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.

Clinical MEN-1 Among a Large Cohort of Patients With Acromegaly.

CONTEXT: Clinical multiple endocrine neoplasia type 1 (MEN-1) is diagnosed by the presence of at least 2 MEN-1-associated tumors. Many patients with acromegaly and clinical MEN-1 yield negative testing for MEN1 mutations. While cases of acromegaly and primary hyperparathyroidism (PHP) with negative genetic testing have been reported, its prevalence among patients with acromegaly is undetermined, and the clinical presentation has not been well characterized. OBJECTIVES: The main goals of this study are: (1) To determine the prevalence of clinical MEN-1 with PHP in patients with acromegaly and characterize their clinical features; and (2) to evaluate the genetic basis for the coexistence of acromegaly and PHP. DESIGN: Retrospective record review and genetic analysis. SETTING: Clinical Research Centers. PARTICIPANTS: 414 patients with acromegaly. INTERVENTIONS: Clinical evaluation and DNA sequencing for MEN1, CDKN1A, CDKN1B, CDKN2B, CDKN2C, and AIP genes. MAIN OUTCOME MEASUREMENTS: Clinical and genetic analysis. RESULTS: Among patients with acromegaly, clinical MEN-1, as defined by the presence of at least one other MEN-1-associated tumor, was present in 6.6%. PHP occurred in 6.1%; more than half had parathyroid hyperplasia. DNA sequencing was unrevealing for genetic mutations, except for 1 case of a CDC73 mutation. Acromegaly was diagnosed at an older age with a higher prevalence of malignancies (specifically breast and thyroid) in patients with coexisting PHP than those with isolated acromegaly. CONCLUSIONS: A distinct phenotype is described in patients with clinical MEN-1 and negative genetic testing for mutations previously associated with this syndrome. Further studies are needed to identify other genes that may explain the association between PHP and acromegaly.

Mesa 3: Diabetes Mellitus Tipo 2 y actividad física / Table 3: Type 2 diabetes and physical activity

La prevalencia de diabetes mellitus (DM) actividad física es cada vez mayor asociada a bajos niveles de actividad física (AF) y aumento de sobrepeso-obesidad. Los beneficios de la AF incluyen la prevención de la DM, reducción de hemoglobina glicosilada y glucemia postprandial, mejoría del perfil cardiovascular (descenso Presión arterial y triglicéridos, aumento de colesterol HDL), descenso significativo de biomarcadores proinflamatorios. Además, la AF mejora la disfunción sexual, la función endotelial, el óxido nítrico biodisponible y la insulinosensibilad, incrementa la testosterona, mejora el humor y la autoestima, la ansiedad y la depresión. El ejercicio incrementa la producción de glucosa, la secreción de insulina compensatoria está alterada y se exacerba por una mayor secreción de catecolaminas. Las personas con insulinopenia marcada tienen riesgo de cetosis. El aumento de hipoglucemias está dado por una mayor captación de glucosa. La AF mejora la polineuropatía y la neuropatía autonómica cardíaca, previene la enfermad renal crónica y se asocia a menores niveles de retinopatía diabética. En pacientes con retinopatía preproliferativa y proliferativa o degradación macular, se desaconsejan las actividades que aumentan considerablemente la presión intraocular. Está contraindicado el ejercicio en caso de hemorragia vítrea. El requerimiento energético depende del tipo, intensidad y duración del ejercicio. Se debe considerar el cuidado del pie. Las recomendaciones son disminuir el tiempo sedentario, ejercicio aeróbico al menos 150 min/semana y ejercicio de resistencia. Al aumentar la intensidad o ante riesgo elevado se debe realizar chequeo que incluya electrocardiograma y test de esfuerzo. Considerar ecocardiograma bidimensional y doppler