RESUMEN
BACKGROUND: Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS: In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS: A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION: This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.
Asunto(s)
Citrato de Calcio , Osteoporosis , Humanos , Femenino , Anciano , Masculino , Citrato de Calcio/efectos adversos , Calcio , Estudios Prospectivos , Osteoporosis/tratamiento farmacológico , Calcio de la Dieta , Suplementos Dietéticos/efectos adversosRESUMEN
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with progressive bone pain, muscle weakness, and fragility fractures. TIO is characterized by hypophosphatemia, excess renal phosphate excretion, and low/inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2 D) levels. Rarity and enigmatic clinical presentation of TIO contribute to limited awareness among the medical community. Accordingly, appropriate diagnostic tests may not be requested, leading to delayed diagnosis and poorer patient outcomes. We have developed a global guidance document to improve the knowledge of TIO in the medical community, enabling the recognition of patients with TIO and appropriate referral. We provide recommendations aiding diagnosis, referral, and treatment, helping promote a global standard of patient management. We reviewed the literature and conducted a three-round Delphi survey of TIO experts. Statements were drafted based on published evidence and expert opinions (≥70% consensus required for final recommendations). Serum phosphate should be measured in patients presenting with chronic muscle pain or weakness, fragility fractures, or bone pain. Physical examination should establish features of myopathy and identify masses that could be causative tumors. Priority laboratory evaluations should include urine/serum phosphate and creatinine to assess renal tubular reabsorption of phosphate and TmP/GFR, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25(OH)2 D, and FGF23. Patients with the clinical/biochemical suspicion of TIO should be referred to a specialist for diagnosis confirmation, and functional imaging should be used to localize causative tumor(s). Recommended treatment is tumor resection or, with unresectable/unidentifiable tumors, phosphate salts plus active vitamin D, or burosumab.
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Fracturas Óseas , Hipofosfatemia , Síndromes Paraneoplásicos , Humanos , Fosfatos/uso terapéutico , Hipofosfatemia/complicaciones , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Síndromes Paraneoplásicos/terapia , Dolor , Factores de Crecimiento de FibroblastosRESUMEN
This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.
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Fracturas Óseas , Deficiencia de Vitamina D , Humanos , Vitamina D/fisiología , Deficiencia de Vitamina D/epidemiología , Fracturas Óseas/tratamiento farmacológico , Huesos , Progresión de la EnfermedadRESUMEN
Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.
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Cirugía Bariátrica , Deficiencia de Vitamina D , Humanos , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/etiología , Suplementos Dietéticos , Vitaminas/uso terapéuticoRESUMEN
The therapeutic strategies for osteosarcoma involve both surgical approach and chemotherapy, but the identification of new therapeutic targets is particularly necessary in patients with local chemo-resistance, recurrence and lung metastases. The role of epigenetic regulation in osteosarcoma is largely unknown. Thus, in this study we disclosed the effects of histone deacetylase inhibitor drug PXD-101 on human osteosarcoma (OS) cell lines with different aggressiveness, including Saos-2, HOS and 143B cell lines. XTT assays revealed that treatment of Saos-2, HOS and 143B cells with PXD-101 decreased cell viability in a concentration-dependent manner. Fluorescence-activated cell sorting (FACS) analysis showed that PXD-101 inhibited proliferation and induced cell apoptosis. Wound healing assay indicated that PXD-101 inhibited migration of osteosarcoma cells. Real-Time RT-qPCR and protein analysis highlighted reduced expression of Runx2, Osterix and Mad2, probably due to Cyclin B1 inhibition by PXD-101 treatment. To our knowledge, this is the first study that characterized the anti-tumoral effect of PXD-101 in OS cells, suggesting a potential new therapeutic approach in osteosarcoma patients.
