Physiological declines in sex steroid exposure in relation to changes in body composition in healthy men-a prospective cohort study.

OBJECTIVE: Androgen levels decline from early adulthood and decreases are steeper in men with increasing body mass index. It is, however, unclear to what extent changes in other indices of body composition and metabolism associate with changes in sex steroid levels in healthy men. Therefore, this study investigated longitudinal changes in body composition and metabolic health in relation to sex steroid levels in healthy adult men. DESIGN: This is a longitudinal, population-based study. A total of 676 healthy men aged 24-46 years were measured at baseline and after ±12 years. METHODS: Serum sex hormone-binding globulin (SHBG) was measured by immunoassay, testosterone (T), estradiol (E2), and dihydrotestosterone byliquid chromatography with tandem mass spectrometry (LC-MS/MS), calculated free T and calculated free E2 (cFE2), and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. Grip strength was measured by hand-grip dynamometry. Body composition was determined using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. RESULTS: Mean fat mass (FM), lean mass (LM), and HOMA-IR increased (all P < .001). Decreasing androgen and SHBG levels was associated with increasing FM, whereas decreasing (cF)E2 levels were associated with decreasing FM (all P < .005). Decreasing (cF)E2 levels and increasing SHBG levels associated with decreasing LM (all P < .002). Changes in sex steroid levels and HOMA-IR or grip strength were not interrelated. CONCLUSION: Aging leads to increases in FM indices and insulin resistance, whereas changes in parameters of LM are less unequivocal. In healthy adult men, physiological changes in sex steroid exposure clearly correlate with changes in adiposity but not so with lean mass, insulin resistance, or grip strength. CLINICAL TRIAL: The SIBEX study was registered on ClinicalTrials.gov (#NVT02997033).

Bone parameters in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder: A comparative cross-sectional study.

OBJECTIVE: To compare bone parameters between individuals with hypermobile Ehlers-Danlos syndrome (hEDS) and generalized joint hypermobility spectrum disorder (G-HSD), both diagnosed according to the most recent diagnostic criteria, and with controls. METHODS: Twenty female adults with hEDS (mean age 43.8 years), 20 with G-HSD (mean age 41.8 years), and 37 healthy controls (mean age 40.8 years) participated. Body composition and bone parameters at whole body and lumbar spine were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography at the lower leg evaluated body composition (66 % site), and trabecular (4 % site) and cortical (66 % site) bone parameters at the tibia. RESULTS: No significantly different body composition and bone parameters were observed between hEDS and G-HSD. Compared to controls, individuals with hEDS and G-HSD had lower muscle mass (p = 0.004 and p < 0.001, respectively) and cross-sectional area (p = 0.025 and p < 0.001, respectively), cortical bone mineral content (BMC; p = 0.024 and p = 0.027, respectively) and area (p = 0.019 and p = 0.010, respectively). Additionally, individuals with hEDS had lower muscle density (p = 0.009), trabecular BMC (p = 0.027) and bone mineral density (p = 0.022), and individuals with G-HSD lower stress-strain index (p = 0.019), and periosteal and endosteal circumference (p = 0.002 and 0.025, respectively), compared to controls. CONCLUSION: Results indicated lower cortical bone mineral content and smaller cortices in hEDS and G-HSD compared to controls. Individuals with hEDS and G-HSD had no different bone parameters, suggesting that these impairments might not be reflected by the different diagnostic classification. Therefore, we recommend regular physical activity, and training to reduce the risk of falling in both hEDS or G-HSD.

Bone Mass, Density, Geometry, and Stress-Strain Index in Adults With Osteogenesis Imperfecta Type I and Their Associations With Physical Activity and Muscle Function Parameters.

