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BACKGROUND: A substantial proportion of type 1 diabetes (T1D) patients free from known cardiovascular disease (CVD) show premature arterial stiffening, with age, blood pressure, and HbA1c-as gold standard of glycemic control-as main predictors. However, the relationship of arterial stiffness with other time-varying parameters of glycemic control and glycation has been far less explored. This study investigated the relationship of arterial stiffness with several short- and long-term parameters of glycemic control and glycation in patients with T1D, such as advanced glycation end-products (AGEs) and continuous glucose monitoring (CGM)-derived parameters. METHODS: Cross-sectional study at a tertiary care centre including 54 patients with T1D free from known CVD. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV). Current level and 10-year history of HbA1c were evaluated, and skin AGEs, urinary AGEs, and serum soluble AGE-receptor (sRAGE) concentrations. CGM for 7 days was used to determine time in range, time in hyper- and hypoglycemia, and glycemic variability. RESULTS: Cf-PWV was associated with current HbA1c (rs = + 0.28), mean 10-years HbA1c (rs = + 0.36), skin AGEs (rs = + 0.40) and the skin AGEs-to-sRAGE ratio (rs = + 0.40), but not with urinary AGE or serum sRAGE concentrations; and not with any of the CGM-parameters. Multiple linear regression for cf-PWV showed that the model with the best fit included age, T1D duration, 24-h mean arterial pressure and mean 10-years HbA1c (adjusted R2 = 0.645, p < 0.001). CONCLUSIONS: Longer-term glycemic exposure as reflected by current and mean 10-years HbA1c is a key predictor of arterial stiffness in patients with T1D, while no relationship was found with any of the short-term CGM parameters. Our findings stress the importance of early and sustained good glycemic control to prevent premature CVD in patients with T1D and suggest that HbA1c should continue to be used in the risk assessment for diabetic complications. The role of skin glycation, as a biomarker for vascular aging, in the risk assessment for CVD is an interesting avenue for further research.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Rigidez Vascular , Humanos , Lactente , Rigidez Vascular/fisiologia , Análise de Onda de Pulso , Automonitorização da Glicemia , Controle Glicêmico , Estudos Transversais , Glicemia , Receptor para Produtos Finais de Glicação Avançada , Produtos Finais de Glicação AvançadaRESUMO
This review discusses the changes in bone mass, structure, and metabolism that occur upon gender-affirming hormonal treatment (GAHT) in transgender adults and adolescents, as well as their clinical relevance. In general, available evidence shows that GAHT in transgender adults is not associated with major bone loss. In transgender adolescents, pubertal suppression with gonadotropin-releasing hormone agonist monotherapy impairs bone development, but at least partial recovery is observed after GAHT initiation. Nevertheless, a research gap remains concerning fracture risk and determinants of bone strength other than bone mineral density. Attention for bone health is warranted especially in adult as well as adolescent trans women, given the relatively high prevalence of low bone mass both before the start of treatment and after long-term GAHT in this population. Strategies to optimize bone health include monitoring of treatment compliance and ensuring adequate exposure to administered sex steroids, in addition to general bone health measures such as adequate physical activity, adequate vitamin D and calcium intake, and a healthy lifestyle. When risk factors for osteoporosis exist the threshold to perform DXA should be low, and treatment decisions should be based on the same guidelines as the general population.