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Neoplasias Óseas , Osteosarcoma , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Epigénesis Genética , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Apoptosis , Neoplasias Óseas/genética , Movimiento CelularRESUMEN
This study reviews publications to describe the signs, symptoms and impact of tumour-induced osteomalacia (TIO) on patients' burden of disease. TIO is associated with a spectrum of signs and symptoms imposing a significant clinical burden, but the psychosocial impact of this rare disease has been poorly researched so far. INTRODUCTION: To describe the signs, symptoms and impacts of tumour-induced osteomalacia (TIO) and summarise the state of research on the burden of disease of this ultra-rare condition. METHODS: A targeted literature review was conducted in PubMed using pre-defined search terms. Relevant articles published between 1980 and 2021 were screened for inclusion. Seventy records were selected for analysis. Data were extracted and grouped into categories and sub-categories to identify recurrent signs, symptoms and impacts of TIO and describe the burden on patients. Chord diagrams were created to analyse the relationships between different TIO outcomes and characterise the presentation of TIO. RESULTS: Although the number of articles on TIO published have been increasing over the past 20 years, most studies were case reports and case series (n = 65/70) and only few were studies with higher quality of evidence (n = 5/70). Most articles were based on data reported by clinicians (n = 67/70). Patients with TIO experienced a combination of outcomes including chronic pain, weakness, skeletal-related manifestations and limitations in mobility. Only a few studies (n = 2/70) analysed the burden of TIO on the emotional wellbeing and on the work life of the patient. CONCLUSION: Patients with TIO present with a spectrum of signs and symptoms that impose a significant burden. The impact on the psychosocial wellbeing of patients should be further investigated, as this has been poorly researched so far. Studies with high quality of evidence should be designed to further the understanding of the burden of disease of TIO from the patient's perspective.
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Hipofosfatemia , Neoplasias de Tejido Conjuntivo , Osteomalacia , Costo de Enfermedad , Factores de Crecimiento de Fibroblastos , Humanos , Hipofosfatemia/etiología , Neoplasias de Tejido Conjuntivo/complicaciones , Osteomalacia/diagnóstico , Síndromes ParaneoplásicosRESUMEN
Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO. A search was conducted in Pubmed, Embase, Web of Science from inception until April 23rd, 2020. We selected case reports and case series of patients diagnosed with TIO, with information on tumor localization and serum phosphate concentration. Two reviewers independently extracted data on biochemical and clinical characteristics including bone involvement, tumor localization and treatment. 468 articles with 895 unique TIO cases were included. Median age was 46 years (range 9 months-90 years) and 58.3% were males. Hypophosphatemia and inappropriately low or normal 1,25-dihydroxyvitamin D levels, characteristic for TIO, were present in 98% of cases. Median tumor size was 2.7 cm (range 0.5 to 25.0 cm). Serum fibroblast growth factor 23 was related to tumor size (r = 0.344, P < 0.001). In 32% of the cases the tumor was detected by physical examination. Data on bone phenotype confirmed skeletal involvement: 62% of cases with BMD data had a T-score of the lumbar spine ≤ - 2.5 (n = 61/99) and a fracture was reported in at least 39% of all cases (n = 346/895). Diagnostic delay was longer than 2 years in more than 80% of cases. 10% were reported to be malignant at histology. In conclusion, TIO is a debilitating disease characterized by a long diagnostic delay leading to metabolic disturbances and skeletal impairment. Increasing awareness of TIO should decrease its diagnostic delay and the clinical consequences.
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Hipofosfatemia , Osteomalacia , Síndromes Paraneoplásicos , Diagnóstico Tardío/efectos adversos , Femenino , Factores de Crecimiento de Fibroblastos , Humanos , Masculino , Osteomalacia/diagnóstico , Osteomalacia/etiología , Osteomalacia/patología , Síndromes Paraneoplásicos/diagnósticoRESUMEN
Gorham-Stout disease (GSD) is a very rare disease characterized by increased bone erosion with angiomatous proliferation. The mechanisms underlying this disorder have not been deeply investigated. Due to its rarity, no guidelines are currently available for treatment and management of GSD. We recently evaluated the cellular alterations of the bone remodeling in patients showing that osteoclast precursors displayed increased ability to differentiate into osteoclasts and that affected osteoclasts resorb bone more actively than control cells. Moreover, osteoblasts isolated from a patient showed a defective ability to form mineralized nodules. In this paper, we investigated the molecular pathways involved in the cellular defects of GSD bone cells. For this study, we recruited nine patients and performed miRNome analysis of bone cells. Between the 178 miRNAs robustly expressed in GSD osteoclasts, significant modulation of three miRNAs (miR-1246, miR-1-3p, and miR-137-3p) involved in the regulation of osteoclast formation and activity or in the angiomatous proliferation was found in patients' cells. Interestingly, miR-1246 was also up-regulated in serum exosomes from patients. Analysis of miRNAs from patient osteoblasts suggested alteration of miR-204a-5p, miR-615-3p and miR-378a-3p regulating osteoblast function and differentiation. The resulting miRNA pattern may help to understand better the mechanisms involved in GSD and to identify new potential therapeutic targets for this rare disease.
