Impaired bone microarchitecture and strength in patients with tumor-induced osteomalacia.

Some studies based on bone biopsy have demonstrated that in patients with tumor-induced osteomalacia (TIO) the mineralization process of the bone matrix is profoundly disturbed. However, the interrelationship between clinical and biochemical features and bone microarchitecture in this disease needs further analysis. With this purpose in mind, we set out three objectives: (i) to determine bone microarchitecture and estimated bone strength in a group of patients with tumor-induced osteomalacia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), (ii) to investigate correlations between duration of disease, biochemical features, bone density, HR-pQCT and FEA parameters, and (iii) to compare HR-pQCT and FEA parameters with a healthy control group. Ten patients with TIO were included. All patients had non-resolved disease. At the distal radius, all bone microarchitecture parameters were significantly affected in patients with TIO in comparison with healthy controls. At the distal tibia, all parameters were significantly impaired, except for trabecular thickness. All the parameters were more affected in the distal tibia than in the distal radius. Women with TIO (n = 7) had significantly lower bone strength parameters than healthy controls. In men (n = 3), bone strength parameters were significantly lower than in the control group at the distal tibia. Alkaline phosphatase levels exhibited a negative correlation with microarchitecture parameters, failure load, and stiffness. Higher levels of parathyroid hormone correlated with poorer microarchitecture parameters. We believe that in TIO, hormonal disturbances and the lack of mechanical stimulus specially converge to generate an extremely harmful combination for bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).

Burden of Disease in Patients With Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a chronic condition associated with muscle weakness and long-term disability. We conducted a cross-sectional study of patients diagnosed with TIO who had been referred to our institution between May 2018 and December 2019. Our aim was to assess health-related quality of life (HRQoL), fatigue, pain, and muscle mass and strength in these patients. Detailed information was obtained regarding general characteristics, initial symptoms and biochemical parameters measured at diagnosis and on the first visit to our institution. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, pain using the Brief Pain Inventory-Short Form (BPI-sf) scale and HRQoL by the 36-item Short Form survey (SF-36) questionnaire. Eight patients were included in the study: three without tumor localization, four with nonremission after surgery, and one with clinical recurrence 2 years after surgery. Fatigue experienced by patients with TIO was significantly higher compared to the general population (p ˂ .0001). The physical summary measure of the SF-36 showed significantly lower values than those of the Argentinean population with chronic conditions (mean 20.4 versus 45.9, p < .0001). According to the BPI-sf, patients with TIO have moderate average pain and the pain interferes severely with walking, general activities, work, and mood. Seven patients had a diagnosis of sarcopenia, four of which had severe sarcopenia. To our best knowledge, this is the first study aimed to quantify fatigue, pain, HRQoL, and muscle mass and strength in a group of patients with TIO. We hope our results contribute to a better understanding of the burden of disease and to establish a basis for future studies-with larger samples-which will make it possible to assess the efficacy of therapeutic interventions for these conditions. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Estudio retrospectivo observacional de los cambios del metabolismo mineral óseo post cirugía bariátrica / Observational retrospective study of changes in bone mineral metabolism after bariatric surgery

Introducción. Se ha descripto previamente que la cirugía bariátrica (CB) podría producir pérdida de la masa ósea dadas por alteraciones en el metabolismo mineral óseo. Se realizó este estudio con el objetivo de describir el impacto de la CB en el metabolismo óseo de pacientes en nuestro centro. Materiales y métodos. Estudio retrospectivo en el período 6/2007-3/2016. Se analizaron pacientes con datos de metabolismo óseo que requirieron CB. Se analizaron parámetros de laboratorio previos a la cirugía y a los 18 meses posteriores. Resultados. Se incluyeron 56 pacientes, con una mediana de edad de 47 años en un rango entre 26 y 70. Del total de los pacientes, 50 fueron intervenidos por gastrectomía vertical en manga y 6 por bypass gástrico. A pesar de no haber resultado estadísticamente significativos, se observó un incremento de los valores de vitamina D previos a la cirugía en comparación con este valor 18 meses posteriores (22 ng/ml vs 37 ng/ml respectivamente; p=0.194). Discusión. Se constató deficiencia de vitamina D prequirúrgica que revirtió en el pos operatorio, probablemente debido a la pérdida de peso, con la consiguiente liberación de la vitamina D secuestrada en el tejido adiposo, y a menor esteatosis y por consiguiente mayor metabolización hepática. Consideramos que es necesaria la realización de un estudio prospectivo con evaluación de la densidad mineral ósea en esta población de pacientes.(AU)

Association of nonalcoholic fatty liver disease with cardiovascular risk factors in obese adolescents: the role of interdisciplinary therapy.

