The relationship between circulating hormone levels, bone turnover markers and skeletal development in healthy boys differs according to maturation stage

Introduction: This study investigates peri-pubertal changes in bone turnover markers, Wnt-signalling markers, insulin-like growth factor-1 (IGF-1) and sex steroid levels, and how they reflect skeletal development in peri-pubertal boys. Materials and methods: Population-based study in 118 peri-pubertal boys from the NINIOS cohort (age range at baseline 5.1-17.3 years) with repeated measurements at baseline and after two years. Serum levels of the classical bone turnover markers (BTM) procollagen type 1 N-terminal propeptide and carboxy-terminal collagen crosslinks, as well as sex-hormone binding globulin, IGF-1, osteopmtegerin, sclerostin and dickkopf-1 were measured using immunoassays. Sex steroids (estradiol, testosterone, and androstenedione) were measured using mass spectrometry and free fractions calculated. Dual energy x-ray absorptiometry was used for bone measurements at the lumbar spine and whole body. Volumetric bone parameters and bone geometry at the proximal and distal radius were assessed by peripheral QCT. Pubertal development was categorized based on Tanner staging. Results: During puberty, sex steroid and IGF-1-levels along with most parameters of bone mass and bone size increased every next Tanner stage. In contrast, classical bone turnover markers and sclerostin peaked around mid-puberty, with subsequent declines towards adult values in late puberty. Especially classical BTM and sex steroid levels showed consistent associations with areal and volumetric bone parameters and bone geometry. However, observed associations differed markedly according to pubertal stage and skeletal site. Conclusion: Serum levels of sex steroids, IGF-1 and bone metabolism markers reflect skeletal development in peri-pubertal boys. However, skeletal development during puberty is nonlinear, and the relations between skeletal indices and hormonal parameters are nonlinear as well, and dependent on the respective maturation stage and skeletal site.