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SummaryIn this randomized double-blind placebo-controlled 24-week trial, cholecalciferol supplementation at 50,000 IU/week effectively improved bone microarchitecture parameters in juvenile-onset systemic lupus erythematosus (JoSLE) patients, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia site. An increase in the trabecular number and a decrease in the trabecular separation were observed, suggesting that vitamin D supplementation may be recommended for JoSLE patients with its deficiency.IntroductionVitamin D has an important effect on bone but there are no trials that directly address the boosting of serum levels of 25-hydroxyvitamin D (25OHD) in bone microarchitecture in JoSLE patients. The aim of this study was to evaluate the effect of vitamin D supplementation on bone microarchitecture parameters using HR-pQCT in JoSLE patients.MethodsThis study was a randomized double-blind placebo-controlled 24-week trial. Forty female JoSLE patients were randomized (1:1) to receive oral cholecalciferol at 50,000 IU/week (JoSLE-VitD) or placebo (JoSLE-PL). The medications remained stable throughout the study. Serum levels of 25OHD were measured using a radioimmunoassay. The bone microarchitecture and volumetric bone density were analyzed using HR-pQCT at tibia site.ResultsAt baseline, the groups were similar with respect to their age, body mass index, organ involvement, glucocorticoid dose, immunosuppressant use, serum 25OHD levels, and HR-pQCT parameters. After 24 weeks, higher 25OHD levels were observed in the JoSLE-VitD group compared to the JoSLE-PL group [31.3 (8.6) vs. 16.5 (5.8) ng/mL, p < 0.001]. An increase in the trabecular number [∆Tb.N 0.16 (0.24) vs. 0.03 (0.19) 1/mm, p = 0.024] and a decrease in the trabecular separation [∆ThSp −0.045 (0.067) vs. 0.001 (0.009) mm, p = 0.017] were found in the JoSLE-VitD group compared to the JoSLE-PL group at tibia site. No differences were observed in other structural parameters [trabecular (Tb.Th) or cortical thickness (Ct.Th)], volumetric bone mineral densities, cortical porosity, and biomechanical parameters (p > 0.05).ConclusionThis study suggests that cholecalciferol supplementation for 24 weeks effectively improved the bone microarchitecture parameters, mainly the trabecular number, in JoSLE patients.Trial RegistrationNCT01892748

Alcohol consumption is an issue of worldwide relevance and a problem of national scale in Mexico. The consumption pattern of large amounts of alcohol on the weekends is rapidly increasing in young adults between 18 and 29 years. Despite various studies that have focused on the noxious effect of alcohol in immunity, the changes in the immunoprofiles of peripheral blood cells have not been completely described. Natural killer cells (NKCs) are lymphoid-origin cells of the immune system that are responsible for defense against tumors, among other functions. In homeostatic conditions, they are found to be in a state of “dynamic balance” between activation and inhibition stimuli, which, if broken, may lead to immunosuppression or activation of cytotoxic mechanisms. In this study, we evaluated the immunoprofile of peripheral NKCs of 54 young adults, 29 of whom were binge drinkers and 25 of whom were low risk (LR), as classified by validated tools. Drinking habits were assessed. Blood samples were collected to perform hematic biometry and liver enzyme tests. Peripheral NKCs were identified by FACS, and stained for CCR2, CCR4, CCR5, CXCR4, CD69, CD127, CD137, TLR4, and Granzyme B. The data were analyzed using the t test and Mann–Whitney's U test for contrasts, and the effect size was obtained in order to evaluate the impact of each immunoprofile. The binge group showed increased expression of CCR5 and PD-1 in NKCs, respective to the LR group, and decreased expression of TLR4, along with fewer CCR4+ cells. Moreover, the increase found in CCR5 and PD-1 expression was correlated with the number of drinks in the last drinking session. Our findings show that young binge drinkers have different immunoprofiles that could suggest an early status of immunosuppression and trafficking of NKCs to the liver, which could be related to the onset of early liver damage, early in a subject's lifespan. •Binge drinking alters the immunoprofile of peripheral natural killer cells.•Young binge drinkers might have early liver damage undetected by commonly used blood tests.•Binge drinking could be related to an early stage of immunosuppression.•Activation and immunosuppression may occur simultaneously, due to the particular disarrangements in the immunoprofiles.

