Physical Activity in Relation to Serum Sclerostin, Insulin-Like Growth Factor-1, and Bone Turnover Markers in Healthy Premenopausal Women: A Cross-Sectional and a Longitudinal Study

Context: There is limited information on the effects of mechanical loading caused by physical activity (PA) on sclerostin, IGF-I, and bone turnover markers (BTM). Objective: The objective of the investigation was to study the relationships between serum sclerostin, serum-IGF-I (s-IGF-I), BTM, and the PA level in premenopausal women and to discern how 8-wk of PA training (PAT) affects the serum levels of sclerostin, IGF-I, and BTM. Design: This was a cross-sectional study with a subgroup followed up longitudinally. Settings and Subjects: A total of 1235 randomly selected premenopausal women were cross-sectionally studied. We also followed up 58 of these women longitudinally during an 8-wk course of PAT (4 d/wk) and compared them with 62 controls. All women were medically examined, and bone mineral density (BMD) and serum levels of sclerostin, s-IGF-I, and BTM were determined. Results: Women with PA of greater than 120 min/wk showed significantly lower serum sclerostin (by 36.8%) but higher s-IGF-I (by 107%) levels than sedentary controls. Bone formation markers were also higher in the PA greater than 120 min/wk group compared with the sedentary controls. In the longitudinal study, the 8-wk PAT program led to a decrease in serum sclerostin (by 33.9%, P < 0.0001) but increases in the serum levels of the bone-formation markers and IGF-I (s-IGF-I by 74.2%, P < 0.0001). Conclusions: This study demonstrates that even minor changes in PA are associated with effects on serum levels of sclerostin, IGF-I, and BTM and suggests that sclerostin could be a link between mechanical loading and disuse osteoporosis in humans. (J Clin Endocrinol Metab 97: 3691-3699, 2012)