Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass, caused mainly by mutations in collagen type I encoding genes. The current study aimed to evaluate dentinogenesis imperfecta (DI), oral manifestations and caries status of OI children. Sixty-eight children (41 males, 27 females) aged from 3 to 17 years old (mean 9 ± 4.13) participated in the study. Participants were classified into three OI type groups (I—2 cases, III—31 cases and IV—35 cases). Clinical examination and an orthopantomogram were used to obtain prevalences and associations of DI, caries status, malocclusion, crossbite, open bite, eruption, impaction and missing teeth with OI. The prevalence of DI among OI patients was 47.1%, more common in OI type III than type IV. The yellow-brown discoloration type was more vulnerable to attrition than the opalescent-grey one in the primary dentition. OI seemed not to have a high risk of caries; the prevalence of caries was 69.1%. A high incidence of malocclusion, crossbite and open bite was observed. In-depth oral information would provide valuable data for better dental management in OI patients. Parents and general doctors should pay more attention to dental care to prevent caries and premature tooth loss.

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Osteogenesis imperfecta: potential therapeutic approaches

PeerJ ◽

10.7717/peerj.5464 ◽

2018 ◽

Vol 6 ◽

pp. e5464 ◽

Cited By ~ 4

Author(s):

Maxime Rousseau ◽

Jean-Marc Retrouvey ◽

Keyword(s):

Osteogenesis Imperfecta ◽

Scientific Evidence ◽

Genetic Disorder ◽

Collagen Type I ◽

Team Approach ◽

Type I ◽

Full Coverage ◽

Preliminary Examination ◽

Zirconia Crowns ◽

Intravenous Bisphosphonate

Osteogenesis imperfecta (OI) is a genetic disorder that is usually caused by disturbed production of collagen type I. Depending on its severity in the patient, this disorder may create difficulties and challenges for the dental practitioner. The goal of this article is to provide guidelines based on scientific evidence found in the current literature for practitioners who are or will be involved in the care of these patients. A prudent approach is recommended, as individuals affected by OI present with specific dentoalveolar problems that may prove very difficult to address. Recommended treatments for damaged/decayed teeth in the primary dentition are full-coverage restorations, including stainless steel crowns or zirconia crowns. Full-coverage restorations are also recommended in the permanent dentition. Intracoronal restorations should be avoided, as they promote structural tooth loss. Simple extractions can also be performed, but not immediately before or after intravenous bisphosphonate infusions. Clear aligners are a promising option for orthodontic treatment. In severe OI types, such as III or IV, orthognathic surgery is discouraged, despite the significant skeletal dysplasia present. Given the great variations in the severity of OI and the limited quantity of information available, the best treatment option relies heavily on the practitioner’s preliminary examination and judgment. A multidisciplinary team approach is encouraged and favored in more severe cases, in order to optimize diagnosis and treatment.

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Calvaria Bone Transcriptome in Mouse Models of Osteogenesis Imperfecta

International Journal of Molecular Sciences ◽

10.3390/ijms22105290 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5290

Author(s):

Pierre Moffatt ◽

Iris Boraschi-Diaz ◽

Juliana Marulanda ◽

Ghalib Bardai ◽

Frank Rauch

Keyword(s):

Osteogenesis Imperfecta ◽

Mouse Models ◽

Transforming Growth Factor Beta ◽

Collagen Type ◽

Transforming Growth Factor ◽

Collagen Type I ◽

Bone Fragility ◽

Type I ◽

Growth Factor Beta ◽

Upregulated Genes

Osteogenesis imperfecta (OI) is a bone fragility disorder that is usually caused by mutations affecting collagen type I. We compared the calvaria bone tissue transcriptome of male 10-week-old heterozygous Jrt (Col1a1 mutation) and homozygous oim mice (Col1a2 mutation) to their respective littermate results. We found that Jrt and oim mice shared 185 differentially expressed genes (upregulated: 106 genes; downregulated: 79 genes). A total of seven genes were upregulated by a factor of two or more in both mouse models (Cyp2e1, Slc13a5, Cgref1, Smpd3, Ifitm5, Cthrc1 and Rerg). One gene (Gypa, coding for a blood group antigen) was downregulated by a factor of two or more in both OI mouse models. Overrepresentation analyses revealed that genes involved in ‘ossification’ were significantly overrepresented among upregulated genes in both Jrt and oim mice, whereas hematopoietic genes were downregulated. Several genes involved in Wnt signaling and transforming growth factor beta signaling were upregulated in oim mice, but less so in Jrt mice. Thus, this study identified a set of genes that are dysregulated across various OI mouse models and are likely to play an important role in the pathophysiology of this disorder.

