scholarly journals THERAPY OF ENDOCRINE DISEASE: Treatment of osteogenesis imperfecta in adults

2014 ◽  
Vol 171 (2) ◽  
pp. R79-R90 ◽  
Author(s):  
Katarina Lindahl ◽  
Bente Langdahl ◽  
Östen Ljunggren ◽  
Andreas Kindmark
Keyword(s):  
Osteogenesis Imperfecta ◽  
Pharmacological Treatment ◽  
Treatment Options ◽  
Collagen Type I ◽  
Connective Tissue Disorder ◽  
Current Evidence ◽  
Type I ◽  
Duration Of Treatment ◽  
Weak Support ◽  
Medical Needs

BackgroundOsteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type I genes. Pharmacological treatment has been most extensively studied in children, and there are only few studies comprising adult OI patients.Objectivesi) To review the literature on the current medical management of OI in children and adults, and thereby identify unmet medical needs and ii) to present an overview of possible future treatment options.ResultsIndividualization and optimization of OI treatment in adults remain a challenge, because available treatments do not target the underlying collagen defect, and available literature gives weak support for treatment decisions for adult patients.ConclusionsBisphosphonates are still the most widely used pharmacological treatment for adult OI, but the current evidence supporting this is sparse and investigations on indications for choice and duration of treatment are needed.

scholarly journals Compound phenotype of osteogenesis imperfecta and Ehlers–Danlos syndrome caused by combined mutations in COL1A1 and COL5A1

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Zejia Lin ◽  
Jican Zeng ◽  
Xinjia Wang
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type ◽  
Collagen Type I ◽  
Connective Tissue Disorder ◽  
Type I ◽  
Ehlers Danlos Syndrome ◽  
Pathogenic Mutations ◽  
Whole Exome ◽  
Type V ◽  
Danlos Syndrome

Abstract Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with a broad clinical spectrum that can overlap with Ehlers–Danlos syndrome (EDS). To date, patients with both OI and EDS have rarely been reported. In the present study, we investigated a family with four members, one healthy individual, one displaying OI only, and two displaying the compound phenotype of OI and EDS, and identified the pathogenic mutations. Whole exome sequencing was applied to the proband and her brother. To verify that the mutations were responsible for the pathogenesis, conventional Sanger sequencing was performed for all members of the family. We identified a known COL1A1 (encoding collagen type I α 1 chain) mutation (c.2010delT, p.Gly671Alafs*95) in all three patients (the proband, her brother, and her mother) in this family, but also a novel heterozygous COL5A1 (encoding collagen type V α 1 chain) mutation (c.5335A>G, p.N1779D) in the region encoding the C-terminal propeptide domain in the proband and her mother, who both had the compound phenotype of OI and EDS. The results of the present study suggested that the proband and her mother presented with the compound OI–EDS phenotype caused by pathogenic mutations in COL5A1 and COL1A1.

scholarly journals Lumbar Scheuermann’s disease found in a patient with osteogenesis imperfecta (OI) caused by a heterozygous mutation in COL1A2 (c.4048G > A): a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shiwei Wang ◽  
Xiaoli Wang ◽  
Xiaochun Teng ◽  
Songbai Li ◽  
Hanyi Zhang ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Thoracolumbar Spine ◽  
Collagen Type I ◽  
Connective Tissue Disorder ◽  
Heterozygous Mutation ◽  
Type I ◽  
Scheuermann’S Disease ◽  
Scheuermann's Disease ◽  
Schmorl’S Nodes

Abstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann’s disease is an atypical type of Scheuermann’s disease accompanied by Schmorl’s nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann’s disease is unclear, genetic and environmental factors are likely. Case presentation Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl’s nodes. Conclusions This is the first reported case of OI coexisting with the spinal presentation of Scheuermann’s disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann’s disease. In conclusion, this case demonstrates the relationship between Scheuermann’s disease and OI for the first time and enriches the genotype-phenotype spectrum of OI.

Is otosclerosis a generalized connective tissue disorder?

1987 ◽  
Vol 101 (4) ◽  
pp. 307-311 ◽  
Author(s):  
H. Oxlund ◽  
U. Pedersen ◽  
C. C. Danielsen ◽  
I. Oxlund ◽  
O. Elbrønd
Keyword(s):  
Connective Tissue ◽  
Collagen Type ◽  
Collagen Type I ◽  
Connective Tissue Disorder ◽  
Biochemical Properties ◽  
Skin Thickness ◽  
Type I ◽  
Molecular Stability ◽  
Cross Links ◽  
Skin Biopsies

AbstractIt has been suggested that otosclerosis might be caused by a generalized disorder in the connective tissue.The biophysical and biochemical properties of skin biopsies from twelve patients with otosclerosis and twelve age- and sex-matched controls were investigated. No differences were found in skin strength and extensibility, skin thickness, collagen content, the relationship between collagen type I and type III, reducible collagen cross-links and molecular stability of collagen type I of samples from patients with otosclerosis as compared with those from the controls. The present study does not support the suggestion that otosclerosis might be a generalized connective tissue disorder.

