Anabolic Versus Catabolic Skeletal Effects of Endurance or Resistance Exercise in Older Veterans

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Exercise is frequently recommended to reduce the risk of osteoporotic fracture. However, bone does not always result in the expected improvements in bone mass, and there is evidence that endurance exercise may lead to bone loss under certain conditions. It is our contention that disruptions in calcium homeostasis during exercise, resulting in a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and c-telopeptide of type I collagen (CTX; a marker of bone resorption) that occur shortly after the start of exercise, may be responsible for the lack of the expected improvements in bone mineral density. The iCa, PTH, and CTX responses to exercise have been well-characterized for both young and older adults in response to a single endurance exercise bout, but it is unclear if resistance training (e.g., weightlifting) results in the same exercise-induced disruption in calcium homeostasis. Further, it is unclear how the iCa, PTH, and CTX response to exercise may change with exercise training, and if a bone anabolic response to exercise can be detected after repeat exercise bouts. The bone anabolic response to exercise (assessed by procollagen of type I terminal propeptide, P1NP; a marker of bone formation) has yet to be fully characterized, but that may be due to the testing of single exercise bouts and the short sampling timeline following exercise. To address these gaps in knowledge, up to 60 Veterans (30 men, 30 women), aged 60-80 years, will be randomized to 1) stationary cycling; or 2) resistance training and will complete 10 weeks of supervised exercise training 3x/week (30 total exercise training sessions). This number of exercise visits was due to the demonstrated increase in P1NP after 28 doses of teriparatide, a PTH analog, that results in bone formation. During the 1st, 15th, and 30th exercise training session, participants will undergo an acute exercise testing bout with pre- and post-exercise sampling up to 48 hours after exercise. Blood samples will be collected to measure iCa, PTH, CTX and P1NP. The primary aims are 1) to determine if resistance exercise results in a different bone biomarker response compared to what we have observed during endurance exercise in older adults; 2) determine if resistance and/or endurance exercise result in an increase in P1NP over 10 weeks of exercise training. Exploratory outcomes related to changes in fitness and functional status will address how Veteran health is impacted by each exercise type, which will be used to inform future applications. The biomarker and functional outcomes information are the next step in determining the appropriate “dose” of exercise, consisting of factors such as exercise type, frequency, duration, and intensity (which will be explored in future research), can be used to enhance Veteran health. Exercise should continue to be recommended for overall health, but future interventions could incorporate what is known about the dose of exercise that is needed for cardiometabolic health and the emerging data on the dose of exercise needed to preserve bone health to create personalized exercise prescriptions to improve multiple components of Veteran health. The proposed research is significant because it is investigating several knowledge gaps that need to be addressed to design future, larger exercise and lifestyle interventions aimed at preserving multiple components of Veteran health, which could have a lasting impact on Veteran quality of life and functional independence. The proposed research is innovative because it is testing novel hypotheses, the mode of exercise on the disruption in calcium homeostasis and the role of exercise training, in a population that could greatly benefit from the knowledge to be gained. Long-term, information gleaned from this research will help to define personalized exercise prescriptions to improve cardiometabolic health without compromising bone health in aging Veterans.