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Novel Mutations Within Collagen Alpha1(I) and Alpha2(I) Ligand-Binding Sites, Broadening the Spectrum of Osteogenesis Imperfecta – Current Insights Into Collagen Type I Lethal Regions

Frontiers in Genetics ◽

10.3389/fgene.2021.692978 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kinga Sałacińska ◽

Iwona Pinkier ◽

Lena Rutkowska ◽

Danuta Chlebna-Sokół ◽

Elżbieta Jakubowska-Pietkiewicz ◽

...

Keyword(s):

Ligand Binding ◽

Osteogenesis Imperfecta ◽

Binding Sites ◽

Collagen Type ◽

Genetic Disorder ◽

Fatal Outcome ◽

Collagen Type I ◽

Type I ◽

Sequencing Analysis ◽

Ligand Binding Sites

Osteogenesis imperfecta (OI) is a rare genetic disorder demonstrating considerable phenotypic and genetic heterogeneity. The extensively studied genotype–phenotype correlation is a crucial issue for a reliable counseling, as the disease is recognized at increasingly earlier stages of life, including prenatal period. Based on population studies, clusters in COL1A1 and COL1A2 genes associated with the presence of glycine substitutions leading to fatal outcome have been distinguished and named as “lethal regions.” Their localization corresponds to the ligand-binding sites responsible for extracellular interactions of collagen molecules, which could explain high mortality associated with mutations mapping to these regions. Although a number of non-lethal cases have been identified from the variants located in lethal clusters, the mortality rate of mutations has not been updated. An next generation sequencing analysis, using a custom gene panel of known and candidate OI genes, was performed on a group of 166 OI patients and revealed seven individuals with a causative mutations located in the lethal regions. Patients’ age, ranging between 3 and 25 years, excluded the expected fatal outcome. The identification of non-lethal cases caused by mutations located in lethal domains prompted us to determine the actual mortality caused by glycine substitutions mapping to lethal clusters and evaluate the distribution of all lethal glycine mutations across collagen type I genes, based on records deposited in the OI Variant Database. Finally, we identified six glycine substitutions located in lethal regions of COL1A1 and COL1A2 genes, of which four are novel. The review of all mutations in the dedicated OI database, revealed 33 distinct glycine substitutions in two lethal domains of COL1A1, 26 of which have been associated with a fatal outcome. Similarly, 109 glycine substitutions have been identified in eight lethal clusters of COL1A2, of which 51 have been associated with a fatal manifestation. An analysis of all glycine substitutions leading to fatal phenotype, showed that their distribution along collagen type I genes is not regular, with 17% (26 out of 154) of mutations reported in COL1A1 and 64% (51 out of 80) in COL1A2 corresponding to localization of the lethal regions.

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Osteogenesis Imperfecta

10.1093/med/9780190678333.003.0061 ◽

2018 ◽

Author(s):

Aimee G. Kakascik

Keyword(s):

Osteogenesis Imperfecta ◽

Genetic Disorder ◽

Bone Fragility ◽

Type I ◽

Multiple Fractures ◽

Systemic Involvement ◽

Collagen Formation ◽

Different Types ◽

Clinical Triad ◽

Blue Sclerae

Osteogenesis imperfecta (OI) is a genetic disorder that affects collagen formation and ultimately leads to increased bone fragility. The fragile nature of the bones leads to fractures, even from seemingly normal patient care. Affected patients are at the highest risk for unintentional fractures during perioperative care. There are several different types of OI. Type I is the most common. With the different types come varying degrees of severity. Types II and III are the more severe forms. The classic clinical triad seen in OI is blue sclerae, multiple fractures, and conductive hearing loss. The patient may have other systemic involvement beyond the fragile musculoskeletal system. It is imperative that the anesthesiologist be well-versed in the natural history and perioperative management of patients with OI in order to optimize care and minimize complications.