BACKGROUND: Obesity is associated with several cardiovascular risk factors, including nonalcoholic fatty liver disease (NAFLD). These risk factors can induce changes in the arteries such as an increase in the carotid intima-media thickness (cIMT), which contributes to the early development of atherosclerosis. OBJECTIVE: To determine whether NAFLD is associated with an atherogenic lipid profile, inflammatory markers, or cIMT in obese adolescents and to compare the effects of therapeutic lifestyle changes in NAFLD and non-NAFLD groups. METHODS: A total of 79 obese adolescents were divided into two groups: 33 NAFLD and 46 non-NAFLD. They were submitted to an interdisciplinary therapy involving diet exercise and psychological support during the course of 1 year. The cIMT and estimates of fat mass (liver, intra-abdominal, and subcutaneous) were determined ultrasonographically. Body composition, glucose, lipid profile, and adipokines were analyzed before and after the therapy. RESULTS: At baseline, only in the NAFLD group was the homeostasis model assessment of insulin resistance positively correlated with cIMT and triglyceride/high-density lipoprotein cholesterol ratio. Therapy was associated with an increase in adiponectin concentrations and reduced visceral fat, cIMT, leptin, and plasminogen activator inhibitor-1 concentrations, as well as the ratios of total cholesterol/high-density lipoprotein cholesterol and triglycerides/high-density lipoprotein cholesterol in both groups. Only in the non-NAFLD group did therapy result in a reduction in the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and increased high-density lipoprotein cholesterol concentration. CONCLUSIONS: In obese adolescents, NAFLD is associated with cardiovascular risk factors and inflammatory markers of atherosclerosis that were positively correlated with cIMT only in the NAFLD group. Nevertheless, the strength of the present study is that the interdisciplinary therapy effectively improved cIMT and other proinflammatory adipokines in both groups.

Hyperleptinemia: implications on the inflammatory state and vascular protection in obese adolescents submitted to an interdisciplinary therapy.

The low-grade systemic inflammation seen in obesity may affect the actions of some adipose tissue-derived adipokines that are involved in the regulation of vascular function. We sought to verify whether hyperleptinemia may influence the inflammatory and atherogenic responses in obese adolescents undergoing interdisciplinary therapy. Thirty-four obese adolescents underwent interdisciplinary therapy for 1 year. Subjects were considered hyperleptinemic if they had baseline values of leptin above 20 ng/mL for boys and 24 ng/mL for girls. Both groups showed an improvement in body composition and a reduction in carotid intima-media thickness. However, only subjects in the non-hyperleptinemic group showed an increase in adiponectin concentration after therapy. Moreover, leptin concentration was positively correlated with adiponectin and inversely correlated with PAI-1 in this group. Hyperleptinemic state may impair the attenuation of inflammation in obese adolescents undergoing interdisciplinary therapy, particularly by impeding the increase in adiponectin concentration, which is directly involved in vascular protection.

Resistência insulínica pode prejudicar a redução da espessura mediointimal em adolescentes obesos / Insulin resistance can impair reduction on carotid intima-media thickness in obese adolescents

