Sara Vandewalle

Bone size and bone strength are increased in obese male adolescents.

CONTEXT Controversy exists on the effect of obesity on bone development during puberty. OBJECTIVE Our objective was to determine differences in volumetric bone mineral density (vBMD) and bone geometry in male obese adolescents (ObAs) in overlap with changes in bone maturation, muscle mass and force development, and circulating sex steroids and IGF-I. We hypothesized that changes in bone parameters are more evident at the weight-bearing site and that changes in serum estradiol are most prominent. DESIGN, SETTING, AND PARTICIPANTS We recruited 51 male ObAs (10-19 years) at the entry of a residential weight-loss program and 51 healthy age-matched and 51 bone-age-matched controls. MAIN OUTCOME MEASURES vBMD and geometric bone parameters, as well as muscle and fat area were studied at the forearm and lower leg by peripheral quantitative computed tomography. Muscle force was studied by jumping mechanography. RESULTS In addition to an advanced bone maturation, differences in trabecular bone parameters (higher vBMD and larger trabecular area) and cortical bone geometry (larger cortical area and periosteal and endosteal circumference) were observed in ObAs both at the radius and tibia at different pubertal stages. After matching for bone age, all differences at the tibia, but only the difference in trabecular vBMD at the radius, remained significant. Larger muscle area and higher maximal force were found in ObAs compared with controls, as well as higher circulating free estrogen, but similar free testosterone and IGF-I levels. CONCLUSIONS ObAs have larger and stronger bones at both the forearm and lower leg. The observed differences in bone parameters can be explained by a combination of advanced bone maturation, higher estrogen exposure, and greater mechanical loading resulting from a higher muscle mass and strength.

Vitamin D binding protein, a new nutritional marker in cystic fibrosis patients.

Abstract Background: Vitamin D binding protein (DBP) is a multifunctional transport protein with a decreased serum concentration in cystic fibrosis (CF). The present study investigates the importance of DBP and its role as an alternative nutritional marker in CF. Methods: DBP phenotypes of 116 CF patients were determined electrophoretically. Serum DBP was measured by immunonephelometry. Parathormone was assessed by an immunoradiometric assay. Serum 25OH vitamin D3, 1,25(OH)2 vitamin D3 and leptin concentrations were determined by a radioimmunoassay. Serum α-tocopherol was measured by HPLC. Routine chemistry parameters were assessed using commercial methods. The Prognostic Inflammatory and Nutritional Index was calculated. Results: Decreased serum DBP concentrations were observed in the CF group. Total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride concentration, α-tocopherol and a low nutritional status correlated positively with DBP. Lipoprotein precipitation demonstrated a partial presence of DBP in very-low-density lipoprotein and LDL. Furthermore, DBP was positively correlated with serum leptin concentration. Conclusions: The present study demonstrates a positive correlation between DBP and serum lipids. Serum DBP concentration can be considered as a nutritional marker (especially for lipids). Clin Chem Lab Med 2008;46:365–70.

Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI).

PURPOSE To assess the evolution of body composition and bone metabolism in trans men during the first year of cross-sex hormonal therapy. METHODS In a prospective controlled study, we included 23 trans men (female-to-male trans persons) and 23 age-matched control women. In both groups, we examined grip strength (hand dynamometer), biochemical markers of bone turnover (C-terminal telopeptides of type 1 collagen (CTX) and procollagen 1 aminoterminal propeptide (P1NP)), total body fat and lean mass, and areal bone mineral density (aBMD) by dual-X-ray absorptiometry (DXA) and fat and muscle area at the forearm and calf, bone geometry, and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), before treatment and after 1 year of treatment with undecanoate (1000 mg i.m./12 weeks). RESULTS Before hormonal treatment, trans men had similar bone and body composition compared with control women. Testosterone treatment induced in trans men a gain in muscle mass (+10.4%) and strength and loss of fat mass (-9.7%) (all P<0.001) and increased the levels of P1NP and CTX (both P<0.01). Areal and volumetric bone parameters remained largely unchanged apart from a small increase in trabecular vBMD at the distal radius and in BMD at the total hip in trans men (P=0.036 and P=0.001 respectively). None of these changes were observed in the control group. CONCLUSIONS Short-term testosterone treatment in trans men increased muscle mass and bone turnover. The latter may rather reflect an anabolic effect of testosterone treatment rather than bone loss.

