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Revue Medicale de Liege Jan 2009We report the case of a young boy who had had multiple bone fractures (more than 10) since the age of 19 months. The father had the same clinical history. The clinical...
We report the case of a young boy who had had multiple bone fractures (more than 10) since the age of 19 months. The father had the same clinical history. The clinical examination was normal for his age except blue sclera. The bone densitometry showed a severe osteoporosis for his age. Biological exam swere correct. The genetic exploration revealed mutation of COL1A2 gene. With this clinical history, the diagnosis of Osteogenesis imperfecta (OI) was retained. OI is a hereditary dystrophy with abnormal synthesis or metabolism of collagen with, often, mutation of COL1A1 or COL1A2 genes. There are 7 different forms. We consider the possible differential diagnoses. The goal of any treatment is to promote bone remineralisation and to decrease the fracture frequency. The treatment includes calcium and vitamin D, and in the presence of some precise criteria, biphosphonate therapy.
Topics: Bone Density; Calcium; Chromosome Mapping; Collagen; Collagen Type I; Collagen Type I, alpha 1 Chain; Diagnosis, Differential; Diphosphonates; Drug Therapy, Combination; Humans; Infant; Male; Mutation; Osteogenesis Imperfecta; Pedigree; Treatment Outcome; Vitamin D
PubMed: 19317096
DOI: No ID Found -
Journal of Orthopaedic Surgery and... Jun 2023Osteogenesis imperfecta is a genetic disorder leading to multiple fractures and deformities. Intramedullary rods have been used in the surgical treatment of osteogenesis...
Fixation techniques in lower extremity correction osteotomies and fractures in mild-to-severe osteogenesis imperfecta patients: evaluation of the results and complications.
INTRODUCTION
Osteogenesis imperfecta is a genetic disorder leading to multiple fractures and deformities. Intramedullary rods have been used in the surgical treatment of osteogenesis imperfecta for decades. Complication rates reported by current techniques have been high. This study aimed to examine the results of intramedullary fixation combined with plate and screw technique in patients with osteogenesis imperfecta compared to isolated intramedullary fixation.
METHODS
Between 2006 and 2020, forty patients who had surgical treatment for deformities or fractures of the femur, tibia or both with at least two years of follow-up after surgery were included in the study. Patients were divided into groups according to fixation methods. Group 1 was intramedullary fixation only (Titanium Elastic Nail [TEN], Rush Pin, and Fassier-Duval Rod), and Group 2 was intramedullary fixation combined with plate and screws. Medical records and follow-up radiographs were reviewed to evaluate healing and callus formation, types of complications and infection rates.
RESULTS
The total number of operated lower extremities of these forty patients was 61 (45 femur and 16 tibia). The mean age of the patients was 9.3 ± 4.6 years. Mean follow-up duration of the patients was 4.4 ± 1.7 years. Thirty-seven (61%) were in Group 1, and 24 (39%) were in Group 2. There was no statistically significant difference in callus formation time between Group 1 and Group 2 (p = 0.67). Complications occurred in 21 of 61 surgeries. While 17 of these complications were in Group 1, 4 were in Group 2 (p = 0.01).
CONCLUSION
Intramedullary fixation combined with the plate and screw technique in children with osteogenesis imperfecta is successful considering the complications and revision requirements.
Topics: Child; Humans; Child, Preschool; Adolescent; Osteogenesis Imperfecta; Fracture Fixation, Intramedullary; Fractures, Bone; Bone Plates; Osteotomy; Lower Extremity; Bone Nails
PubMed: 37328762
DOI: 10.1186/s13018-023-03917-z -
International Journal of Molecular... Jan 2021Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone... (Review)
Review
Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding the mechanism of rare genetic bone fragility disorders not only advances medical knowledge on rare diseases, it may open doors for drug development for more common disorders (i.e., postmenopausal osteoporosis). In this review, we highlight the main disease mechanisms underlying the development of human bone fragility associated with low bone mass known to date. The pathways we focus on are type I collagen processing, WNT-signaling, TGF-ß signaling, the RANKL-RANK system and the osteocyte mechanosensing pathway. We demonstrate how the discovery of most of these pathways has led to targeted, pathway-specific treatments.
