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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, osteoprotegerin, 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context: Male-to-female (M-->F) transsexual persons undergo extreme changes in gonadal hormone concentrations, both by pharmacological and surgical interventions. Given the importance of sex steroids for developing and maintaining bone mass, bone health is a matter of concern in daily management of these patients., Objective: To provide data on bone metabolism, geometry and volumetric bone mineral density in M-->F transsexual persons., Design/setting/participants: Twenty-three M-->F transsexual persons, recruited from our gender dysphoria clinic and at least 3 yrs after sex reassignment surgery, together with 46 healthy age- and height-matched control men were included in this cross-sectional study., Main Outcome Measures: Body composition, areal and volumetric bone parameters determined using DXA and peripheral quantitative computed tomography. Hormone levels and markers of bone metabolism assessed using immunoassays. Peak torque of biceps and quadriceps muscles and grip strength assessed using an isokinetic and hand dynamometer, respectively., Results: M-->F transsexual persons presented lower total and regional muscle mass and lower muscle strength as compared to controls (all P<0.001). In addition, they had higher total and regional fat mass (P<0.010) and a lower level of sports-related activity index (P<0.010). Bone mineral content and areal density (aBMD) of the lumbar spine, total hip and distal radius, as well as trabecular vBMD of the distal radius was lower as compared to controls (P<0.010). At cortical sites, no differences in cortical vBMD were observed, whereas M-->F transsexual persons were characterized by smaller cortical bone size at both the radius and tibia (P<0.010). Lower levels of biochemical markers of bone formation and resorption (P<0.010) suggested decreased bone turnover., Conclusion: M-->F transsexual persons have less lean mass and muscle strength, and higher fat mass. In addition, they present lower trabecular vBMD and aBMD at the lumbar spine, total hip and distal radius, and smaller cortical bone size as compared to matched controls. Both the lower level of sports-related physical activity as well testosterone deprivation could contribute to these findings. These results indicate that bone health should be a parameter of interest in the long-term follow-up care for M-->F transsexual persons.

The vitamin D binding protein (DBP) is the major carrier protein for vitamin D metabolites in plasma. Polymorphisms in DBP have been described to be associated with an increased bone fracture risk and diabetes. The present study investigates the influence of both phenotypic and (TAAA)(n)-Alu repeat DBP-polymorphism and DBP-concentration on bone mineral density, body composition, bone turnover- and metabolic markers in a cohort of ambulatory elderly men. We included 211 men (>70 years) in this study. Bone mineral density (BMD) was determined by dual energy X-ray absorptiometry. Bone turnover was assessed by measurement of serum osteocalcin, serum and urinary C-terminal telopeptides of type I collagen and urinary deoxypyridinoline, together with 25(OH)-vitamin D and 1,25(OH)(2)-vitamin D concentrations. DBP-phenotypes were determined electrophoretically and the (TAAA)(n)-Alu repeat polymorphism was determined by polymerase chain reaction. Body composition was estimated using bioelectrical impedance analysis, together with handgrip and arm strength, fasting serum glucose and leptin concentrations. No differences in BMD or bone turnover markers among DBP-phenotypes or (TAAA)(n)-genotypes were observed in this study. Serum 25(OH)-vitamin D was comparable among DBP-variants and did not relate to DBP-concentrations, whereas 1,25(OH)(2)-vitamin D was different among DBP-phenotypes and was correlated positively with DBP-concentrations. DBP-concentrations related positively to body mass index, fat mass, leptin and glucose concentration. The correlation with leptin remained significant after correction for fat mass. Fasting glucose concentrations were different among DBP-phenotypes, whereas no difference was observed between (TAAA)(n)-genotypes. In conclusion, serum 1,25(OH)(2)-vitamin D concentrations are codetermined by DBP-phenotypes and DBP-concentrations. No major effect of DBP-polymorphism was demonstrated on BMD, bone turnover markers or body composition.