Grant: Discovery Grants Program - Individual

Our understanding of the mechanisms that drive bone mineral acquisition in humans is still limited. Although we, and others, have shown that bone is particularly responsive to exercise during growth, and that overtraining is linked to impaired bone integrity, the threshold at which beneficial physical activity progresses to excessive exercise, with respect to bone, is poorly understood. The long-term objective of our research program is to examine the effects of different type, intensity and duration of exercise on the time course and mechanism(s) involved in the development and adaptive response(s) of bone in children, adolescents and young adults. We hypothesize that: a) there is an age/maturity and sex dependent, optimal range of exercise intensities and durations, and as well level of dietary (energy) intake, that favor the balance between bone formation and bone resorption leading to positive bone adaptation, and b) there is an osteogenic exercise threshold at which excessive exercise tips the balance in favor of bone resorption leading to negative bone adaptation, and which is dependent on sex and skeletal maturity and influenced by dietary energy availability. We will monitor the bone response by means of biochemical (blood) markers that reflect changes in metabolic status of bone, allowing the investigation of the acute effects of exercise on bone. Of particular interest are non-traditional markers of bone turnover including sclerostin, and the ratio of osteoprotegerin (OPG) and receptor activator of nuclear factor ?B ligand (RANKL). *The methodology includes a series of human studies carried out in two phases. The first phase is a series of exercise trials that will examine differences in the acute biochemical responses of bone turnover to various exercise protocols (low vs. high impact) in children, adolescents and young adults of both sexes. Blood samples will be collected prior to exercise, 5 minutes, 1 hour, and 24 hours post-exercise as previously done in our lab, and they will be analyzed for bone formation and resorption markers, including sclerostin and OPG/RANKL, and additional systemic hormonal and inflammatory factors. The second phase includes a series of exercise trials that will examine changes in markers of bone turnover, with focus on sclerostin and OPG/RANKL ratio, in response to moderate versus excessive exercise (high and low impact), in boys and girls, young men and women. We will manipulate the dietary intake (caloric restriction versus regular diet) in young men and women in order to potentially determine if and how dietary intake affects the osteogenic threshold during excessive exercise. This research will offer new evidence about the behavior of the developing bone under stress conditions, and the existence of an osteogenic exercise threshold.