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous heritable connective tissue disorder mainly characterized by bone fragility and increased fracture risk. This study investigated bone parameters in adults with OI type I and their relationship with physical activity and muscle function parameters in comparison with controls. A total of 27 (15 women, 12 men) adults with OI type I and 27 healthy age- and sex-matched controls, with mean age 45 years (range 18-72 years), were included. Peripheral quantitative computed tomography was performed at the lower leg and forearm to assess muscle density, muscle and fat cross-sectional area (CSA) (66% site), and trabecular (4% site) and cortical bone parameters (66% site) at radius and tibia. Physical activity (step count and moderate-to-vigorous physical activity [MVPA]) was assessed by accelerometry, muscle function parameters by Leonardo mechanography (single two-legged jump - peak power), and hand grip dynamometry (maximal hand grip strength). Overall, the OI type I group had significantly lower muscle CSA at the lower leg and forearm, lower trabecular and cortical bone mineral content, lower polar stress-strain index (SSIp), and smaller cortices but higher cortical bone mineral density and lower step count and MVPA in comparison with controls. Maximal hand grip strength was positively associated with SSIp at radius (p = 0.012) in the control group but not in the OI type I group (p = 0.338) (difference in associations: p = 0.012). No other significantly different associations between bone and muscle function parameters or physical activity (step count or MVPA) were found in the OI type I versus control group. We conclude that adults with OI type I have smaller bones, lower trabecular bone mass, lower estimates of bone strength, and higher cortical density in comparison with controls and that there are some indications of a disturbed biomechanical muscle-bone relationship in adults with OI type I. © 2022 American Society for Bone and Mineral Research (ASBMR).

Muscle Strength, Muscle Mass and Physical Impairment in Women with hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorder.

OBJECTIVES: To evaluate differences in physical impairment, muscle strength, muscle mass and muscle density between patients with hypermobile Ehlers Danlos Syndrome (hEDS), hypermobile spectrum disorder (HSD), and healthy controls. METHODS: Female adults with hEDS (n=20) and HSD (n=23), diagnosed to the most recent criteria, and age-matched healthy controls (n=28) completed the Arthritis Impact Measurement Scale (physical functioning) and performed maximal muscle strength and strength endurance tests of lower and upper limbs (hand grip, posture maintenance, 30 seconds chair rise and isokinetic tests). Muscle mass and density were evaluated by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. RESULTS: No differences in physical functioning and muscle strength were found between adults with hEDS and HSD. Furthermore, no differences in muscle mass and density were observed between the three groups. Nevertheless, when both patient groups were compared to controls, physical functioning, maximal muscle strength and muscle strength endurance were significantly lower (all p<0.001), except for the hand flexors. CONCLUSION: Physical functioning, muscle strength, density and mass did not significantly differ between individuals with hEDS and HSD. Compared to controls, physical functioning and muscle strength (maximal and endurance) were significantly lower. Consequently, (functional) strength training in individuals with hEDS and HSD is necessary.

Modest Changes in Sex Hormones During Early and Middle Adulthood Affect Bone Mass and Size in Healthy Men: A Prospective Cohort Study.

Bone metabolism in men is in part determined by sex steroid exposure. This is especially clear during puberty and senescence but it remains to be established whether declines in sex steroid levels during young and middle adulthood are associated with changes in bone mass and size. This study investigated changes in bone mineral content (BMC), areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone size in relation to sex steroid levels in 999 young adult men (age 24-46 years) of whom 676 were re-evaluated after a mean period of 12 years. Sex hormone-binding globulin (SHBG) levels were measured using immunoassay, testosterone (T) and estradiol (E2) using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and free fractions were calculated (cFT and cFE2, respectively). Areal bone parameters and BMC were measured at the hip and lumbar spine using dual-energy X-ray absorptiometry (DXA). Radial and tibial vBMD and bone size were determined using peripheral quantitative computed tomography (pQCT). Linear mixed models were used for statistical analyses. With aging, we observed decreases in almost all bone mass and density indices, whereas changes in bone geometry resulted in larger bones with thinner cortices. These changes in bone mass and size appeared related to sex steroid levels. Specifically, decreases in cFT (but not total T) levels were associated with larger decreases in lumbar spine BMC and especially with geometric changes in cortical bone at the tibia. Similarly, decreases in total E2 and cFE2 were associated with larger decreases in bone mass (all sites) and also with some geometric changes. Also increases in SHBG were independently associated with aging-related changes in bone mass and size in these men. In summary, even small changes in T, E2, and SHBG levels during young and middle adulthood in healthy men are associated with changes in bone mass and size. © 2022 American Society for Bone and Mineral Research (ASBMR).