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Osteoporose , Pessoas Transgênero , Adolescente , Adulto , Densidade Óssea , Desenvolvimento Ósseo , Feminino , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , TestosteronaRESUMO
OBJECTIVE: Acromegaly is accompanied by abnormalities in glucose and lipid metabolism which improve upon treatment. Few studies have investigated whether these improvements differ between treatment modalities. This study aimed to compare glucose homeostasis, lipid profiles and postprandial gut hormone response in patients with controlled acromegaly according to actual treatment. DESIGN: Cross-sectional study at a tertiary care centre. PATIENTS: Twenty-one patients with acromegaly under stable control (ie insulin growth factor 1 [IGF1] levels below sex- and age-specific thresholds and a random growth hormone level <1.0 µg/L) after surgery (n = 5), during treatment with long-acting somatostatin analogues (n = 10) or long-acting somatostatin analogues + pegvisomant (n = 6) were included. MEASUREMENTS: Glucose, insulin, total cholesterol and high-density lipoprotein-cholesterol were measured in fasting serum samples. Glucose, insulin, triglycerides, glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were measured during a mixed meal test. Insulin sensitivity was evaluated by a hyperinsulinaemic-euglycaemic clamp. RESULTS: There were no significant differences in glucose tolerance, insulin sensitivity or postprandial gut hormone responses between the three groups. Positive correlations between IGF1 levels and HbA1c, fasting glucose and insulin levels and postprandial area under the curve (AUC) of glucose and insulin and also an inverse association between IGF1 and glucose disposal rate were found in the whole cohort (all p < .05, lowest p = .001 for postprandial AUC glucose with rs = 0.660). CONCLUSION: In this cross-sectional study in patients with controlled acromegaly, there were no differences in glucose homeostasis or postprandial substrate metabolism according to treatment modality. However, a lower IGF1 level seems associated with a better metabolic profile.
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Acromegalia , Hormônio do Crescimento Humano , Acromegalia/tratamento farmacológico , Glicemia , Estudos Transversais , Glucose , Homeostase , Humanos , Insulina , Fator de Crescimento Insulin-Like IRESUMO
OBJECTIVE: Maternal age at childbirth is increasing worldwide, but studies investigating the consequences of this trend on offspring metabolic health are scarce. We investigated the associations of maternal age at childbirth with metabolic outcomes in adult male siblings. METHODS: We used data from 586 men aged 25-45 participating in a cross-sectional, population-based sibling-pair study, including maternal age at childbirth and offspring birthweight, adult weight, height, dual-energy X-ray absorptiometry (DXA)-derived body composition, blood pressure, and total cholesterol, glucose and insulin levels from fasting serum samples. Insulin sensitivity was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Maternal age at childbirth was 27·1 ± 4·7 years and was inversely associated with glucose levels (ß = -0·10, P = 0·022) and HOMA-IR (ß = -0·06, P = 0·065) in age- and body composition-adjusted analyses. Moreover, sons of younger (aged <25 and 25-29) and older (aged ≥35) mothers had higher HOMA-IR values than sons of mothers aged 30-34 (1·39, 1·35 and 1·42 vs 1·19, P = 0·028). Additional adjustment for birthweight did not substantially alter these results. Maternal age was inversely associated with cholesterol levels in unadjusted (ß = -0·09, P = 0·032), but not in age- and body composition-adjusted analyses. No associations of maternal age were observed with blood pressure, leptin, or adiponectin levels or with any of the body composition measurements. CONCLUSIONS: Increasing maternal age at childbirth is associated with lower fasting glucose levels and higher insulin sensitivity in adult male offspring. However, this association might not hold true in offspring of women aged ≥35 years at childbirth.
