Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes

Excessive exercise can have detrimental effects on bone; however, the mechanisms leading to bone loss are not well understood. Sclerostin and preadipocyte factor (Pref)-1 are two hormones which inhibit bone formation. The present study demonstrates that these hormones may have differential effects in athletes as compared to non-athletes. Exercise activity is common in female adolescents, however, excessive exercise can have detrimental effects on bone mineral density (BMD). Mechanisms underlying this decrease in bone mass are not well understood. We investigated the effects of sclerostin, a potent inhibitor of bone formation via WNT signaling inhibition, and Pref-1, a suppressor of osteoblast differentiation, on BMD, bone turnover markers and bone strength in adolescent athletes. We studied 50 adolescents between 15-21 years of age: 17 amenorrheic athletes (AA), 17 eumenorrheic athletes (EA), and 16 nonathletic controls (NA). We measured spine and hip BMD by dual energy x-ray absorptiometry and estimated failure load and stiffness at the distal radius and tibia using micro-finite element analysis. We also measured fasting sclerostin, Pref-1, N-terminal propeptide of type 1 procollagen, and C-terminal collagen cross-links levels. Sclerostin levels were higher in AA and EA compared with NA (AA: 0.42 +/- 0.15 ng/mL, EA: 0.44 +/- 0.09 ng/mL, NA: 0.33 +/- 0.14 ng/mL; p = 0.047). In EA, sclerostin was positively associated with lumbar spine (LS) BMD and its Z-score (R = 0.52, p = 0.03 and R = 0.55, p = 0.02, respectively) whereas in NA, sclerostin was inversely associated with LS BMD (R = -0.61, p = 0.01). Pref-1 levels were similar in all three groups and there were significant inverse associations between Pref-1, BMD, and estimated bone strength in NA. Sclerostin and Pref-1 may have differential effects on bone in adolescent athletes compared to non-athletes.