The data support the view that between-subject variability in serum FT in healthy men is underlain in part by differences in androgen sensitivity and feedback set point, with a contributory role of AR polymorphism. These findings have potential implications for the interpretation of epidemiological studies, diagnosis of hypogonadism, and pharmacogenetics of androgen treatment in men.

Increased fat mass is associated with smaller bone size, challenging the view of a high bone mass index as a protective factor for osteoporosis, whereas lean mass was a consistent positive determinant of bone size.

This study investigates determinants of peak bone mass (PBM) in healthy men, focusing on effects and interactions of parameters reflecting mechanical loading and sex steroids. Healthy male siblings (n = 677; 25-45 yr) were recruited in a cross-sectional, population-based study. Physical activity score was assessed by a self-reported questionnaire. Cross-sectional muscle area (CSMA) and bone parameters of radius (4% and 66% site) and tibia (66% site) were assessed using pQCT. Peak torque of biceps and quadriceps muscles was assessed by isokinetic dynamometry. Serum testosterone (T) and estradiol (E 2 ) levels were measured using immunoassays; free hormone fractions were calculated. Relations between indices of bone strength, CSMA, muscle strength, and sex steroids were studied using linear mixed-effects modeling. Physical activity, CSMA, and muscle strength were positively associated with indices of bone strength, except for volumetric BMD (vBMD). After controlling for age, weight, and height, free E 2 levels were positively associated with trabecular and cortical vBMD, negatively associated with endosteal circumference at the radius, and positively associated with cortical vBMD at the tibia. In addition, positive interactions between physical activity and serum E 2 concentrations were observed for bone size at the tibia. No associations between free T levels and pQCT bone parameters were found. In this population of healthy men at the age of PBM, parameters reflecting mechanical loading are confirmed as important determinants of bone size. E 2 , but not T, levels are positively associated with vBMD and modulate the impact of physical activity on bone size at the tibia.

Both sex steroid serum levels and body composition are under strong genetic control. Their interrelation is in part underlied by a genetic correlation, indicative of the action of shared genes.

Smoking is associated with lower areal bone mineral density (aBMD) and higher fracture risk, although most evidence has been derived from studies in elderly subjects. This study investigates smoking habits in relation to areal and volumetric bone parameters and fracture prevalence in young, healthy males at peak bone mass. Healthy male siblings (n ¼ 677) at the age of peak bone mass (25 to 45 years) were recruited in a cross-sectional population-based study. Trabecular and cortical bone parameters of the radius and cortical bone parameters of the tibia were assessed using peripheral quantitative computed tomography (pQCT). Areal bone mass was determined using dual energy X-ray absorptiometry (DXA). Sex steroids and bone markers were determined using immunoassays. Prevalent fractures and smoking habits were assessed using questionnaires. Self-reported fractures were more prevalent in the current and early smokers than in the never smokers ( p < .05), with a fracture prevalence odds ratio for early smokers of 1.96 (95% confidence interval 1.18-3.24) after adjustment for age, weight, educational level, and alcohol use and exclusion of childhood fractures. Current smoking was associated with a larger endosteal circumference (b ¼ 0.027 AE 0.009, p ¼ .016) and a decreased cortical thickness (b ¼ À0.034 AE 0.01, p ¼ .020) at the tibia. In particular, early smokers ( 16 years) had a high fracture risk and lower areal BMD, together with a lower cortical bone area at the tibia and lower trabecular and cortical bone density at the radius. An interaction between free estradiol and current smoking was observed in statistical models predicting cortical area and thickness (b ¼ 0.29 AE 0.11, p ¼ .01). In conclusion, smoking at a young age is associated with unfavorable bone geometry and density and is associated with increased fracture prevalence, providing arguments for a disturbed acquisition of peak bone mass during puberty by smoking, possibly owing to an interaction with sex steroid action. ß