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Huesos/citología , MicroARNs/genética , Osteoclastos/metabolismo , Osteocitos/metabolismo , Osteólisis Esencial/sangre , Adolescente , Huesos/metabolismo , Diferenciación Celular/genética , Niño , Exosomas/metabolismo , Femenino , Humanos , Masculino , MicroARNs/sangre , Osteólisis Esencial/fisiopatologíaRESUMEN
PURPOSE: The focus of SPINE20 is to develop evidence-based policy recommendations for the G20 countries to work with governments to reduce the burden of spine disease, and disability. METHODS: On September 17-18, 2021, SPINE20 held its annual meeting in Rome, Italy. Prior to the meeting, the SPINE20 created six proposed recommendations. These recommendations were uploaded to the SPINE20 website 10 days before the meeting and opened to the public for comments. The recommendations were discussed at the meeting allowing the participants to object and provide comments. RESULTS: In total, 27 societies endorsed the following recommendations. SPINE20 calls upon the G20 countries: (1) to expand telehealth for the access to spine care, especially in light of the current situation with COVID-19. (2) To adopt value-based interprofessional spine care as an approach to improve patient outcomes and reduce disability. (3) To facilitate access and invest in the development of a competent rehabilitation workforce to reduce the burden of disability related to spine disorders. (4) To adopt a strategy to promote daily physical activity and exercises among the elderly population to maintain an active and independent life with a healthy spine, particularly after COVID-19 pandemic. (5) To engage in capacity building with emerging countries and underserved communities for the benefit of spine patients. (6) To promote strategies to transfer evidence-based advances into patient benefit through effective implementation processes. CONCLUSIONS: SPINE20's initiatives will make governments and decision makers aware of efforts to reduce needless suffering from disabling spine pain through education that can be instituted across the globe.
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COVID-19 , Enfermedades de la Columna Vertebral , Anciano , Humanos , Italia , Pandemias/prevención & control , Enfermedades de la Columna Vertebral/terapiaRESUMEN
Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes.
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Fracturas Óseas , Osteoporosis , Humanos , Osteoporosis/tratamiento farmacológico , Difosfonatos/efectos adversos , Ácido Risedrónico/uso terapéutico , Alendronato/efectos adversosRESUMEN
Tumor-induced osteomalacia (TIO) is a rare, acquired condition of phosphate wasting due to phosphaturic mesenchymal tumors. Because the incidence and prevalence of TIO is unknown, we conducted an observational cohort study using national Danish health registers for the period 2008 to 2018 to obtain such information. The study also aimed to describe the demographics of the TIO population and the prognosis. The operational definition was based on hypophosphatemia or adult osteomalacia diagnoses, combined with prescriptions used in the initial management and procedures consistent with advanced imaging used for locating tumors. The incidence of TIO in Denmark was found to be below 0.13 per 100,000 person years for the total population of the country and 0.10 per 100,000 in adult-onset disease. The prevalence of TIO was estimated to be no more than 0.70 per 100,000 persons for the total population and 0.43 per 100,000 in adults. In 2018, there were a maximum of nine new cases of TIO in Danish adults. Mortality was low but few patients fulfilled the protocol cure criterion during the observation period. TIO has no ICD-10 code and limitations to the study include lack of information on serum biochemistry and on the use of phosphate supplements. Strengths include the use of long-term longitudinal, national hospital and prescription data from a country with universal healthcare. Given the very small patient population with TIO and the known delay to diagnosis and cure, management of patients with suspected TIO should be centralized.
