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.

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

UNLABELLED: Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. PURPOSE: The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. METHODS: In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-ß estradiol 100 µg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. RESULTS: Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). CONCLUSIONS: Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Relation of adrenal-derived steroids with bone maturation, mineral density and geometry in healthy prepubertal and early pubertal boys.

BACKGROUND: Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. OBJECTIVE: To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. METHODS: 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. RESULTS: Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). CONCLUSION: In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys.

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.

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.

Serum sclerostin levels in men with idiopathic osteoporosis.

OBJECTIVE: Sclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass, this might be reflected in higher serum sclerostin levels. METHODS: In 116 men with idiopathic osteoporosis (≤65 years old), 40 of their sons and healthy controls, areal bone parameters were measured using dual-energy X-ray absorptiometry, and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays and estradiol (E2) levels using liquid chromatography-tandem mass spectrometry. RESULTS: Men with idiopathic low bone mass had lower levels of sclerostin than the controls (0.54±0.17 vs 0.66±0.23 ng/ml; P<0.001). In both groups, sclerostin levels were strongly associated with age; when adjusting for age, no associations with anthropometrics were observed (P>0.14). In multivariate analyses, sclerostin levels displayed a positive association with whole-body bone mineral content (BMC) and areal BMD (aBMD), as well as with trabecular and cortical volumetric bone mineral density (vBMD) at the tibia in the probands. No clear associations were observed in the control group, neither were sclerostin levels associated with BMC at the radius or lumbar spine (all P>0.11). Testosterone, but not E2, was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons when compared with their controls. CONCLUSION: Lower rather than higher serum sclerostin levels in the probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects.

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.

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.

Microscale mechanisms of gas exchange in fruit tissue.

* Gas-filled intercellular spaces are considered the predominant pathways for gas transport through bulky plant organs such as fruit. Here, we introduce a methodology that combines a geometrical model of the tissue microstructure with mathematical equations to describe gas exchange mechanisms involved in fruit respiration. * Pear (Pyrus communis) was chosen as a model system. The two-dimensional microstructure of cortex tissue was modelled based on light microscopy images. The transport of O(2) and CO(2) in the intercellular space, cell wall network and cytoplasm was modelled using diffusion laws, irreversible thermodynamics and enzyme kinetics. * In silico analysis showed that O(2) transport mainly occurred through intercellular spaces and less through the intracellular liquid, while CO(2) was transported at equal rates in both phases. Simulations indicated that biological variation of the apparent diffusivity appears to be caused by the random distribution of cells and intercellular spaces in tissue. Temperature does not affect modelled gas exchange properties; it rather acts on the respiration metabolism. * This modelling approach provides, for the first time, detailed information about gas exchange mechanisms at the microscopic scale in bulky plant organs, such as fruit, and can be used to study conditions of anoxia.

[Dissociative phenomena: relationship to present and past stress]. / Dissociatieve verschijnselen: verband met stress uit heden én verleden.

BACKGROUND: Up till now research into dissociation has paid little attention to the relationship between current stress and family variables on the one hand and dissociative phenomena on the other hand. By contrast, however, many studies have investigated the link between traumatic experiences in the past and dissociative phenomena. AIM: To investigate, in a clinical population, whether dissociation is linked to current stress (within and outside the family) and to traumatic experiences in the past. METHOD: Dissociation was predicted on the basis of current stress (within and outside the family) and trauma by means of a multiple regression conducted on a population of patients with an eating disorder. RESULTS: Results indicated a clear link between current stress and dissociation. Patients with particularly high dissociation scores reported significantly more stress both on the measures of current stress and on the list of trauma. CONCLUSION: Dissociation is associated with stressful experiences, but not only with sexual trauma. Dissociation is also linked to stress experienced in current living conditions. Therefore the simple model that links dissociative experiences directly with trauma needs to be revised. This finding demonstrates that more attention should be given to stress factors in the treatment of dissociative phenomena.