Introduction

Osteogenesis imperfecta (OI) is an autosomal dominant genetic disorder of connective tissues, which is also known as ''brittle bone disease'' because of the susceptibility of the affected individuals to fracture from the mildest trauma. It exhibits a broad range of clinical severity, ranging from multiple fracturing and perinatal death to a mild form that may elude clinical detection. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in the either the COL1A1 or COL1A2 gene that encodes the chains of type I procollagen—the major structural protein of bone. The relationship of specific mutations to severity is an exceedingly difficult task. Most patients with mild type I OI produce structurally normal collagen in reduced amounts because of null COL1A1 allele. The structural mutations in patients with types II, III, and IV affect connective tissues through a dominant negative mechanism, in which the presence of the mutant chain results in defective extracellular matrix. Prenatal diagnostic techniques have allowed the early detection of this disorder, particularly in families in which the molecular defect is already known. Because OI is an incurable genetic disease, two alternative approaches for gene therapy are being investigated: one is replacement of mutant cells with normal cells through bone marrow transplantation, and the second involves the suppression of mutant genes by introducing ribozymes into the cells to change a structural defect in collagen to a quantitative defect in normal collagen with mild phenotype. Types V, VI, and VII are not associated with type I collagen gene defects. However, for now, treatment of patients by bisphosphonate therapy can improve bone mass and improve quality of life in all types of OI.

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Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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