Topics: Collagen Type I; Humans; Osteogenesis Imperfecta; Osteoporosis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Transforming Growth Factor beta; Wnt Signaling Pathway
PubMed: 33435159
DOI: 10.3390/ijms22020625 -
Scientific Reports Oct 2022About 70% of people with osteogenesis imperfecta (OI) experience hearing loss. There is no cure for OI, and therapies to ameliorate hearing loss rely on conventional... (Meta-Analysis)
Meta-Analysis
About 70% of people with osteogenesis imperfecta (OI) experience hearing loss. There is no cure for OI, and therapies to ameliorate hearing loss rely on conventional treatments for auditory impairments in the general population. The success rate of these treatments in the OI population with poor collagenous tissues is still unclear. Here, we conduct a systematic review and meta-analysis on the efficacy of treatments addressing hearing loss in OI. This study conforms to the reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Data sources include published articles in Medline via PubMed, Web of Science, Scopus, and Embase, from their inception to November 2020. Studies included individuals with OI undergoing a hearing loss treatment, having pre- and postoperative objective assessment of hearing function at a specified follow-up length. Our search identified 1144 articles, of which 67 were reviewed at full-text screening. A random-effects meta-analysis was conducted on the selected articles (n = 12) of people with OI that underwent stapes surgery. Success was assessed as the proportion of ears with a postoperative Air-Bone Gap (ABG) ≤ 10 dB. A systematic review was conducted on the remaining articles (n = 13) reporting on other treatments. No meta-analysis was conducted on the latter due to the low number of articles on the topic and the nature of single case studies. The meta-analysis shows that stapes surgeries have a low success rate of 59.08 (95% CI 45.87 to 71.66) in the OI population. The systematic review revealed that cochlear implants, bone-anchored hearing aids, and other implantable hearing aids proved to be feasible, although challenging, in the OI population, with only 2 unsuccessful cases among the 16 reviewed single cases. This analysis of published data on OI shows poor clinical outcomes for the procedures addressing hearing loss. Further studies on hearing loss treatments for OI people are needed. Notably, the mechanisms of hearing loss in OI need to be determined to develop successful and possibly non-invasive treatment strategies.
Topics: Cochlear Implantation; Deafness; Hearing Loss; Humans; Osteogenesis Imperfecta; Stapes Surgery
PubMed: 36224204
DOI: 10.1038/s41598-022-20169-9 -
Graefe's Archive For Clinical and... Sep 2023Osteogenesis imperfecta (OI) is a rare inherited disease affecting collagen-rich tissues. Ocular complications have been reported such as thin corneas, low ocular...
PURPOSE
Osteogenesis imperfecta (OI) is a rare inherited disease affecting collagen-rich tissues. Ocular complications have been reported such as thin corneas, low ocular rigidity, keratoconus, among others. The purpose of this study is to characterize corneal tomographic features in OI patients compared to unaffected patients, with particular focus on commonly studied keratoconus indices.
METHODS
Cross-sectional case-control study including 37 OI patients and 37 age-matched controls. Patients and controls underwent comprehensive ophthalmological examination including corneal Scheimpflug tomography with a Pentacam HR device (Oculus Optikgeräte GmbH, Wetzlar, Germany) to analyse and compare topometric, tomographic, pachymetric and Belin-Ambrósio Enhanced Ectasia Display III (BAD-D) data of both eyes of each patient.
RESULTS
Most OI patients had type I disease (n = 24; 65%) but type III-VII patients were also included. Two patients had clinically overt bilateral keratoconus. OI patients had significantly higher maximum keratometry (45.2 ± 2.1 vs. 43.7 ± 1.2; p = 0.0416), front and back elevation (3.0 ± 3.3 vs. 2.1 ± 1.3, p = 0.0201; 11.1 ± 8.2 vs. 5.0 ± 3.7, p < 0.0001), index of surface variance (25.5 ± 13 vs. 17.4 ± 8.3; p = 0.0016), index of vertical asymmetry (0.21 ± 0.14 vs. 0.15 ± 0.06; p = 0.0215), index of height asymmetry (9.2 ± 14 vs. 6.0 ± 4.5; p = 0.0421), index of height decentration (0.02 ± 0.01 vs. 0.01 ± 0.01; p < 0.0001) and average pachymetric progression (1.01 ± 0.19 vs. 0.88 ± 0.14; p < 0.0001) readings. Thinnest corneal thickness and maximum Ambrósio relational thickness were significantly lower (477 ± 52 vs. 543 ± 26; 387 ± 95 vs. 509 ± 49; p < 0.0001). Two-thirds of OI patients had corneas with a minimum thickness < 500 µm. BAD-D value was significantly higher in OI patients (2.1 ± 1.4 vs. 0.9 ± 0.2; p < 0.0001).
