 type IV). Health conditions reported at birth included breech presentation (24%), prematurity (27%), fracture (18%), bone deformity (18%) and respiratory problems (22%). Approximately 31% (n = 24) received NICU care. There was a significant association between younger maternal age, preterm delivery and NICU admission. CONCLUSION: Our findings suggest that newborns with OI appear to be at high risk of skeletal disorders, preterm delivery and breech presentation. Younger maternal age and preterm delivery seem to be strong predictors of the need for NICU care. Our data suggest that pregnant women with OI younger than 20 years of age may benefit from added clinical supervision in anticipation of adverse effects on their child.

Study of the Determinants of Vitamin D Status in Pediatric Patients With Osteogenesis Imperfecta.

OBJECTIVE: Vitamin D is essential to the development and maintenance of the skeleton, especially for children with bone disorders such as osteogenesis imperfecta (OI). We evaluated serum 25-hydroxyvitamin D (25-OHD) levels to assess the relationship between determinants of vitamin D status in pediatric patients with OI. METHODS: This cross-sectional study evaluated sex, age, weight, height, body mass index, OI type, sunscreen use, season of assessment, sun exposure, vitamin D and calcium supplementation, bisphosphonate treatment, bone mineral density (BMD), milk and soda consumption, mobility, and time of sedentary activity. Levels of serum 25-OHD, calcium, parathyroid hormone (PTH), phosphorus, and alkaline phosphatase (ALP) were analyzed. Serum levels of 25-OHD were classified according to sufficient (>30 ng/ml or 75 nmol/L), insufficient (20-30 ng/ml or 50-75 nmol/L), moderately deficient (20-10 ng/ml or 50-25 nmol/L), and severely deficient (<10 ng/ml or 25 nmol/L). RESULTS: Fifty-two patients were included and 46 (88.4%) were classified as having insufficient or deficient 25-OHD. An inverse correlation between serum 25-OHD and time of sedentary activity (r = -0.597, p < 0.001) and a positive correlation with height (r = 0.521, p = 0.046) and whole body BMD (r = 0.586, p = 0.022) were observed. A significant difference between the number of glasses of milk consumed (p = 0.010) was observed. CONCLUSION: To optimize bone health, patients with OI need to be educated regarding habits that can improve serum 25-OHD levels, such as a reduction in periods of inactivity, the importance of sun exposure, and increasing consumption of milk and fortified dairy products.

Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V.

Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5'UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity.

Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta.

BACKGROUND: Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. METHODS: Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. RESULTS: An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. CONCLUSION: The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI.

Bisphosphonate treatment of children and adults with osteogenesis imperfecta: unanswered questions.

Bisphosphonates are extensively used for treatment of children and adults with osteogenesis imperfecta. Over years, studies have reported the response of BP treatment in individuals with OI but some questions remain still unanswered.