scholarly journals Collagen Type I Alpha 1 Mutation Causes Osteogenesis Imperfecta from Mild to Perinatal Death in a Chinese Family

2016 ◽  
Vol 129 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Hong-Yan Liu ◽  
Jia Huang ◽  
Dong Wu ◽  
Tao Li ◽  
Liang-Jie Guo ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type ◽  
Perinatal Death ◽  
Collagen Type I ◽  
Chinese Family ◽  
Type I

scholarly journals Osteogenesis imperfecta: potential therapeutic approaches

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5464 ◽  
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.

scholarly journals Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

2018 ◽  
Vol 65 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Aleksandra Augusciak-Duma ◽  
Joanna Witecka ◽  
Aleksander L. Sieroń ◽  
Magdalena Janeczko ◽  
Jacek J Pietrzyk ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type ◽  
Collagen Type I ◽  
Base Substitution ◽  
Type I ◽  
Intracellular Accumulation ◽  
Single Base ◽  
Type Iii ◽  
Procollagen Type ◽  
Procollagen Type I

Over 85% of osteogenesis imperfecta (OI) cases associates to mutations in procollagen type I genes (COL1A1 or COL1A2), however, no hot spots were linked to particular clinical phenotypes. The 8 patients whom were clinically diagnosed with OI are from Polish population with no ethnic background indicated. Six unpublished mutations were detected in eight patients diagnosed with OI. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were also determined. In COL1A1 gene the mutations were found in exons 2, 22, 50 and in introns 13 and 51. In COL1A2 one mutation was identified in exon 22. Mutations of deletion type in COL1A1 that resulted in OI type I an effect neither on collagen type I secretion nor its intracellular accumulation were detected. Also, a single base substitution in I13 (c.904-9 G>T) was associated with OI type I. The OI type III was associated with single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly®Cys in the central part of triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation to procollagen type I. The results shall help in genetic counseling of OI patients and provide rational support in making by them and their families conscious, life important decisions.

scholarly journals Alendronate for the Treatment of Pediatric Osteogenesis Imperfecta: A Randomized Placebo-Controlled Study

2011 ◽  
Vol 96 (2) ◽  
pp. 355-364 ◽  
Author(s):  
L. M. Ward ◽  
F. Rauch ◽  
M. P. Whyte ◽  
J. D'Astous ◽  
P. E. Gates ◽  
...  
Keyword(s):  
Physical Activity ◽  
Osteogenesis Imperfecta ◽  
Bone Pain ◽  
Collagen Type ◽  
Collagen Type I ◽  
Fracture Incidence ◽  
Controlled Study ◽  
Type I ◽  
Z Score ◽  
Cortical Width

abstract Context: Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta (OI) is limited. Objective: The objective of the investigation was to study the efficacy and safety of daily oral alendronate (ALN) in children with OI. Design and Participants: We conducted a multicenter, double-blind, randomized, placebo-controlled study. One hundred thirty-nine children (aged 4–19 yr) with type I, III, or IV OI were randomized to either placebo (n = 30) or ALN (n = 109) for 2 yr. ALN doses were 5 mg/d in children less than 40 kg and 10 mg/d for those 40 kg and greater. Main Outcome Measures: Spine areal bone mineral density (BMD) z-score, urinary N-telopeptide of collagen type I, extremity fracture incidence, vertebral area, iliac cortical width, bone pain, physical activity, and safety parameters were measured. Results: ALN increased spine areal BMD by 51% vs. a 12% increase with placebo (P < 0.001); the mean spine areal BMD z-score increased significantly from −4.6 to −3.3 (P < 0.001) with ALN, whereas the change in the placebo group (from −4.6 to −4.5) was insignificant. Urinary N-telopeptide of collagen type I decreased by 62% in the ALN-treated group, compared with 32% with placebo (P < 0.001). Long-bone fracture incidence, average midline vertebral height, iliac cortical width, bone pain, and physical activity were similar between groups. The incidences of clinical and laboratory adverse experiences were also similar between the treatment and placebo groups. Conclusions: Oral ALN for 2 yr in pediatric patients with OI significantly decreased bone turnover and increased spine areal BMD but was not associated with improved fracture outcomes.

scholarly journals Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children

2021 ◽  
Vol 9 (5) ◽  
pp. 49
Author(s):  
Huong Thi Thu Nguyen ◽  
Dung Chi Vu ◽  
Duc Minh Nguyen ◽  
Quang Dinh Dang ◽  
Van Khanh Tran ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Disorder ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Open Bite ◽  
Type I ◽  
Dentinogenesis Imperfecta ◽  
Type Iv ◽  
Brown Discoloration ◽  
Study Participants

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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