Osteogenesis imperfecta: Type I collagen and skeletal formation

The remarkable technology of molecular biology has led to a major advance in our understanding of the genetic basis of osteogenesis imperfecta (OI). The OI phenotype includes brittle bones with skeletal deformity, blue sclerae, joint laxity, and short stature. Although four clinical groups, OI types I-IV, have been defined, the expression of the OI phenotype is highly variable. Most but not all cases result from mutations in the genes coding for the proalpha 1 or proalpha 2 chains of type I collagen, the main structural protein of skin, tendon, and bone. These mutations result in either structurally defective type I collagen molecules or the production of half-normal amounts of otherwise normal collagen (null allele mutations). An unequivocal relationship between specific mutations and the OI phenotype has not been defined. The possibility remains that certain OI cases may involve mutations affecting other matrix proteins. The growth of OI fibroblasts and osteoblasts in tissue culture is defective, as is extracellular matrix formation including collagen and proteoglycan synthesis by OI osteoblasts. A new murine model of human OI, oim, duplicates the human disease and offers the opportunity for innovative research into the genetics and therapy of this disorder. OI, although an exciting subject for contemporary research, should be considered by the endocrinologist in the differential diagnosis of idiopathic osteoporosis in children and adults.