Osteogenesis imperfecta: Bench to bedside

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• 作者：Jay R. Shapiro ; MD ; Emily L. Germain-Lee ; MD
• 刊名：Seminars in Arthritis and Rheumatism
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：42
• 期：5
• 页码：547
• 全文大小：49 K

文摘

The Bench

There has been a significant expansion in our understanding of the molecular biology of OI. The number of genes responsible for the disorder has increased from 2 (COL1A1 and COL1A2) in 2007, to 9 in 2012 (CRTAP, LEPRE1, PPIB, Hsp47/SERPINH1, SERPINF1, FKBP10 and most recently, adding IFITM5). Also, there has been additional categorization of clinical OI types since Sillence first recognized 4 OI types in 1978. An issue is the nosology of OI: should that be based on each mutation or should a broad clinical classification be retained? Although multiple mutations have been defined, we have not progressed in our understanding of how each mutation translates to disordered bone and connective-tissue cell function. Although mutations alter osteoblast type I collagen synthesis, the effects on osteoblast cell biology, for example on cell growth, are undefined. The question of genotype/phenotype relationships is exemplified by the wide clinical variability seen in the phenotypic of OI type V where there is apparent consistency in expression of the mutation IFITM5, (genotype) among affected kindreds, more so than occurs in other OI types where multiple mutations are expressed in a particular OI phenotype.

The Bedside

Two clinical issues which are interrelated are: (a) Understanding the pain syndrome in OI, and (b) the status of fracture prevention treatment for children and adults: this includes considerable variability among centers in drug selection (pamidronate vs. zoledronic acid), drug doses which vary from 4 to 9 mg/kg/year in children, and treatment schedules which vary from 4 to 6 months, particularly in children who have already had several years of treatment.