FUNDAMENTO: O processo aterosclerótico no nível endotelial começa em idade precoce e parece estar associado com a obesidade e suas comorbidades como a resistência insulínica. OBJETIVO: O objetivo deste estudo foi verificar a influência da resistência insulínica em marcadores inflamatórios e subclínicos de aterosclerose em adolescentes obesos. MÉTODOS: Sessenta e seis adolescentes obesos pós-púberes foram divididos em dois grupos de acordo com o índice de resistência insulínica estimado pelo Modelo de Avaliação da Homeostase (HOMA-RI): com resistência insulínica (RI) n = 39 e sem resistência insulínica (NRI) n = 27, e foram submetidos a uma intervenção interdisciplinar ao longo de um ano. A espessura mediointimal da artéria carótida comum (EMIC), e o tecido adiposo visceral e subcutâneo foram determinados por ultrassonografia. A composição corporal, pressão arterial, índice HOMA-RI, perfil lipídico e as concentrações de adipocinas [leptina, adiponectina, e inibidor do ativador do plasminogênio-1 (PAI-1)] foram analisados antes e após a terapia. RESULTADOS: Ambos os grupos apresentaram melhoras significativas na composição corporal, estado inflamatório (redução da concentração de leptina e PAI 1; aumento de adiponectina plasmática) e redução da EMIC. Apenas o grupo NRI mostrou correlação positiva entre as alterações na gordura visceral (∆Visceral) e mudanças na EMIC (∆ EMIC) (r = 0,42, p < 0,05). A análise por regressão linear simples revelou o ∆Visceral ser um preditor independente para a redução da EMIC nesse grupo (R2 ajustado = 0,14, p = 0,04). Os valores finais da EIMC permaneceram significativamente maiores no grupo RI, quando comparado com grupo NRI. CONCLUSÃO: A presença de resistência insulínica pode prejudicar mudanças na EMIC levando ao desenvolvimento precoce da aterosclerose em adolescentes obesos submetidos a uma intervenção interdisciplinar.

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Insulin resistance can impair reduction on carotid intima-media thickness in obese adolescents.

BACKGROUND: The atherosclerotic process at the endothelial level begins in early ages and seems to be associated with obesity and its comorbidities as insulin resistance. OBJECTIVE: The aim of this study was to verify the influence of insulin resistance on inflammatory and subclinical markers of atherosclerosis in obese adolescents. METHODS: Sixty-six post-pubescent obese adolescents were divided in two groups according to homeostasis model assessment of insulin resistance (HOMA-IR) measurement: with insulin resistance (IR) n=39 and without insulin resistance (NIR) n=27, and submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery intima-media thickness (cIMT), visceral and subcutaneous adipose tissue was determined by ultrasound. Body composition, blood pressure, HOMA-IR, lipid profile and adipokines concentrations [leptin, adiponectin, and plasminogen activator inhibitor type (PAI-1)] were analyzed before and after the therapy. RESULTS: Both groups presented significant improvements in body composition, inflammatory state (reduction of leptin and PAI-1 concentration; increasing of plasma adiponectin) and reduction of cIMT. Only NIR group showed positive correlation between changes in visceral fat (∆Visceral) and changes in cIMT (∆ cIMT) (r = 0.42; p < 0.05). Simple linear regression analyze revealed ∆Visceral to be an independent predictor to reduction of cIMT in this group (R2 adjusted = 0.14, p = 0.04). The final values of cIMT remained significantly higher in IR group when compared to NIR group. CONCLUSION: The presence of insulin resistance can impair changes in cIMT leading to early development of atherosclerosis in obese adolescents submitted to an interdisciplinary intervention..

[Ultraviolet radiation impact on seasonal variations of serum 25-hydroxy-vitamin D in healthy young adults in Buenos Aires]. / Variaciones estacionales de 25 (OH) vitamina D en jóvenes sanos y su asociación con la radiación ultravioleta en Buenos Aires.

Exposure to sunlight (ES) is the main source of vitamin D. There are few reports regarding the seasonal variations of serum 25(OH) vitamin D in young adults and its correlation with ultraviolet radiation dose (UVRd). Our aims were to determine 25OHD variations in young adults and assess the correlation between 25OHD levels, dietary calcium intake (DCI) and the UVRd. Eighty two healthy volunteers were prospectively studied: 42 women and 40 men. Serum 25OHD, calcium, phosphorus and magnesium were measured at the end of winter and at the end of summer. ES and UVRd were determined hourly in winter and summer. Seasonal variation in serum 25OHD levels was observed with significantly higher levels in summer in both gender. Serum 25OHD <20 ng/ml was more frequently found in winter (42.6% in women and 50% in men). The ES and UVRd were significantly lower in winter vs. summer. ES and UVRd positively correlated with 25OHD only in winter in both men and women. DCI was lower than recommended and did not correlate with 25OHD levels.