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Ordem de Nascimento , Resistência à Insulina , Idade Materna , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto JovemRESUMO
Jumping mechanography has been developed to estimate maximum voluntary muscle forces. This study assessed associations of jumping mechanography-derived force and power measurements with tibial cortical bone geometry, compared to other estimates of muscle mass, size, and function. Healthy men (n = 181; 25-45 years) were recruited in a cross-sectional, population-based sibling-pair study. Muscle parameters include isokinetic peak torque of the quadriceps, DXA-derived leg lean mass, mechanography-derived peak jump force and power, and pQCT-derived mid-tibial (66 %) muscle cross-sectional area (CSA). Mid-tibial cortical bone parameters were assessed by pQCT. In age, height, and weight-adjusted analyses, jump force and power correlated positively with cortical bone area, cortical thickness, and polar strength-strain index (SSIp) (ß = 0.23-0.34, p ≤ 0.001 for force; ß = 0.25-0.30, p ≤ 0.007 for power) and inversely with endosteal circumference adjusted for periosteal circumference (ECPC) (ß = -0.16, p < 0.001 for force; ß = -0.13, p = 0.007 for power). Force but not power correlated with cortical over total bone area ratio (ß = 0.25, p = 0.002). Whereas leg lean mass correlated with all cortical parameters except cortical over total bone area ratio (ß = 0.25-0.62, p ≤ 0.004), muscle CSA only correlated with cortical bone area, periosteal circumference, and SSIp (ß = 0.21-0.26, p ≤ 0.001), and quadriceps torque showed no significant correlations with the bone parameters. Multivariate models indicated that leg lean mass was independently associated with overall bone size and strength reflected by periosteal and endosteal circumference and SSIp (ß = 0.32-0.55, p ≤ 0.004), whereas jump force was independently associated with cortical bone size reflected by ECPC, cortical thickness, and cortical over total bone area ratio (ß = 0.13-0.28; p ≤ 0.002). These data indicate that jumping mechanography provides relevant information about the relationship of muscle with bone geometry.
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Fenômenos Biomecânicos/fisiologia , Músculo Quadríceps/fisiologia , Tíbia/anatomia & histologia , Tíbia/fisiologia , Adulto , Osso Cortical/anatomia & histologia , Osso Cortical/fisiologia , Estudos Transversais , Exercício Físico , Humanos , Masculino , Pessoa de Meia-Idade , IrmãosRESUMO
INTRODUCTION: At the start of gender reassignment therapy, persons with a gender identity disorder (GID) may deal with various forms of psychopathology. Until now, a limited number of publications focus on the effect of the different phases of treatment on this comorbidity and other psychosocial factors. AIMS: The aim of this study was to investigate how gender reassignment therapy affects psychopathology and other psychosocial factors. METHODS: This is a prospective study that assessed 57 individuals with GID by using the Symptom Checklist-90 (SCL-90) at three different points of time: at presentation, after the start of hormonal treatment, and after sex reassignment surgery (SRS). Questionnaires on psychosocial variables were used to evaluate the evolution between the presentation and the postoperative period. The data were statistically analyzed by using SPSS 19.0, with significance levels set at P < 0.05. MAIN OUTCOME MEASURES: The psychopathological parameters include overall psychoneurotic distress, anxiety, agoraphobia, depression, somatization, paranoid ideation/psychoticism, interpersonal sensitivity, hostility, and sleeping problems. The psychosocial parameters consist of relationship, living situation, employment, sexual contacts, social contacts, substance abuse, and suicide attempt. RESULTS: A difference in SCL-90 overall psychoneurotic distress was observed at the different points of assessments (P = 0.003), with the most prominent decrease occurring after the initiation of hormone therapy (P < 0.001). Significant decreases were found in the subscales such as anxiety, depression, interpersonal sensitivity, and hostility. Furthermore, the SCL-90 scores resembled those of a general population after hormone therapy was initiated. Analysis of the psychosocial variables showed no significant differences between pre- and postoperative assessments. CONCLUSIONS: A marked reduction in psychopathology occurs during the process of sex reassignment therapy, especially after the initiation of hormone therapy.