CONCLUSION
OI patients showed significant changes in corneal profiles compared with healthy subjects. A high proportion of patients had tomographically suspect corneas when using keratoconus diagnostic indices. Further studies are warranted to assess the true risk of corneal ectasia in OI patients.
Topics: Humans; Keratoconus; Corneal Topography; Case-Control Studies; Corneal Pachymetry; Osteogenesis Imperfecta; Dilatation, Pathologic; Cross-Sectional Studies; ROC Curve; Cornea; Tomography; Retrospective Studies
PubMed: 37074408
DOI: 10.1007/s00417-023-06059-4 -
Journal of the Mechanical Behavior of... May 2021Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In...
Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In this study, we hypothesized that deficient intrafibrillar mineralization is a key contributor to the OI induced bone brittleness. To test this hypothesis, we explored the mechanical and ultrastructural changes in OI bone using the osteogenesis imperfecta murine (oim) model. Synchrotron X-ray scattering experiments indicated that oim bone had much less intrafibrillar mineralization than wild type bone, thus verifying that the loss of mineral crystals indeed primarily occurred in the intrafibrillar space of oim bone. It was also found that the mineral crystals were organized from preferentially in longitudinal axis in wild type bone to more randomly in oim bone. Moreover, it revealed that the deformation of mineral crystals was more coordinated with collagen fibrils in wild type than in oim bone, suggesting that the load transfer deteriorated between the two phases in oim bone. The micropillar test revealed that the compression work to fracture of oim bone (8.2 ± 0.9 MJ/m) was significantly smaller (p < 0.05) than that of wild type bone (13.9 ± 2.7 MJ/m), while the bone strength was not statistically different (p > 0.05) between the two genotype groups. In contrast, the uniaxial tensile test showed that the ultimate strength of wild type bone (50 ± 4.5 MPa) was significantly greater (p < 0.05) than that of oim bone (38 ± 5.3 MPa). Furthermore, the nanoscratch test showed that the toughness of oim bone was much less than that of wild type bone (6.6 ± 2.2 GJ/m vs. 12.6 ± 1.4 GJ/m). Finally, in silico simulations using a finite element model of sub-lamellar bone confirmed the links between the reduced intrafibrillar mineralization and the observed changes in the mechanical behavior of OI bone. Taken together, these results provide important mechanistic insights into the underlying cause of poor mechanical quality of OI bone, thus pave the way toward future treatments of this brittle bone disease.
Topics: Animals; Calcinosis; Disease Models, Animal; Fractures, Bone; Mice; Osteogenesis Imperfecta; Radiography
PubMed: 33636677
DOI: 10.1016/j.jmbbm.2021.104377 -
Journal of Bone and Mineral Research :... Apr 2021Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility....
Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-β superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild-moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Bone and Bones; Collagen Type I; Disease Models, Animal; Female; Male; Mice; Myostatin; Osteogenesis; Osteogenesis Imperfecta
PubMed: 33249643
DOI: 10.1002/jbmr.4223 -
BMC Pediatrics Jan 2021Osteogenesis imperfecta(OI) is a frequent bone fragility disorder in children. The purpose of this study was to assess the BMD and Vitamin D level in children with OI in...
BACKROUND
Osteogenesis imperfecta(OI) is a frequent bone fragility disorder in children. The purpose of this study was to assess the BMD and Vitamin D level in children with OI in southern Iran.
METHOD
This case-control study was conducted on 23 children, clinically diagnosed as osteogenesis imperfecta and 23 age- and gender-matched healthy controls. Demographic and anthropometric data, biochemical parameters, puberty, sun exposure and physical activity were assessed. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry (DXA). Data analysis was done by SPSS22.
