| Abstract: | A positive family history is considered a risk factor for osteoporosis (OP) although the genetic or biochemical basis for this relationship remains undefined. Various mutations affecting normal synthesis of type I collagen have been reported in osteogenesis imperfecta (OI), a heritable disorder of connective tissue. Family A, in which the proband and a daughter are afflicted with OP and idiopathic scoliosis was examined for defects in collagen metabolism. Dermal fibroblast cultures were established to investigate de novo collagen synthesis. SDS-PAGE revealed an abnormally migrating alpha 2(I) chain and procollagen in two generations. Examination of the kinetics of type I collagen pC & N-propeptide processing demonstrated a rate 2x control in the proband. The phenotype family A is not OI. It shares features with families B & C, having familial clustering of OP. However, collagen synthesis was not abnormal in family B & C. These data suggest that in family A the alpha 2(I) structural defect may be related to defective skeletal matrix formation. |
