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Nutrients Jun 2024A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD)....
BACKGROUND
A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was to evaluate the nutritional behavior of patients with RBD.
METHODS
This single-center, cross-sectional, questionnaire-based study assessed the nutritional behavior of RBD patients (X-linked hypophosphatemia (XLH), osteogenesis imperfecta (OI), hypophosphatasia (HPP)), osteoporosis (OPO) patients and healthy controls (CTRL). The nutritional questionnaire comprised 25 questions from seven nutritional areas. The associations between socioeconomic factors and BMI were assessed by age-adjusted univariate analysis of covariance (ANCOVA).
RESULTS
Fifty patients with RBD (17 OI, 17 HPP, 16 XLH; mean age of 48.8 ± 15.9, 26.0% male, mean BMI 26.2 ± 5.6), 51 with OPO (mean age 66.6 ± 10.0, 9.8% male, mean BMI 24.2 ± 3.9) and 52 CTRL (mean age 50.8 ± 16.3, 26.9% male, mean BMI 26.4 ± 4.7) participated. Twenty-six (52.0%) RBD, 17 (33.4%) OPO and 24 (46.1%) CTRL were overweight or obese according to BMI. Only a minority of RBD, OPO and CTRL had a daily intake of at least three portions of milk or milk products (17.3% RBD, 15.6% OPO, 11.6% CTRL, = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption ( = 0.016), fruit/vegetable juice consumption ( = 0.034), portions of fish per week ( = 0.044), high-fat meals per week ( = 0.015) and consumption of salty snacks ( = 0.001).
CONCLUSION
Nutritional counseling, controlling BMI and ensuring sufficient calcium and protein intake are crucial in patients with osteoporosis as well as in rare bone diseases. Vitamin D does not appear to be sufficiently supplied by the diet, and therefore supplementation should be considered in patients with bone diseases.
Topics: Humans; Cross-Sectional Studies; Male; Female; Middle Aged; Austria; Adult; Aged; Bone Diseases; Surveys and Questionnaires; Body Mass Index; Osteoporosis; Feeding Behavior; Nutritional Status; Diet
PubMed: 38931274
DOI: 10.3390/nu16121920 -
Journal of Clinical Medicine Jun 2024Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen... (Review)
Review
Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen fibers. Its predominant skeletal complication is scoliosis, impacting 25 to 80% of OI patients. Vertebral deformities of the scoliotic curves in OI include a variety of malformations such as codfish, wedged-shaped vertebrae or platyspondyly, craniocervical junction abnormalities, and lumbosacral spondylolysis and spondylolisthesis. Although the precise pathophysiology of these spinal deformities remains unclear, anomalies in bone metabolism have been implicated in the progression of scoliotic curves. Bone Mineral Density (BMD) measurements have demonstrated a significant reduction in the Z-score, indicating osteoporosis and a correlation with the advancement of scoliosis. Factors such as increased mechanical strains, joint hypermobility, lower leg length discrepancy, pelvic obliquity, spinal ligament hypermobility, or vertebrae microfractures may also contribute to the severity of scoliosis. Histological vertebral analysis has confirmed that changes in trabecular microarchitecture, associated with inadequate bone turnover, indicate generalized bone metabolic defects in OI. At the molecular level, the upregulation of Transforming Growth factor-β (TGFβ) signaling in OI can lead to disturbed bone turnover and changes in muscle mass and strength. Understanding the relationship between spinal clinical features and molecular pathways could unveil TGFβ -related molecular targets, paving the way for novel therapeutic approaches in OI.
PubMed: 38930011
DOI: 10.3390/jcm13123484 -
Genes May 2024Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I),...
Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. This study analyzed the clinical-genetic characteristics of patients with these conditions, focusing on both known and newly identified variants. We examined data from 15 patients, presenting symptoms of OI and joint contractures. Diagnostic methods included genealogical analysis, clinical assessments, radiography, whole exome sequencing, and direct automated Sanger sequencing. We diagnosed 15 patients with phenotypes due to biallelic variants-4 with OI Type XI, 10 with BS I, and 1 with the AG-like phenotype-demonstrating polymorphism in disease severity. Ten pathogenic variants were identified, including three novel ones, c.1373C>T (p.Pro458Leu), c.21del (p.Pro7fs), and c.831_832insCG (p.Gly278Argfs), and a recurrent variant, c.831dup (p.Gly278Argfs). Variant c.1490G>A (p.Trp497Ter) was found in two unrelated patients, causing OI XI in one and BS I in the other. Additionally, two unrelated patients with BS I and epidermolysis bullosa shared identical homozygous and variants. This observation illustrates the diversity of -related pathology and the importance of considering the full spectrum of phenotypes in clinical diagnostics.
Topics: Humans; Tacrolimus Binding Proteins; Male; Female; Arthrogryposis; Phenotype; Osteogenesis Imperfecta; Child; Child, Preschool; Pedigree; Exome Sequencing; Adolescent; Mutation; Infant; Adult; Nervous System Malformations
PubMed: 38927610
DOI: 10.3390/genes15060674 -
Cureus May 2024Osteogenesis imperfecta (OI) is a rare inherited skeletal disease, characterized by bone fragility and low bone density. There are several types of OI, varying in...
Osteogenesis imperfecta (OI) is a rare inherited skeletal disease, characterized by bone fragility and low bone density. There are several types of OI, varying in severity from benign to severe. We report a case of type II OI, which is a lethal form according to the Sillence classification. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. The genetic analysis was done along with genetic counseling. Death occurred on day nine of life due to respiratory failure secondary to pulmonary hypoplasia.