RESULTS
Forty-three point four percent of OI patients and fifty-six point five percent of control group had vitamin D deficiency (P = 0.376). Thirteen OI patients (56%) had low bone mass for chronological age in lumbar area (P < 0.001). Fracture episodes during treatment was significantly influenced by time of Pamidronate start, courses of Pamidronate injection, puberty and sun exposure (P values = 0.015, 0.030, 0.044 and 0.032, respectively). Fracture episodes during treatment had significantly increased in patients who had received Pamidronate more than 3 years compared with those received less than 3 years(P values = 0.047).
CONCLUSIONS
This study showed that vitamin D deficiency is prevalent amongst OI children in southern Iran. More than half of the OI children had low bone mass for chronological age in lumbar area, despite receiving bisphosphonate therapy. The present results revealed that early initiation of Pamidronate and number of Pamidronate courses are associated with lower fracture rate. However, treatment period more than 3 years can have adverse effect on fracture rates.
Topics: Adolescent; Bone Density; Case-Control Studies; Child; Diphosphonates; Fractures, Bone; Humans; Iran; Osteogenesis Imperfecta
PubMed: 33446151
DOI: 10.1186/s12887-020-02491-1 -
Endocrine Practice : Official Journal... Aug 2022To evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI).
OBJECTIVE
To evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI).
METHODS
We established a Chinese hospitalized cohort with OI and followed them up for an average of 6 years. All patients were confirmed as having OI using whole-exome sequencing. We analyzed the genotype-phenotype relationship based on different types, pathogenic mechanisms, and gene inheritance patterns of OI. Additionally, we assessed whether there was a difference in treatment efficacy based on genotype.
RESULTS
One hundred sixteen mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with type I, III, IV, V, VI, XI, or XV OI. Compared with patients with COL1A1 mutations, patients with COL1A2 mutations were younger at the time of the first fracture, whereas other phenotypes were similar. When 3 groups (helical, haploinsufficiency, and non-collagen I gene mutations) were compared, patients with helical mutations were the shortest and most prone to dentinogenesis imperfecta. Patients with haploinsufficiency mutations were the oldest at the time of the first fracture. Moreover, patients with non-collagen I gene mutations were least susceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences among non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of patients with OI, and the treatment effect appeared to be unrelated to their genotypes.
CONCLUSION
Our findings indicated a genotype-phenotype relationship and a similar effect of pamidronate treatment in patients with OI, which could provide a basis for guiding clinical treatment and predicting OI prognosis.
Topics: China; Collagen Type I; Follow-Up Studies; Genotype; Humans; Mutation; Osteogenesis Imperfecta; Pamidronate; Phenotype
PubMed: 35550181
DOI: 10.1016/j.eprac.2022.05.003 -
Bone Apr 2020As a dedicated experimentalist, John Currey praised the high potential of finite element (FE) analysis but also recognized its critical limitations. The application of... (Review)
Review
As a dedicated experimentalist, John Currey praised the high potential of finite element (FE) analysis but also recognized its critical limitations. The application of the FE methodology to bone tissue is reviewed in the light of his enthusiastic and colorful statements. In the past decades, FE analysis contributed substantially to the understanding of structure-function properties in the hierarchical organization of bone and to the simulation of bone adaptation. The systematic experimental validation of FE analysis of bone strength in anatomical locations at risk of fracture led to its application in clinical studies to evaluate efficacy of antiresorptive or anabolic treatment of bone fragility. Beyond the successful analyses of healthy or osteoporotic bone, FE analysis becomes increasingly involved in the investigation of other fragility-related bone diseases. The case of osteogenesis imperfecta (OI) is exposed, the multiscale alterations of the bone tissue and the effect of treatment summarized. A few FE analyses attempting to answer open questions in OI are then reported. An original study is finally presented that explored the structural properties of the Brtl/+ murine model of OI type IV subjected to sclerostin neutralizing antibody treatment using microFE analysis. The use of identical material properties in the four-point bending FE simulations of the femora reproduced not only the experimental values but also the statistical comparisons examining the effect of disease and treatment. Further efforts are needed to build upon the extraordinary legacy of John Currey and clarify the impact of different bone diseases on the hierarchical mechanical properties of bone.
Topics: Animals; Bone Density; Bone and Bones; Femur; Finite Element Analysis; Fractures, Bone; Mice; Osteogenesis Imperfecta
PubMed: 31981754
DOI: 10.1016/j.bone.2020.115250