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, 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.

Early Decline of Androgen Levels in Healthy Adult Men: An Effect of Aging Per Se? A Prospective Cohort Study.

CONTEXT: Androgen levels have been shown to decline in aging men. However, there is no consensus on the effect of aging, (changes in) body mass index (BMI), lifestyle factors, and intercurrent disease. OBJECTIVE: Investigating longitudinal changes in serum androgen levels in healthy men in relation to body composition, lifestyle factors, and intercurrent disease. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, population-based sibling pair study at a university research center. 999 healthy men aged 24 to 46 years of whom 691 were reevaluated after a mean period of 12 years. MAIN OUTCOME MEASURES: Serum SHBG, LH, and FSH levels measured using immuno-assays. Testosterone (T), estradiol (E2), dihydro-testosterone (DHT), and androstenedione (Adione) measured using liquid chromatography-tandem mass spectometry, free T calculated (cFT). RESULTS: Baseline age was 34 ±â€…6 years. Mean BMI increased by 1.19 kg/m2, T levels decreased by 14.2% (20.8 nmol/L vs. 17.8 nmol/L), cFT by 19.1% (392 pmol/L vs. 317 pmol/L), DHT by 15.6% (1.5 nmol/L vs.1.3 nmol/L), and Adione by 10.7% (3.7 nmol/L vs. 3.3 nmol/L; all P < 0.001). E2 did not change over time. SHBG increased by 3.0% (39.8 nmol/L vs. 41.0 nmol/L), LH by 5.8% (4.6 U/L vs. 4.9 U/L) and FSH by 14.7% (4.3 U/L vs. 5.1 U/L) (all P < 0.001). For T, cFT, DHT, Adione, and SHBG, these longitudinal changes persisted after adjustment for confounders (all P < 0.001). CONCLUSION: Serum androgen levels start declining early during adult life and independently from changes in BMI and other lifestyle factors, suggesting that aging per se leads to an altered sex steroid status. Given the concurrent rise in gonadotropin levels, the decline in androgen status most likely arises from primary decrease in testicular function.

Does Muscle Strength Change Over Time in Patients With Hypermobile Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorder? An Eight-Year Follow-Up Study.

OBJECTIVE: Reduced maximal muscle strength and strength endurance have been found in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder (hEDS/HSD) and are recognized as common associated features of the disorder. However, the extent to which these parameters change over time is currently not documented. Therefore, the purpose of this 8-year follow-up study was to investigate this evolution. METHODS: Thirty female patients (mean age 41 years) with hEDS/HSD and 17 controls participated at baseline and 8 years later. Maximal muscle strength and strength endurance tests of the knee flexors and extensors, and 2 lower-extremity posture maintenance tests were performed to evaluate static strength endurance. In addition, muscle mass and density were evaluated by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. RESULTS: Maximal muscle strength and strength endurance were significantly lower at both baseline and follow-up in the hEDS/HSD group compared to the control group (P ≤ 0.007). Maximal muscle strength of the knee flexors (decreased in the control group: pɳ2 = 0.139), strength endurance of the knee extensors (decreased in the hEDS/HSD group and increased in the control group: pɳ2 = 0.244), and muscle density (decreased in the hEDS/HSD group: pɳ2 = 0.263) showed a significantly different evolution over 8 years. No other significant differences in evolution were found. CONCLUSION: Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.