Osteogenesis imperfecta (OI) is commonly associated with short stature, but it is unclear whether this is exclusively secondary to fractures and bone deformities or whether there is a primary defect in longitudinal bone growth. As metacarpal and phalangeal bones are rarely affected by fractures and deformities, any length deficits in these bones should reflect a direct disease effect on longitudinal growth. This study therefore assessed the relationship of hand bone length with clinical OI type and genotype.
The length of all 19 tubular hand bones were measured in 144 individuals (age 6 to 57 years; 68 female) who had OI caused by COL1A1 or COL1A2 variants. Measurements of bone length were converted to z-scores using published reference data. Bone length was mostly normal in OI type I but was significantly decreased in OI types III and IV. Mean hand bone length z-score (i.e., the average length z-score of all 19 bones of a hand) was −0.2 for OI type I, −2.9 for OI type III and −1.2 for OI type IV. Mean hand bone length z-score was positively associated with height z-score (r2 = 0.65, P < 0.001). Regarding genotype-phenotype correlations, mean hand bone length z-score was close to 0 in individuals with COL1A1 mutations leading to haploinsufficiency but were significantly lower in the presence of mutations leading to triple-helical glycine substitutions in either the alpha 1 or alpha 2 chain of collagen type I.
COL1A1 and COL1A2 mutations affect bone growth not only by inducing fractures and bone deformities, but also through longitudinal growth deficits in bones that do not fracture or deform.
Investigator, CHEO Research Institute