Estrogen-specific action on bone geometry and volumetric bone density: longitudinal observations in an adult with complete androgen insensitivity

INTRODUCTION Sex steroids have distinct effects on bone growth and maintenance in men and women, mediated through their respective steroid receptors. Though most evidence is derived from animal studies, several concepts have been confirmed in humans by detection of specific mutations. In this report we describe changes in bone size and volumetric bone density in a complete androgen insensitive subject (CAIS) due to a mutation in the androgen receptor during 5 years of estrogen treatment. MATERIALS AND METHODS We present a case report of a 31 year old XY female with CAIS with a longitudinal follow-up for 5 years of areal and volumetric bone parameters. Areal and volumetric bone parameters were determined using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Sex steroids, LH, FSH and IGF-I were determined by immunoassay. RESULTS Complete androgen insensitivity syndrome was genetically confirmed by detection of the mutation Asp767Tyr in the androgen receptor gene. Bone size at presentation was found to be intermediate between male and female reference values. Low areal and volumetric bone density (both trabecular and cortical) was observed at baseline and improved gradually with estrogen treatment (+2% to 6.5%). Upon estrogen treatment, endosteal contraction (-1%) was demonstrated, with increasing cortical thickness (+3%), cortical area (+5%) and unchanged periosteal circumference. CONCLUSIONS During adult life, estrogens mediate endosteal bone apposition and volumetric bone density, without marked influence on periosteal bone apposition. The finding of a bone size intermediate between male and female supports testosterone as an essential mediator for periosteal bone expansion, but not as the sole stimulus for bone expansion during growth.

Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy

OBJECTIVE Cross-sex hormonal therapy and sex reassignment surgery (including gonadectomy) in transsexual persons has an impact on body composition and bone mass and size. However, it is not clear whether baseline differences in bone and body composition between transsexual persons and controls before cross-sex hormonal therapy play a role. DESIGN A cross-sectional study with 25 male-to-female transsexual persons (transsexual women) before cross-gender sex steroid exposure (median age 30 years) in comparison with 25 age-matched control men and a male reference population of 941 men. MAIN OUTCOME MEASURES Areal and volumetric bone parameters using respectively dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), body composition (DXA), grip strength (hand dynamometer), Baecke physical activity questionnaire, serum testosterone and 25-OH vitamin D. RESULTS Transsexual women before cross-sex hormonal therapy presented with less muscle mass (p≤0.001) and strength (p≤0.05) and a higher prevalence of osteoporosis (16%) with a lower aBMD at the hip, femoral neck, total body (all p<0.001) and lumbar spine (p=0.064) compared with control men. A thinner radial cortex (p≤0.01) and lower cortical area at the radius and tibia (both p<0.05) was found in transsexual women vs. control men. Serum testosterone was comparable in all 3 groups, but 25-OH vitamin D was lower in transsexual women (p≤0.001). CONCLUSIONS Transsexual women before the start of hormonal therapy appear to have lower muscle mass and strength and lower bone mass compared with control men. These baseline differences in bone mass might be related to a less active lifestyle.

Sex Steroids in Relation to Sexual and Skeletal Maturation in Obese Male Adolescents

BACKGROUND Childhood obesity is associated with an accelerated skeletal maturation. However, data concerning pubertal development and sex steroid levels in obese adolescents are scarce and contrasting. OBJECTIVES To study sex steroids in relation to sexual and skeletal maturation and to serum prostate specific antigen (PSA), as a marker of androgen activity, in obese boys from early to late adolescence. METHODS Ninety obese boys (aged 10-19 y) at the start of a residential obesity treatment program and 90 age-matched controls were studied cross-sectionally. Pubertal status was assessed according to the Tanner method. Skeletal age was determined by an x-ray of the left hand. Morning concentrations of total testosterone (TT) and estradiol (E2) were measured by liquid chromatography-tandem mass spectrometry, free T (FT) was measured by equilibrium dialysis, and LH, FSH, SHBG, and PSA were measured by immunoassays. RESULTS Genital staging was comparable between the obese and nonobese groups, whereas skeletal bone advancement (mean, 1 y) was present in early and midadolescence in the obese males. Although both median SHBG and TT concentrations were significantly (P < .001) lower in obese subjects during mid and late puberty, median FT, LH, FSH, and PSA levels were comparable to those of controls. In contrast, serum E2 concentrations were significantly (P < .001) higher in the obese group at all pubertal stages. CONCLUSION Obese boys have lower circulating SHBG and TT, but similar FT concentrations during mid and late puberty in parallel with a normal pubertal progression and serum PSA levels. Our data indicate that in obese boys, serum FT concentration is a better marker of androgen activity than TT. On the other hand, skeletal maturation and E2 were increased from the beginning of puberty, suggesting a significant contribution of hyperestrogenemia in the advancement of skeletal maturation in obese boys.

