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Brandon Macias, Ph.D


The estimated lifetime risks of an osteoporotic fracture are about 50% in women and 22% in men. Fractures in the elderly lead to large, often irreversible loss of quality of life and are associated with an increased risk of death. Furthermore, annual direct-care costs attributable to osteoporotic fractures are estimated to cost up to $18 billion in the United States. Most research to date has shown that regular weight bearing exercise helps preserve bone mineral density in postmenopausal women and older men.  

 

Older individuals are not the only ones at risk of bone loss. During spaceflight, astronauts have limited weight-bearing activities and thus are subject to bone loss.  Reduced loading to bone and muscle during spaceflight results in profound reductions in muscle and bone mass.  Reduced loading occurs because in space the gravitational force is minimal and therefore muscles to not have to work against gravity to stand up or to walking as people do on Earth. Astronauts on International Space Station (ISS) expeditions show a monthly rate of bone loss of 1.4-1.5% at the hip and 0.9% at the spine.  This rate of bone loss observed during on ISS missions is 10-fold higher than that of a postmenopausal woman.

 

It is well established that the loading to bone that occurs with exercise is actually a potent bone forming stimulus.  However, it is unclear how bone cells sense those forces during exercise.

 

Recent research has demonstrated that Wnt signaling in bone cells plays a pivotal role in directing bone cell activity.  In fact, compelling data suggest that wnt signaling in bone cells is responsible for sensing those exercise-induced forces. Therefore, understanding how bone cells use the Wnt signaling pathway to increase bone mass will aid in the development of new therapeutic strategies that may help prevent osteoporotic fractures.

 

Simulated resistance exercise performed in an animal model similar to a leg press exercise performed by humans prevents bone loss.  For example, simulated resistance exercise performed three times per week prevented the usual non-weight-bearing bone loss observed when no exercise was performed.  Moreover, current research has documented that Wnt signaling rises with exercise but drops during sedentary periods. Therefore, the Wnt pathway may be the primary way that bone cells “talk” to each other and direct bone gain and loss.  Determining how Wnt signaling is regulated during simulated spaceflight conditions with resistance exercise will aid in the development of bone loss countermeasures for clinical medicine and for astronauts.

           

                                                  

Further reading:

  1. BR Macias, JM Swift, MI Nilsson, HA Hogan, SD Bouse, and SA Bloomfield.  Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse. Journal of Applied Physiology, 112(5): 918-25, 2012. http://jap.physiology.org/content/jap/112/5/918.full.pdf
  2. JM Swift, SN Swift, MI Nilsson, HA Hogan, SD Bouse, and SA Bloomfield.  Cancellous bone formation responses to simulated resistance training during disuse is blunted by concurrent alendronate treatment.  J Bone Mineral Research, 26: 2140-2150, 2011. http://onlinelibrary.wiley.com/doi/10.1002/jbmr.407/pdf
  3. Robling AG, Castillo AB, and Turner CH. Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455-98, 2006. http://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.8.061505.095721
  • Where “Wnt” The Bone!  Resistance Exercise Prevents Bone Loss


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