Impact of Exercise on Biomechanical Integrity and Molecular Structural Properties of Bone

Investigators: Charlotte L Phillips, UMC-Biochemistry; Yong Wang, UMKC-Dentistry (Co-PIs)
Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by small stature, reduced bone mineral density, and frequent fractures. OI most often results from mutations in either of the type I collagen genes, COL1A1 and COL1A2. Bone is inherently mechanosensitive, responding and adapting to its mechanical environment. Bone formation occurs in response to high mechanical loads; often changing its geometry to strengthen the skeleton. The largest physiological loads bones typically experience are from muscles, and bone strength is directly proportional to muscle mass. In humans, during the normal 2 year prepubertal/pubertal growth period normal children attain 26% of their peak bone mass, and children which are physically active accrue 10-40% more bone (region specific) than inactive children. This suggests that sedentary lifestyle choices for OI children are particularly detrimental to their bone health. We postulate that even though the OI bone material is biomechanically weaker, the bone will respond to muscle loading, especially during pubertal growth; by altering bone geometry, architecture, and/or mass to generate an inherently stronger bone. We propose to utilize the oim mouse to determine if weight bearing and/or non weight bearing exercise will increase oim muscle mass and concomitantly improve bone biomechanical integrity, and to investigate the molecular, biochemical, structural and biomechanical impact of exercise on OI bone at the macro-, ultra- and nano-structural levels. The potential benefits of therapeutic exercise to OI patients are significant.