Osteogenesis Imperfecta

Abstract

Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

Soluble activin receptor type IIB decoy receptor differentially impacts murine osteogenesis imperfecta muscle function

“…reported that muscle atrophy in mice due to surgical denervation was not protected by soluble ActRIIB treatment, suggesting increased muscle mass and force via myostatin inhibition may not be effective when there is deterioration of the neuromuscular junction . Muscle atrophy and/or weakness in OI has generally been attributed to immobilization, secondary impacts of neurological impairment or orthopedic casting, and prolonged bed rest due to fractures …”

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

“…To correct for bowing of the long bones, intramedullary rods are inserted in the bone marrow canal to enhance stability and bone alignment [51,52]. Risk of scoliosis in children with the mildest form of OI is 10-fold greater than in the general population [9] and more common even in OI types III and IV [53]. Progression of scoliosis can lead to pulmonary insufficiency [53,54].…”

“…Risk of scoliosis in children with the mildest form of OI is 10-fold greater than in the general population [9] and more common even in OI types III and IV [53]. Progression of scoliosis can lead to pulmonary insufficiency [53,54]. For best results, corrective surgery through spinal fusion should be sought when curvature is below 60° [53].…”

Osteogenesis Imperfecta Type I-IV, the Collagenous Disorder of Connective Tissue in Czech Population

“…Based on clinical signs the first OI classification from David Sillence (created in 1979) distinguished four types of the disease (I-IV). In the past, related to the development methods of analysis, such as molecular-genetic techniques and histological findings, new forms were identified in the IV group of OI -OI type V-IX [13]. The disease exhibits a wide spectrum of clinical and radiological signs and varies in severity from mild to perinatal lethal forms.…”

“…It is composed of two alpha1(I) chains (encoded by COL1A1 gene) and one al-pha2(I) chain (encoded by COL1A2 gene). The mutations of these two genes have the result in decreased production of the protein or in synthesis of structurally defective collagen molecules [13].…”