Associations of Sex Steroids With Bone Maturation, Bone Mineral Density, Bone Geometry, and Body Composition: A Cross-Sectional Study in Healthy Male Adolescents

BACKGROUND Although both testosterone (T) and estradiol (E2) are considered essential in the regulation of the male skeleton, there are few data concerning the relative contribution of T and E2 on bone mineral density (BMD), bone geometry, and bone maturation in healthy boys. OBJECTIVE The objective of the study was to analyze the relationship between T and E2 and BMD, bone geometry, skeletal maturation, and body composition. METHODS This is a cross-sectional study in 199 healthy boys (aged 6-19 y). T and E2 were determined by liquid chromatography tandem mass spectrometry. Whole-body and lumbar areal bone mineral density (aBMD) and bone area, lean mass, and fat mass were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) volumetric BMD (vBMD) and bone geometry were assessed at the nondominant forearm and leg using peripheral quantitative computed tomography. Skeletal age was determined by an X-ray of the left hand. RESULTS T was positively associated with lean mass (P < .001), lumbar and whole-body bone area (P < .001), trabecular and cortical area (P < .01), and periosteal circumference (P < .01) at the radius. E2 was positively associated with lumbar and whole-body aBMD (P < .001), trabecular vBMD at the radius and tibia (P < .01), and cortical thickness at the radius (P < .05). E2 was an independent negative predictor of the endosteal circumference (P < .01). Moreover, E2 was positively associated with bone age advancement (P < .001). CONCLUSION Circulating E2 is positively associated with bone maturation and aBMD and vBMD and negatively with endosteal circumference in healthy boys, whereas T is a determinant of lean mass and bone size. These findings underscore the important role of E2 in skeletal development in boys.

Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis

Background/Objectives:The increase of bone disease in adult cystic fibrosis (CF) patients is partly attributed to inadequate serum concentrations of 25-OH cholecalciferol (25 (OH) D) blamed on fat malabsorption. Based on physiological, clinical and biochemical observations this pathogenesis is debatable. The objective was to ascertain the relative importance of different 25 (OH) D sources.Subjects/Methods:Over 4 consecutive years, 474 annual 25 (OH) D serum concentrations from 141 CF patients of all ages were compared with values of healthy peers and weighed against annual ultraviolet B (UVB) exposure.Results:Ranked per month, 25 (OH) D concentrations depicted a curve strikingly parallel to the amount of UVB exposure in the preceding months. A significant difference exists between 25 (OH) D concentrations in the ‘Months with high UVB exposure’ (May–October) and the ‘Months with low UVB exposure’ (November–April) but not with healthy controls in the same period.Conclusions:25 (OH) D concentrations clearly respond to the amount of sunshine in preceding months. They are not clearly influenced by daily oral supplements of 800 IU of cholecalciferol. Sun exposure should be encouraged, and the recommended dosage of oral supplements increased.

Genetic Variations in the Androgen Receptor Are Associated with Steroid Concentrations and Anthropometrics but Not with Muscle Mass in Healthy Young Men

Objective The relationship between serum testosterone (T) levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR) gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings. Design 677 men (25–45 years) were recruited in a cross-sectional, population-based sibling pair study. Methods Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs), sex steroid levels (by LC-MS/MS), body composition (by DXA), muscle cross-sectional area (CSA) (by pQCT), muscle force (isokinetic peak torque, grip strength) and anthropometrics were studied using linear mixed-effect modelling. Results Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT) and free T (FT) levels were positively related to muscle CSA, whereas estradiol (E2) and free E2 (FE2) concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats. Conclusions Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR gene also affect muscle mass or function.

Androgens and obesity in male adolescents

Purpose of reviewData on sex steroid levels and pubertal development in obese adolescent boys are scarce and contrasting. The present review summarizes the most recent results obtained with improved methodology to measure low sex steroid levels in children. Recent findingsObese pubertal boys have lower serum sex hormone–binding globulin and consequently lower total testosterone levels compared to normal-weight peers. However, during pubertal development, free testosterone levels in obese adolescents are not different from controls, indicating preserved androgen exposure as is additionally suggested by similar clinical genital staging (Tanner), serum gonadotropins levels, and serum prostate-specific antigen concentrations compared to nonobese adolescents. In pre and early puberty, total testosterone levels is not decreased, notwithstanding low sex hormone-binding globulin, and free testosterone is slightly increased in obese boys. This may result from increased adrenal activity as revealed by elevated serum androstenedione and dehydroepiandrosterone sulfate. In obese adolescent boys, increased aromatization of testosterone to estradiol tends to accelerate skeletal maturation. SummaryIn obese adolescent boys, free testosterone is a better index than total testosterone levels of androgen status, which is not different from nonobese controls. Increased aromatization of testosterone to estradiol underlies the dissociation between normal clinical sexual maturation and advanced skeletal maturation in the obese adolescent.