SummaryIn a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical).IntroductionThe aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS).MethodsHealthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500).ResultsAge-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson’s correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius.ConclusionThe current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.

SummaryIn a cross-sectional cohort of 450 healthy women aged 20 to 85 years, data on the density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) and were adjusted for age, weight, and height. Age-dependent patterns of change differed between the sites and between the trabecular and cortical compartments. In postmenopausal women, the trabecular bone remained relatively stable at the distal tibia, but the cortical compartment changed significantly. Cortical porosity exhibited a very weak correlation with stiffness.IntroductionThe aim of this study is to provide information on age-related, weight-related, and height-related changes in the volumetric bone mineral density (vBMD), structure, and biomechanical parameters of the cortical and trabecular compartments in a healthy female population using HR-pQCT.MethodsFor a cross-sectional Brazilian cohort of 450 women aged 20 to 85 years, age-related reference curves of the vBMD, structure, and biomechanical parameters of the distal radius (DR) and distal tibia (DT) were constructed and adjusted for weight and height, and comparisons between premenopausal and postmenopausal women were performed.ResultsReference curves were obtained for all parameters. At the DR, age-related changes varied from −8.68% (cortical thickness [Ct.Th]) to 26.7% (trabecular separation [Tb.Sp]). At the DT, the changes varied from −12.4% (Ct.Th) to 26.3% (Tb.Sp). Cortical porosity (Ct.Po) exhibited the largest percent changes: 342.2% at the DR and 381.5% at the DT. In premenopausal women, Ct.Th remained constant; in postmenopausal women, structural trabecular parameters (trabecular number (Tb.N), trabecular thickness (Tb.Th), Tb.Sp) did not change, whereas cortical parameters and stiffness were significantly altered. Cortical vBMD showed the greatest absolute decrease at both sites, and the slopes were highly negative after menopause. Pearson correlations between stiffness (S) and HR-pCT parameters revealed a significant correlation between the densities and structures of the trabecular and cortical compartments. A weak correlation was observed between S and Ct.Po (DR r = −0.162, DT r = −0.273; p < 0.05).ConclusionsThese data provide reference curves from healthy women and demonstrate that density and structural and biomechanical parameters differ between the radius and tibia and between the trabecular and cortical compartments. In postmenopausal women, the trabecular bone remained relatively stable at the tibia site, whereas the cortical compartment changed significantly.

SummaryIn X-linked hypophosphatemic (XLH) rickets, dual-energy X-ray absorptiometry (DXA) measurements must be analyzed with caution. High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex.IntroductionThe purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in 37 patients (13 children and 24 adults) with XLH confirmed by PHEX mutations from a tertiary center compared to healthy controls.MethodsAreal BMD (aBMD) was evaluated by DXA, whereas volumetric BMD (vBMD) and microarchitectural parameters were analyzed by HR-pQCT.ResultsAdult XLH patients had higher lumbar aBMD (p < 0.01) than the controls. At the radius, the vBMD was similar between XLH patients and controls. At the tibia, XLH patients had lower total vBMD (p = 0.04), likely resulting from decreased trabecular vBMD (p < 0.01), and this difference was observed in the children and adult groups. Analysis based on metabolic status showed that the adult XLH patients with non-compensated disease had lower cortical vBMD at the tibia than the compensated XLH patients (p = 0.03). The microarchitectural differences at the radius and tibia included lower trabecular number (p < 0.01), greater trabecular separation (p < 0.01), and higher trabecular network inhomogeneity (p < 0.01) in XLH patients compared to their controls. At the radius, adults exhibited greater trabecular deficits than were seen in children.ConclusionsIn XLH patients, DXA measurements must be analyzed with caution due to the interference of anatomic and anthropometric factors. HR-pQCT analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex.

