Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. (19th August 2013)

• Record Type: Journal Article
• Authors: Ben Amor, I Mouna; Roughley, Peter; Glorieux, Francis H; Rauch, Frank
• Is Part Of: Journal of bone and mineral research. Volume 28:Number 9(2013:Sep.)
• Page Start: 2001
• Page End: 2007
• Publication Date: 2013-08-19
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.1942
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jbmr1942-sec-0001" sec-type="section"> <p> <italic>COL1A1</italic> haploinsufficiency mutations lead to the mildest form of osteogenesis imperfecta (OI), OI type I. The skeletal clinical characteristics resulting from such mutations have not been characterized in detail. In this study we assessed 86 patients (36 male, 50 female; mean age 13.3 years; range, 0.6 to 54 years) with <italic>COL1A1</italic> haploinsufficiency mutations, of whom 70 were aged 21 years or less ("pediatric" patients). Birth history was positive for fracture or long‐bone deformity in 12% of patients. The average rate of long‐bone fracture (femur, tibia/fibula, humerus, radius/ulna) in pediatric patients was 0.62 fractures per year, one‐half of which affected the tibia/fibula. Long‐bone fracture rate was negatively associated with age and lumbar spine areal bone mineral density. Vertebral compression fractures were observed in 71% of the 58 pediatric patients who had lateral spine radiographs. The median number of vertebral fractures was higher for females (median 4; range, 0 to 14) than for males (median 1; range, 0 to 8) (<italic>p</italic> = 0.03). Lumbar spine areal bone mineral density was negatively associated with the severity of vertebral compression fractures, as reflected in the spine deformity index. Scoliosis was present in about 30% of pediatric patients but the Cobb angle was <30 degrees in all cases. The average final height <italic>Z</italic>‐score was –1.1, representing a deficit of 8 to 10 cm compared to the general population. In summary, OI patients with <italic>COL1A1</italic> haploinsufficiency mutations have high rates of significant skeletal involvement. Systematic follow‐up of growing patients with <italic>COL1A1</italic> haploinsufficiency mutations including radiographic screening for vertebral compression fractures and scoliosis is warranted.</p> </sec> </abstract>