PubMed: 38910652
DOI: 10.7759/cureus.60945 -
Orphanet Journal of Rare Diseases Jun 2024Osteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and...
BACKGROUND
Osteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and extra-skeletal symptoms that results in an impairment of health-related quality of life of OI patients. Since published studies on OI in Spain are limited, this study aimed to determine the epidemiology, assessed the disease burden, management and unmet needs of OI patients in Spain. Thirty-four experts in the management of patients with osteogenesis imperfecta completed two rounds of online consultation and reported real-life experience and data from Spanish hospitals. Delphi study questionnaires were based on literature review. A working group of nationally recognized clinical experts supported the development of the study questionnaires and the final validation of results.
RESULTS
The estimated prevalence of patients diagnosed with OI in Spain is 0.56:10,000 inhabitants (95%CI: 0.54-0.59), which represents that, approximately, 2,669 OI patients are currently managed in Spanish hospitals. It is estimated that approximately 269 new patients would be diagnosed with OI each year in Spain, representing an estimated incidence of 0.06 (95%CI: 0.05-0.06) per 10,000 inhabitants per year. Clinical management of OI in Spain is performed by a range of medical specialists; however, multidisciplinary care is not fully implemented. The absence of an approved curative treatment or a treatment to reduce the clinical features of the disease remains the main unmet need.
CONCLUSIONS
This study provides a snapshot of the current situation of patients with OI in Spain reported by clinical experts. The results provide an estimation of the epidemiology of the disease, and complement the available evidence on disease burden, clinical management, and unmet needs of these patients in Spain.
Topics: Osteogenesis Imperfecta; Humans; Spain; Delphi Technique; Surveys and Questionnaires; Quality of Life; Female; Male; Prevalence
PubMed: 38890698
DOI: 10.1186/s13023-024-03248-0 -
BMC Musculoskeletal Disorders Jun 2024The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare...
BACKGROUND
The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children.
METHODS
This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests.
RESULTS
20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm, p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm, p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively).
CONCLUSIONS
Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children.
Topics: Humans; Osteogenesis Imperfecta; Male; Female; Child; Retrospective Studies; Case-Control Studies; Tomography, X-Ray Computed; Muscle, Skeletal; Adolescent; COVID-19; Radiation Dosage; Child, Preschool
PubMed: 38890605
DOI: 10.1186/s12891-024-07596-7 -
The Journal of Clinical Investigation Jun 2024Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes...
Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes in addition to bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in IFITM5. Here, we generated a conditional Rosa26 knock-in mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in OI type V patients. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with increase in the skeletal progenitor population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 showed decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupts early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.
PubMed: 38885336
DOI: 10.1172/JCI170369 -
The American Surgeon Jun 2024Musicians with physical disabilities who achieved stardom are part of the lore of popular music. Guitarist Django Reinhardt contrived alternate fingering patterns...
Musicians with physical disabilities who achieved stardom are part of the lore of popular music. Guitarist Django Reinhardt contrived alternate fingering patterns necessitated by burn contractures of his left hand. Les Paul, a legend in the development of the solid body electric guitar and multitrack recording, mangled his right arm in a car wreck so severely that his elbow was set permanently at 90° so he could continue to play guitar. Michel Petrucciani suffered from osteogenesis imperfecta, a condition that stunted his growth to the point where he used a special attachment to reach the sustaining pedals of his piano. Their stories show the force of human genius in music.
PubMed: 38869229
DOI: 10.1177/00031348241259307 -
The Journal of International Medical... Jun 2024Pregnant women with severe osteogenesis imperfecta (OI) are uncommon, and there are limited data regarding anaesthesia for caesarean section in these high-risk...
Pregnant women with severe osteogenesis imperfecta (OI) are uncommon, and there are limited data regarding anaesthesia for caesarean section in these high-risk individuals. The presence of anatomical and physiological abnormalities can pose technical challenges for the anaesthetist. This report describes the successful implementation of epidural anaesthesia in a parturient with severe OI. To our knowledge, this is the first documented use of ultrasound-assisted neuraxial anaesthesia and wrist blood pressure monitoring in such patients undergoing caesarean section. Understanding the pathophysiological changes associated with OI is crucial for ensuring safe administration of anaesthesia to these women.
Topics: Humans; Osteogenesis Imperfecta; Female; Pregnancy; Cesarean Section; Adult; Pregnancy Complications; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthetists
PubMed: 38863132
DOI: 10.1177/03000605241260551 -
BMJ Open Jun 2024Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile,...
An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: the BOOSTB4 trial protocol.
INTRODUCTION
Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4.
METHODS AND ANALYSIS
BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in or can be included in the trial.Each subject receives four intravenous doses of 3×10/kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover.
ETHICS AND DISSEMINATION
The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals.
TRIAL REGISTRATION NUMBERS
EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.
Topics: Humans; Osteogenesis Imperfecta; Female; Pregnancy; Mesenchymal Stem Cell Transplantation; Infant; Clinical Trials, Phase I as Topic; Multicenter Studies as Topic; Infant, Newborn; Clinical Trials, Phase II as Topic; Mesenchymal Stem Cells; Treatment Outcome; Male; Fetal Stem Cells
PubMed: 38834319
DOI: 10.1136/bmjopen-2023-079767