Variaciones estacionales de 25 (OH) vitamina D en jóvenes sanos y su asociación con la radiación ultravioleta en Buenos Aires / Ultraviolet radiation impact on seasonal variations of serum 25-hydroxyvitamin D in healthy young adults in Buenos Aires

El estatus de vitamina D depende principalmente de la exposición solar (ES). Son escasos los informes de las variaciones estacionales de 25(OH)vitamina D, 25OHD, en adultos jóvenes y su relación con la dosis de radiación solar ultravioleta (dRUV). El objetivo de este trabajo fue medir variaciones estacionales de 25OHD en adultos jóvenes estableciendo la correlación con la ingesta dietaria de calcio (IDCa) y la dRUV. Se realizó un estudio prospectivo en individuos sanos: 42 mujeres y 40 varones. Se dosaron a fin de invierno y fin de verano: 25OHD, calcio, fósforo y magnesio. Se evaluó ES y dRUV para cada hora del día en invierno y verano. Se observó una variación estacional de 25OHD con valores significativamente mayores en verano tanto en varones como en mujeres. El 42.6% de las mujeres y el 50.0% de los varones tenían 25OHD <20 ng/ml en invierno. La ES y la dRUV fueron significativamente inferiores en invierno que en verano. Sólo en invierno se halló una correlación positiva entre ES y dRUV con 25OHD en ambos sexos. La IDCa fue insuficiente y no correlacionó con 25OHD.

Exposure to sunlight (ES) is the main source of vitamin D. There are few reports regarding the seasonal variations of serum 25(OH) vitamin D in young adults and its correlation with ultraviolet radiation dose (UVRd). Our aims were to determine 25OHD variations in young adults and assess the correlation between 25OHD levels, dietary calcium intake (DCI) and the UVRd. Eighty two healthy volunteers were prospectively studied: 42 women and 40 men. Serum 25OHD, calcium, phosphorus and magnesium were measured at the end of winter and at the end of summer. ES and UVRd were determined hourly in winter and summer. Seasonal variation in serum 25OHD levels was observed with significantly higher levels in summer in both gender. Serum 25OHD <20 ng/ml was more frequently found in winter (42.6% in women and 50% in men). The ES and UVRd were significantly lower in winter vs. summer. ES and UVRd positively correlated with 25OHD only in winter in both men and women. DCI was lower than recommended and did not correlate with 25OHD levels.

Improvement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program.

The aim of this study was to verify whether a 1-year interdisciplinary weight-loss program improved common carotid artery intima-media thickness (IMT) and whether insulin resistance and/or inflammation (as measured by the markers plasminogen activator inhibitor type-1 and adiponectin) might underlie obesity in adolescents. A group of 29 post-pubescent obese adolescents were submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery IMT was determined ultrasonographically. Body composition, blood pressure (BP), glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile and adipokine concentrations were analyzed before and after the intervention. The interdisciplinary weight-loss program promoted a significant improvement in body composition, insulin concentration, HOMA-IR, lipid profile, BP and inflammatory state, in addition to significantly decreasing the common carotid artery IMT. Furthermore, this study demonstrated that the difference between baseline and final values of HOMA-IR (ΔHOMA-IR) was negatively correlated with concomitant changes in the adiponectin concentration (Δadiponectin; r=-0.42; P=0.02) and positively correlated with changes in common carotid artery IMT (Δcarotid IMT; r=0.41; P=0.03). Multiple regression analysis adjusted by age, cardiovascular risk factors and inflammatory markers showed that ΔHOMA-IR was an independent predictor of significant changes in common carotid artery IMT. This investigation demonstrated that an interdisciplinary weight-loss program promoted a reduction of the common carotid artery IMT in obese Brazilian adolescents, and the improvement of HOMA-IR was an independent predictor of carotid IMT changes in this population.