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Collagen metabolism in cultured osteoblasts from osteogenesis imperfecta patients

Biochemical Journal ◽

10.1042/bj2860073 ◽

1992 ◽

Vol 286 (1) ◽

pp. 73-77 ◽

Cited By ~ 14

Author(s):

M Mörike ◽

R E Brenner ◽

G B Bushart ◽

W M Teller ◽

U Vetter

Keyword(s):

Osteogenesis Imperfecta ◽

Type I Collagen ◽

Collagen Type ◽

Bone Cells ◽

Collagen Type I ◽

Collagen Metabolism ◽

Type I ◽

Type Iii ◽

Type Iv

Collagen produced in vitro by bone cells isolated from 19 patients with different forms of osteogenesis imperfecta (OI) was analysed. Clinically, four patients were classified as OI type I, 10 patients as OI type III and five patients as OI type IV. Bone cells of 12 of the 19 OI patients produced structurally abnormal type I collagen. Electrophoretically uniformly slower migrating collagen type I alpha-chains were found in one case of OI type I, in seven cases of OI type III and in one case of OI type IV; two cultures of OI type III produced two different populations of collagen type I alpha-chains, and one culture of OI type IV showed reduction-sensitive dimer formation of alpha 1(I) chains, resulting from the inadequate incorporation of a cysteine residue into the triple helical domain of alpha 1(I). Quantitative analysis of collagen metabolism led to the distinction of two groups of cultured OI osteoblasts. In osteoblasts of OI type I, mainly production of collagen was decreased, whereas secretion, processing and pericellular accumulation of (pro)collagen type I was similar to that in control osteoblasts. In contrast, in osteoblasts of OI types III and IV, production as well as secretion, processing and pericellular accumulation of (pro)collagen type I were significantly decreased. Low levels of type I collagen were found irrespective of the presence or absence of structural abnormalities of collagen type I in all OI types.

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Complex spine deformities in young patients with severe osteogenesis imperfecta: current concepts review

Journal of Children s Orthopaedics ◽

10.1302/1863-2548.13.180185 ◽

2019 ◽

Vol 13 (1) ◽

pp. 22-32 ◽

Cited By ~ 4

Author(s):

R. M. Castelein ◽

C. Hasler ◽

I. Helenius ◽

D. Ovadia ◽

M. Yazici ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Young Patients ◽

Surgical Care ◽

Collagen Type I ◽

Bone Fragility ◽

Type I ◽

Vertebral Deformities ◽

Spine Deformities ◽

Paediatric Orthopaedic ◽

Chest Deformities

The severity of osteogenesis imperfecta (OI), the associated reduced quality and quantity of collagen type I, the degree of bone fragility, ligamentous laxity, vertebral fractures and multilevel vertebral deformities all impair the mechanical integrity of the whole spinal architecture and relate to the high prevalence of progressive kyphoscoliotic deformities during growth. Bisphosphonate therapy may at best slow down curve progression but does not seem to lower the prevalence of deformities or the incidence of surgery. Brace treatment is problematic due to pre-existing chest wall deformities, stiffness of the curve and the brittleness of the ribs which limit transfer of corrective forces from the brace shell to the spine. Progressive curves entail loss of balance, chest deformities, pain and compromise of pulmonary function and eventually require surgical stabilization, usually around puberty. Severe vertebral deformities including deformed, small pedicles, highly brittle bones and chest deformities, short deformed trunks and associated issues like C-spine and cranial base abnormalities (basilar impressions, cervical kyphosis) as well as deformed lower and upper extremities are posing multiple peri- and intraoperative challenges. Hence, an early multidisciplinary approach (anaesthetist, pulmonologist, paediatric orthopaedic spine surgeon) is mandatory.This paper was written under the guidance of the Spine Study Group of the European Paediatric Orthopaedic Society. It highlights the most pertinent information given in the current literature and various practical aspects on surgical care of spine deformities in young OI patients based on the personal experience of the contributing authors.

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Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta

Journal of Osteoporosis ◽

10.4061/2011/540178 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 43

Author(s):

I. Mouna Ben Amor ◽

Francis H. Glorieux ◽

Frank Rauch

Keyword(s):

Osteogenesis Imperfecta ◽

Autosomal Dominant ◽

Collagen Type ◽

Collagen Type I ◽

Bone Fragility ◽

Clinical Severity ◽

Type I ◽

Review Of The Literature ◽

Single Centre ◽

Wide Range

Osteogenesis imperfecta, discussed in Baldridge et al. 2008 is an inherited bone fragility disorder with a wide range of clinical severity that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I alpha chains. Here we describe genotype-phenotype correlations in OI patients who have mutations affecting collagen type I. This paper is based on findings in a large single-centre OI population and a review of the literature.