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Identidade de Gênero , Hormônios Esteroides Gonadais/uso terapêutico , Procedimentos de Readequação Sexual , Transexualidade/tratamento farmacológico , Transexualidade/psicologia , Ansiedade/psicologia , Depressão/cirurgia , Feminino , Humanos , Masculino , Estudos Prospectivos , Comportamento Sexual/psicologia , Inquéritos e QuestionáriosRESUMO
CONTEXT: treatment of primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism due to idiopathic hypercalciuria (SHPT-IH) is markedly different. Robust diagnostic tools to differentiate between both entities are however lacking. OBJECTIVE: evaluate the thiazide challenge test (TCT) in clinical practice, its aid in clinical decision making, evaluate the accuracy (sensitivity, specificity) and potentially useful parameters of the TCT. DESIGN: monocentric observational retrospective cohort study from January 2017 to November 2023. SETTING: outpatient, Ghent University Hospital (Belgium). PATIENTS: 25 adult patients with hypercalciuria, elevated parathyroid hormone (PTH), and high-normal or elevated serum calcium that underwent a TCT. INTERVENTION: TCT. OUTCOME MEASURES: serum, urinary biochemical parameters before and after testing, clinical and imaging outcomes, treatment, and follow-up. RESULTS: patients with a TCT-based working diagnosis of PHPT show greater increases in albumin-adjusted calcium and total serum calcium concentration than patients with SHPT-IH (+0,11 ± 0,10 vs. + 0,0071 ± 0,10mmol/l; p = 0,025 and +0,14 ± 0,12 vs. + 0,012 ± 0,15mmol/l; p = 0,024 respectively). The TCT-based working diagnosis of PHPT has a sensitivity of 81,8%, a specificity of 77,8% and a likelihood ratio of 3,68 of estimating a correct final diagnosis.Urinary calcium excretion, PTH, calcium-phosphorous ratio, PTH-inhibition rate, and parathyroid function index do not differ significantly in patients with PHPT compared to those with SHPT-IH. CONCLUSION: the TCT aids in discriminating patients with PHPT from those with SHPT-IH based on a rise in serum calcium. Other parameters are not different between both groups. Larger prospective trials are necessary to further define the diagnostic potential of the TCT, its most appropriate biochemical outcome variables, and decision cut-offs.
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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).
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Androgênios , Resistência à Insulina , Adulto , Masculino , Humanos , Estudos Prospectivos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Testosterona , Estradiol , Composição Corporal/fisiologia , Di-Hidrotestosterona , Globulina de Ligação a Hormônio Sexual/análiseRESUMO
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).
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Densidade Óssea , Osteogênese Imperfeita , Masculino , Humanos , Adulto , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Densidade Óssea/fisiologia , Força da Mão , Exercício Físico , MúsculosRESUMO
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).
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Densidade Óssea , Espectrometria de Massas em Tandem , Absorciometria de Fóton , Adulto , Cromatografia Líquida , Hormônios Esteroides Gonadais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testosterona , Adulto JovemRESUMO
Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.
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Fraturas Ósseas , Osteoporose , Bélgica/epidemiologia , Cálcio , Consenso , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Glucocorticoides/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológicoRESUMO
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 34â ±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 Pâ <â 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 Pâ <â 0.001). For T, cFT, DHT, Adione, and SHBG, these longitudinal changes persisted after adjustment for confounders (all Pâ <â 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.
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Envelhecimento/sangue , Androgênios/sangue , Adulto , Estudos de Coortes , Nível de Saúde , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testosterona/sangue , Adulto JovemRESUMO
[This corrects the article DOI: 10.3389/fendo.2021.641543.].
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X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.
