Treatment of osteogenesis imperfecta with bisphosphonates

Abstract

Osteogenesis imperfecta (OI) is also known as Lobstein syndrome. It is an autosomal dominant genetic dis-order but in the past few years there is evidence of some recessive forms related to mutations in other genes (types 6, 7 and 8). OI is mostly caused by a mutation in the COL1A1 and COL1A2 genes encoding type I collagen. A substitution of the amino acid glycine with a larger amino acid in the structure of collagen leads to defective connective tissue. OI is either inherited or occurs spontaneously. Three alfa chains are the base of the collagen structure. Collagen synthesis includes an altering of each chain by cleavage, hydroxylation, glycosylation and then assembling them into a triple helix structure. In OI, insufficient normal molecules are produced due to defects in the intracellular events forming pro-alpha chains and helices are not formed. The disorder is characterized with brittle bones, muscle weakness, dental and respiratory problems, scoliosis, blue sclera, triangular face, macrocephaly, joint laxity and fractures. There is no cure for OI. However, there are ways to manage the disorder. The aim is to sustain mobility, bone mass, muscle strength and prevent fractures. Treatment may include intake of bisphosphonates, surgery (bone marrow transplantation), physiotherapy and physical aids. Bisphosphonates, growth factor, teripara-tide (a recombinant human form of parathyroid hormone) are directed to improving the function of osteo- blasts and suppressing osteoclasts which helps people with OI live a less painful life.