SummaryRadius and tibia bone microarchitecture, analyzed through a high-resolution peripheral quantitative computed tomography, were significantly impaired in female patients with diffuse systemic sclerosis compared with healthy controls. Acroosteolysis, quality of life-grip strength, hand disability, and disease duration were significantly associated with this bone deterioration.IntroductionThe effect of diffuse systemic sclerosis (dSSc) on the bone is not completely understood. The objective of this study was to analyze the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical parameters at the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT) in female patients with dSSc and identify clinical and laboratory variables associated with these parameters.MethodsThirty-eight women with dSSc and 76 healthy controls were submitted to HR-pQCT at the distal radius and tibia. Clinical and laboratory findings, bone mineral density(BMD), nailfold capillaroscopy (NC), total passive range of motion(ROM), and quality of life (health assessment questionnaire—HAQ) were associated with HR-pQCT (Scanco Medical AG, Brüttisellen, Switzerland) parameters. Multiple linear regression models adjusted for clinical and laboratory variables, ROM and HAQ, were performed.ResultsDensity, microarchitecture, and biomechanical parameters at the distal radius and tibia were significantly impaired in dSSc patients compared with healthy controls (p < 0.001). Multiple linear regression models showed that lower trabecular density (Tb.vBMD) (radius R2 = 0.561, p = 0.002; and tibia R2 = 0.533, p = 0.005), and lower trabecular number (Tb.N) (tibia R2 = 0.533, p = 0.005) were significantly associated with acroosteolysis. Higher trabecular separation (Tb.Sp) was associated with disease duration and higher HAQ-grip strength (radius R2 = 0.489, p = 0.013), while cortical density (Ct.vBMD) was associated with ROM (radius R2 = 0.294, p = 0.002).ConclusionBone microarchitecture in patients with dSSc, analyzed through HR-pQCT, showed impairment of trabecular and cortical bone at distal radius and tibia. Variables associated with hand involvement (acroosteolysis, quality of life-grip strength, and ROM) and disease duration may be considered prognostic factors of this bone impairment.

Summary High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of female juvenile-onset systemic lupus erythematosus (JoSLE) patients revealed trabecular/cortical bone damage and reduced bone strength primarily at the distal radius compared to healthy controls. We demonstrated for the first time that JoSLE patients with vertebral fracture (VF) present trabecular impairment at the distal radius. Introduction This study investigated the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical features at the distal radius and tibia using HR-pQCT and laboratory bone markers in JoSLE patients compared to controls to determine whether this method discriminates JoSLE patients with or without VF. Methods We compared 56 female JoSLE patients to age- and Tanner-matched healthy controls. HR-pQCT was performed at the distal radius and tibia. Serum levels of the amino-terminal pro-peptide of type I collagen, the C-terminal telopeptide of type I collagen, intact parathormone, sclerostin, and 25-hydroxyvitamin D (25OHD) were evaluated. VFs were analyzed using VFA-dual-energy X-ray absorptiometry (DXA) (Genant’s method). Results Reduced density and strength parameters and microarchitecture alterations of cortical and trabecular bones were observed in JoSLE patients compared to controls, primarily at the distal radius ( p  < 0.05). Patients with VF exhibited a significant decrease in trabecular bone parameters solely at the distal radius (Total.BMD, p  = 0.034; Trabecular.BMD [Tb.BMD], p  = 0.034; bone volume (BV)/trabecular volume (TV), p  = 0.034; apparent modulus, p  = 0.039) and higher scores for disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), p  = 0.002). Bone metabolism markers were similar in all groups. Logistic regression analysis of parameters that were significant in univariate analysis revealed that Tb.BMD (OR 0.98, 95 % CI 0.95–0.99, p  = 0.039) and SLICC/ACR-DI (OR 7.37, 95 % CI 1.75–30.97, p  = 0.006) were independent risk factors for VF. Conclusion In conclusion, this study is the first demonstration of bone microstructure and strength deficits in JoSLE patients, particularly at the distal radius. Our results demonstrated that VF was associated with trabecular radius alteration and emphasized the potential detrimental effect of disease damage on this condition.