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Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/terapia , Fator de Crescimento de Fibroblastos 23/metabolismo , Mutação , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Sociedades Médicas/organização & administração , Fosfatase Alcalina/metabolismo , Anticorpos Monoclonais Humanizados/administração & dosagem , Bélgica , Consenso , Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/genética , Humanos , Hipofosfatemia/complicações , Hipofosfatemia/genética , Comunicação Interdisciplinar , Osteomalacia/complicações , Osteomalacia/genética , Índice de Gravidade de Doença , Resultado do Tratamento , Vitamina DRESUMO
Biochemical markers of bone turnover are higher in young adult men than in middle-aged men or young adult women. Nonetheless, little is known about the determinants and clinical significance hereof. The present study examined determinants of serum bone turnover markers in men around peak bone mass age, and explored whether bone turnover at this age predicts subsequent changes in bone mass. We used cross-sectional and longitudinal data from 973 and 428 healthy men, respectively, aged 25 to 45 years at baseline, including baseline procollagen type I amino-terminal propeptide (P1NP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) from fasting serum samples, baseline questionnaire-assessed physical activity levels, and baseline and follow-up dual-energy X-ray absorptiometry-derived areal bone mineral density (aBMD) and body composition. Mean follow-up time was 12.4 ± 0.4 years. At baseline, all bone turnover markers were inversely associated with total body fat mass (ß ≤ -0.20, p < 0.001), and positively with physical activity during sports activities (ß ≥ 0.09, p ≤ 0.003), and, albeit not independently from fat mass, total body lean mass (ß ≥ 0.20, p ≤ 0.003). Mean annual aBMD changes in the longitudinal cohort were -0.19% ± 0.24% at the total body, -0.14% ± 0.42% at the spine, -0.49% ± 0.47% at the femoral neck, and -0.25% ± 0.37% at the total hip (all p < 0.001). Higher bone turnover markers at baseline were associated with larger decreases in aBMD at all measurement sites (ß ≤ -0.08, p ≤ 0.081 for P1NP; ß ≤ -0.16, p ≤ 0.002 for osteocalcin; and ß ≤ -0.21, p < 0.001 for CTX). In conclusion, our findings show that sports activities and body composition, primarily fat mass, are the main identified determinants of bone turnover in men around peak bone mass age. Further, bone turnover at this age is an important determinant of subsequent changes in bone mass, with higher levels of bone turnover markers being associated with greater decreases in aBMD. © 2017 American Society for Bone and Mineral Research.
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Remodelação Óssea/fisiologia , Reabsorção Óssea/fisiopatologia , Adulto , Biomarcadores/sangue , Composição Corporal , Densidade Óssea , Estudos Transversais , Exercício Físico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Context: In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry. Objective: We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass. Design, Setting, and Participants: Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center. Main Outcome Measures: Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts. Results: In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (ß ≤ -0.13, P < 0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels. Conclusion: In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry.
Assuntos
Osso Cortical/diagnóstico por imagem , Resistência à Insulina , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Absorciometria de Fóton , Adiponectina/metabolismo , Adulto , Glicemia/metabolismo , Composição Corporal , Densidade Óssea , Cromatografia Líquida , Colágeno Tipo I/metabolismo , Osso Cortical/patologia , Estradiol/metabolismo , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Força Muscular , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Tamanho do Órgão , Osteocalcina/metabolismo , Hormônio Paratireóideo/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Rádio (Anatomia)/patologia , Albumina Sérica/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , Espectrometria de Massas em Tandem , Testosterona/metabolismo , Tíbia/patologia , Tomografia Computadorizada por Raios X , Vitamina D/análogos & derivados , Vitamina D/metabolismoRESUMO
Context: The increased fracture risk associated with type 1 diabetes mellitus (T1DM) remains unexplained by traditional risk factors such as low areal bone mineral density (aBMD). Nonetheless, few data exist on other determinants of bone strength in T1DM, including volumetric bone mineral density (vBMD) and bone geometry. Objective: We compared areal and volumetric bone parameters and cortical bone geometry in adult T1DM patients and sex- and age-matched controls. Design: Cross-sectional study including 64 adult T1DM patients (38 men; mean age, 41.1 ± 8.1 years) and 63 sex- and age-matched controls. Main Outcome Measures: Areal bone parameters using dual-energy X-ray absorptiometry; volumetric bone parameters and cortical bone geometry using peripheral quantitative computed tomography. Results: T1DM was associated with lower aBMD at the total body, femoral neck, and total hip; lower trabecular vBMD at the distal radius; and higher cortical but lower total vBMD at the radial shaft. In addition, subjects with T1DM had a similar periosteal but larger endosteal circumference, smaller cortical thickness, and lower cortical over total bone area ratio. Differences in bone parameters could not be explained by differences in bone turnover markers or body composition, but cortical area was inversely associated with glycemic variability and long-term glycemic control. Conclusions: Besides decreased aBMD and trabecular vBMD, adult T1DM patients present with a cortical bone size deficit, which may contribute to their increased fracture risk. This deficit is mainly situated at the endosteal envelope, suggesting imbalanced remodeling rather than compromised modeling processes as the underlying mechanism.