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Hearing Loss in Finnish Adults with Osteogenesis Imperfecta: A Nationwide Survey

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940211101014 ◽

2002 ◽

Vol 111 (10) ◽

pp. 939-946 ◽

Cited By ~ 78

Author(s):

Kaija Kuurila ◽

Reijo Johansson ◽

Ilkka Kaitila ◽

Reidar Grénman

Keyword(s):

Hearing Loss ◽

Osteogenesis Imperfecta ◽

Clinical Features ◽

Genetic Disorder ◽

Nationwide Survey ◽

Bone Fragility ◽

Type I ◽

Impaired Hearing ◽

Hearing Ability ◽

Blue Sclerae

Hearing loss, bone fragility, and blue sclerae are the principal clinical features in osteogenesis imperfecta (OI), a genetic disorder of connective tissue. In a nationwide search, an audiometric evaluation of 133 adult patients was performed. According to the criteria introduced by Sillence, type I was the most common form of OI. Of the patients with normal hearing on audiometry, 17.1% reported subjective hearing loss, and 19.1% of the patients with impaired hearing did not recognize it. On audiometry, 57.9% of the patients had hearing loss, which was progressive, often of mixed type, and mostly bilateral, and began in the second to fourth decades of life. The frequency or severity of the hearing loss was not correlated with any other clinical features of OI. Hearing loss is common, affecting patients with all types of OI. Subjective misjudgment of hearing ability supports the need for repeated audiometry in all OI patients. A baseline study at the age of 10 years followed by audiograms every third year thereafter is recommended.

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Metabolic phenotype in the mouse model of osteogenesis imperfecta

Journal of Endocrinology ◽

10.1530/joe-17-0335 ◽

2017 ◽

Vol 234 (3) ◽

pp. 279-289 ◽

Cited By ~ 7

Author(s):

Iris Boraschi-Diaz ◽

Josephine T Tauer ◽

Omar El-Rifai ◽

Delphine Guillemette ◽

Geneviève Lefebvre ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Collagen Type I ◽

Bone Fragility ◽

Metabolic Phenotype ◽

Whole Body ◽

Type I ◽

Undercarboxylated Osteocalcin ◽

Activity Levels ◽

Body Energy ◽

Circulating Levels

Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2. Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O2 consumption and CO2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin.

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Collagen transport and related pathways in Osteogenesis Imperfecta

Human Genetics ◽

10.1007/s00439-021-02302-2 ◽

2021 ◽

Author(s):

Lauria Claeys ◽

Silvia Storoni ◽

Marelise Eekhoff ◽

Mariet Elting ◽

Lisanne Wisse ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Posttranslational Modifications ◽

Collagen Type ◽

Retrograde Transport ◽

Collagen Type I ◽

Bone Fragility ◽

Disease Classification ◽

Type I ◽

Complex Process ◽

Molecular Landscape

AbstractOsteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classification and disease course prediction. Although collagen type I defects are long established as the primary cause of the bone pathology, we are still far from comprehending the complete mechanism. In the last years, the advent of next generation sequencing has triggered the discovery of many new genetic causes for OI, helping to draw its molecular landscape. It has become clear that, in addition to collagen type I genes, OI can be caused by multiple proteins connected to different parts of collagen biosynthesis. The production of collagen entails a complex process, starting from the production of the collagen Iα1 and collagen Iα2 chains in the endoplasmic reticulum, during and after which procollagen is subjected to a plethora of posttranslational modifications by chaperones. After reaching the Golgi organelle, procollagen is destined to the extracellular matrix where it forms collagen fibrils. Recently discovered mutations in components of the retrograde transport of chaperones highlight its emerging role as critical contributor of OI development. This review offers an overview of collagen regulation in the context of recent gene discoveries, emphasizing the significance of transport disruptions in the OI mechanism. We aim to motivate exploration of skeletal fragility in OI from the perspective of these pathways to identify regulatory points which can hint to therapeutic targets.

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