Osteogenesis imperfecta-pathophysiology and therapeutic options.
| Title: | Osteogenesis imperfecta-pathophysiology and therapeutic options. |
|---|---|
| Authors: | Etich J; Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopedic University Hospital Friedrichsheim gGmbH, Frankfurt/Main, Germany.; Leßmeier L; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Human Genetics, Cologne, Germany.; Rehberg M; Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, Cologne, Germany.; Sill H; Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, Cologne, Germany.; Zaucke F; Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopedic University Hospital Friedrichsheim gGmbH, Frankfurt/Main, Germany.; Netzer C; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Human Genetics, Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Center for rare diseases, University of Cologne, Cologne, Germany.; Semler O; Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, Cologne, Germany. joerg.semler@uk-koeln.de.; Faculty of Medicine and University Hospital Cologne, Center for rare diseases, University of Cologne, Cologne, Germany. joerg.semler@uk-koeln.de. |
| Source: | Molecular and cellular pediatrics [Mol Cell Pediatr] 2020 Aug 14; Vol. 7 (1), pp. 9. Date of Electronic Publication: 2020 Aug 14. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Springer Country of Publication: Germany NLM ID: 101660689 Publication Model: Electronic Cited Medium: Print ISSN: 2194-7791 (Print) Linking ISSN: 21947791 NLM ISO Abbreviation: Mol Cell Pediatr Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Heidelberg : Springer, [2014]- |
| Abstract: | Osteogenesis imperfecta (OI) is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased bone fragility as well as additional, variable extraskeletal symptoms. Here, we present an overview of the genetic heterogeneity and pathophysiological background of OI as well as OI-related bone fragility disorders and highlight current therapeutic options.The most common form of OI is caused by mutations in the two collagen type I genes. Stop mutations usually lead to reduced collagen amount resulting in a mild phenotype, while missense mutations mainly provoke structural alterations in the collagen protein and entail a more severe phenotype. Numerous other causal genes have been identified during the last decade that are involved in collagen biosynthesis, modification and secretion, the differentiation and function of osteoblasts, and the maintenance of bone homeostasis.Management of patients with OI involves medical treatment by bisphosphonates as the most promising therapy to inhibit bone resorption and thereby facilitate bone formation. Surgical treatment ensures pain reduction and healing without an increase of deformities. Timely remobilization and regular strengthening of the muscles by physiotherapy are crucial to improve mobility, prevent muscle wasting and avoid bone resorption caused by immobilization. Identification of the pathomechanism for SERPINF1 mutations led to the development of a tailored mechanism-based therapy using denosumab, and unraveling further pathomechanisms will likely open new avenues for innovative treatment approaches. |
| References: | Nat Commun. 2016 Jul 06;7:11920. (PMID: 27380894); Am J Hum Genet. 2012 Aug 10;91(2):349-57. (PMID: 22863195); Bone. 2002 Jul;31(1):12-8. (PMID: 12110406); J Bone Miner Res. 2018 Jul;33(7):1260-1271. (PMID: 29669177); N Engl J Med. 2010 Feb 11;362(6):521-8. (PMID: 20089953); Am J Hum Genet. 2019 Oct 3;105(4):836-843. (PMID: 31564437); J Bone Miner Res. 2005 May;20(5):758-63. (PMID: 15824848); J Med Genet. 2018 Apr;55(4):278-284. (PMID: 29358272); Am J Hum Genet. 2013 Apr 4;92(4):590-7. (PMID: 23499310); N Engl J Med. 2013 Oct 17;369(16):1529-36. (PMID: 24088043); Am J Hum Genet. 2011 Mar 11;88(3):362-71. (PMID: 21353196); Orphanet J Rare Dis. 2018 Sep 10;13(1):158. (PMID: 30201006); Cochrane Database Syst Rev. 2016 Oct 19;10:CD005088. (PMID: 27760454); Am J Hum Genet. 2010 Jul 9;87(1):110-4. (PMID: 20579626); Am J Hum Genet. 2009 Oct;85(4):521-7. (PMID: 19781681); J Child Orthop. 2019 Feb 1;13(1):12-21. (PMID: 30838071); Am J Med Genet A. 2014 Jun;164A(6):1470-81. (PMID: 24715559); Am J Hum Genet. 2015 Mar 5;96(3):432-9. (PMID: 25683121); Hum Mol Genet. 2018 Dec 15;27(24):4249-4262. (PMID: 30204862); PLoS Genet. 2014 Jun 26;10(6):e1004465. (PMID: 24968150); Am J Hum Genet. 1990 May;46(5):975-82. (PMID: 2339695); Orphanet J Rare Dis. 2014 Sep 26;9:145. (PMID: 25257953); Am J Hum Genet. 2015 Jun 4;96(6):979-85. (PMID: 26027498); Hum Mol Genet. 2015 Apr 1;24(7):1918-28. (PMID: 25510505); Hum Mutat. 2012 Feb;33(2):343-50. (PMID: 22052668); Nat Rev Dis Primers. 2017 Aug 18;3:17052. (PMID: 28820180); Orphanet J Rare Dis. 2013 Sep 30;8:154. (PMID: 24079343); Transl Res. 2017 Mar;181:27-48. (PMID: 27914223) |
| Grant Information: | FOR 2722 Deutsche Forschungsgemeinschaft |
| Contributed Indexing: | Keywords: Bisphosphonates; Genetic heterogeneity; Osteogenesis imperfecta; Pathophysiology; Therapy |
| Entry Date(s): | Date Created: 20200816 Latest Revision: 20210110 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7427672 |
| DOI: | 10.1186/s40348-020-00101-9 |
| PMID: | 32797291 |
| Database: | MEDLINE |
Journal Article; Review