OBJECTIVE: The main objective of the study was to examine the effect of early life malnutrition on the relation between insulin sensitivity and abdominal adiposity in adulthood. It was hypothesised that participants with early life malnutrition would display a more pronounced deterioration of insulin sensitivity in association with a gain in abdominal fat. DESIGN: As a first attempt to investigate this issue, we studied the effect of body fat gains in a cross-sectional context. SUBJECTS: A total of 26 young adult men with evidence of malnutrition during the first year of life and 27 control subjects were recruited for this study. Malnutrition status was determined from medical files of paediatric hospitals in the Mexico City metropolitan area. MEASUREMENTS: Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp, and body composition was measured by anthropometrics, bioelectrical impedance and computed tomography. RESULTS: There was a negative correlation between total abdominal adipose tissue area and insulin sensitivity in the previously malnourished and control groups (r2=0.65 and 0.35, P<0.01, respectively). When matched for low amounts of abdominal fat (114 cm2), participants with and without early life malnutrition had similar insulin sensitivity (9.03 vs 8.88 mg kg-1 min-1). However, when matched for high amounts of abdominal fat (310 cm2) participants who were malnourished during the first year of life had lower insulin sensitivity (4.74 vs 6.85 mg kg-1 min-1, P<0.05). CONCLUSION: Higher levels of abdominal adipose tissue are more detrimental to insulin sensitivity in previously malnourished individuals.

Lack of agreement between the World Health Organization Category of impaired glucose tolerance and the American Diabetes Association category of impaired fasting glucose. F J Gómez-Pérez , C A Aguilar-Salinas , J C López-Alvarenga , J Perez-Jauregui , L E Guillen-Pineda and J A Rull Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico. Abstract OBJECTIVE: To study the concordance between the 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) category with the World Health Organization (WHO) impaired glucose tolerance (IGT) status in a population with a high prevalence of diabetes. RESEARCH DESIGN AND METHODS: We analyzed the oral glucose tolerance tests (OGTTs) carried out at the Instituto Nacional de la Nutrición Salvador Zubiran (INNSZ) central laboratory from June to December 1997. We included patients with fasting plasma glucose (FPG) between 60 and 160 mg/dl. The results from the glucose tolerance test were selected as the gold standard. RESULTS: Among the 1,802 glucose tolerance test results available for analysis, 1,706 fulfilled the requirements to be included. Diabetes and IGT were remarkably more frequently diagnosed when the WHO criteria were applied. The new ADA criteria failed to diagnose 69% of WHO diabetic patients and the vast majority of WHO glucose-intolerant subjects. Using the new criteria, 82% were considered normal. Of the IFG subjects, 39% were classified as diabetic and 23% were normal according to the 2-h postchallenge glucose values. Only 37% of the IFG patients were, in fact, glucose intolerant according to the WHO criteria. CONCLUSIONS: Our results clearly show that the 1997 ADA criteria are less sensitive for diagnosing diabetes than OGTT-based WHO criteria. Even more important, there is poor agreement between the WHO category of IGT and the ADA category of IFG.

The objective of this study was to measure the relation between menstrual cycle length disorders and degree of obesity. We enrolled 120 obese patients ages 18 to 40 y from an outpatient obesity clinic in a cross-sectional study. Patients with polycystic ovarian syndrome were excluded. Obesity was classified in five grades by relative weight. Waist-to-hip ratio was measured and comorbidities were assessed in each patient. Patients were asked to record menstrual cycle characteristics for 3 mo. Logistic regression analysis was performed, with age and type 2 diabetes as confounding variables. The patients’ mean age was 29.9 ± 6.4 y, the mean relative weight was 159.2 ± 26.6%, and the mean waist-to-hip ratio was 0.84 ± 0.1. Twenty-two (18.3%) patients had oligomenorrhea and 14 (11.7%) had amenorrhea. The risks for amenorrhea and oligomenorrhea were increased twofold by each unit increase of obesity grade. The odds ratio by waist-to-hip ratio tertile was not statistically significant. Type 2 diabetes and glucose intolerance were statistically significantly associated with amenorrhea and oligomenorrhea. Higher obesity grades were associated with higher probabilities of menstrual cycle disturbances such as amenorrhea and oligomenorrhea in this group of Mexican women.