Osteoporosis and familial idiopathic scoliosis: association with an abnormal alpha 2(I) collagen.
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.
Shapiro
J R
JR
Bone Metabolism Research Laboratory, Saint Vincent Hospital, Worcester MA 01604.
Burn
V E
VE
Chipman
S D
SD
Velis
K P
KP
Bansal
M
M
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000235:genetics; D010024:Osteoporosis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D010375:Pedigree; D010641:Phenotype; D012600:Scoliosis / Q000150:complications / Q000235:genetics / Q000378:metabolism*
D003094:Collagen