Popcorn calcification in osteogenesis imperfecta: incidence, progression, and molecular correlation

Abstract

Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe OI have extreme short stature and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII OI, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen mutations associated with popcorn calcifications occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI).

FIG. 1.

Examples of progression of popcorn calcifications over 6–11 years in lower limb radiographs of three patients with osteogenesis imperfecta. Note popcorn development in bilateral distal femora and proximal tibia in patient 3, while popcorn calcification is limited to bilateral distal femora in patients 11 and 12.

FIG. 2.

Leg length discrepancy associated with popcorn calcification in osteogenesis imperfecta. Patient 14 had a 4-year time lag between onset of popcorn calcifications in left and right femur resulting in R > L femur length. Note beginning of popcorn calcification in proximal left tibia. Patient 15 had unilateral onset of popcorn in left femur resulting in R > L femur length.