Sclerostin Response to Exercise: Association with Bone Turnover, Oxidative Stress and Inflammation

Abstract

The purpose of this thesis was to compare the response of sclerostin, a bone-specific glycoprotein that downregulates bone formation, to two modes (high impact vs non-impact) of high intensity interval exercise and to examine its relationship to potential exercise-induced changes in bone turnover (Study 1), oxidative stress (Study 2) and inflammation (Study 3). For the three studies included in this thesis, 40 healthy, young (18-25 years old) female and male adults performed two high intensity interval exercise trials in random order. Trials consisted of eight repetitions of 1 min high intensity running or cycling (mean heart rate 90% of maximum), separated by 1 min passive recovery intervals between repetitions. Blood samples were collected pre-exercise, and 5 min, 1h, 24h and 48h post-exercise. Sclerostin, bone turnover markers (cross linked telopeptide of type Ⅰ collagen [CTXI], procollagen type I amino-terminal propeptide [PINP]), oxidative stress markers (thiobarbituric acid reactive substances [TBARS], protein carbonyls [PC]) and inflammatory cytokines (interleukin-1β [IL-1β], -10 [IL-10], -6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) were measured in serum. In the first two studies, sclerostin showed a significant time effect, but no significant exercise mode effect or interaction in both females (study 1) and males (study 2). In study 3, sclerostin showed a significant main effect for sex and a significant sex-by-time interaction. Specifically, sclerostin significantly increased from pre- to 5 min post-exercise and returned to baseline levels within 1h post-exercise with greater increase in males than females (47% vs. 34%, respectively). Furthermore, there were no correlations between sclerostin’s exercise-induced increase and the corresponding changes in bone turnover and oxidative stress markers. In contrast, sclerostin’s increase 5 min post-exercise was significantly correlated with the corresponding increase in the inflammatory cytokines, especially TNF-α, which along with sex, significantly explained 34% of the variance in its post-exercise elevation. In conclusion, in both young females and males, one session of high intensity interval exercise leads to an increase in sclerostin immediately post-exercise, and this increase is of similar magnitude following high impact and no impact exercise. Furthermore, the increase in sclerostin 5 min post-exercise seems to be associated with the exercise-induced inflammation.