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Hipofosfatemia , Neoplasias de Tejido Conjuntivo , Osteomalacia , Adulto , Estudios de Cohortes , Dinamarca/epidemiología , Factores de Crecimiento de Fibroblastos , Humanos , Osteomalacia/epidemiología , Síndromes ParaneoplásicosRESUMEN
OBJECTIVE: There are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls. METHODS: Seventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation. RESULTS: Patients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction). CONCLUSION: In a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.
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Hipercalcemia , Hiperparatiroidismo Primario , Calcio , Ecocardiografía , Femenino , Humanos , Hipercalcemia/epidemiología , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/diagnóstico por imagen , Hiperparatiroidismo Primario/epidemiología , Hormona ParatiroideaRESUMEN
Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.
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Proliferación Celular/efectos de los fármacos , Vesículas Extracelulares/genética , Osteosarcoma/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Antineoplásicos/efectos adversos , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Resistencia a Medicamentos/genética , Vesículas Extracelulares/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metástasis de la Neoplasia , Osteosarcoma/genéticaRESUMEN
BACKGROUND: The novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19. METHODS: This retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th. RESULTS: Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5-10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time. CONCLUSION: Xerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus.
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Infecciones por Coronavirus/epidemiología , Trastornos del Olfato/virología , Neumonía Viral/epidemiología , Trastornos del Gusto/virología , Xerostomía/virología , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , Estudios de Cohortes , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Trastornos del Olfato/epidemiología , Pandemias , Prevalencia , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Trastornos del Gusto/epidemiología , Xerostomía/epidemiologíaRESUMEN
Bone and muscle represent a single functional system and are tightly connected to each other. Indeed, diseases characterized by alterations of muscle physiology have effects on bone remodeling and structure and vice versa. Muscle influence on bone has been deeply studied, and recent studies identified irisin as new molecule involved in this crosstalk. Muscle regulation by bone needs to be extensively investigated since in the last few years osteocalcin was recognized as a key molecule in the bone-muscle interaction. Osteocalcin can exist in two forms with different degrees of carboxylation. The undercarboxylated form of osteocalcin is a hormone released by the bone matrix during the osteoclast bone resorption and can bind its G-protein coupled receptor GPRC6A expressed in the muscle, thus regulating its function. Recently, this hormone was described as an antiaging molecule for its ability to regulate bone, muscle and cognitive functions. Indeed, the features of this bone-related hormone were used to test a new therapeutic approach for sarcopenia, since injection of osteocalcin in older mice induces the acquirement of physical abilities of younger animals. Even if this approach should be tested in humans, osteocalcin represents the most surprising molecule in endocrine regulation by the skeleton.
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Huesos/fisiología , Ejercicio Físico , Músculo Esquelético/fisiología , Fenómenos Fisiológicos Musculoesqueléticos , Osteocalcina/metabolismo , Animales , Resorción Ósea/metabolismo , Humanos , Osteoclastos/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Osteoporosis (OP) is a multifactorial disorder in which environmental factors along with genetic variants and epigenetic mechanisms have been implicated. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of bone metabolism and OP aetiology. In this study, we analyzed the expression level and the genetic association of lncRNA GAS5 in OP patients compared to controls. Quantitative RT-PCR analysis of GAS5 was performed on the serum of 56 OP patients and 28 healthy individuals. OP subjects were divided into three groups of analysis: 29 with fragility fractures of lumbar spine (OP_VF), 14 with fragility fractures of femoral neck (OP_FF) and 13 without fractures (OP_WF). Genotyping of the rs145204276 insertion/deletion polymorphism has also been performed by Restriction fragment length polymorphism (RFLP) and direct sequencing analyses. Expression of circulating GAS5 is significantly increased in OP patients compared to controls (p < 0.01), with a statistically higher significance in fractured OP individuals vs. healthy subjects (p < 0.001). No statistically significant change was found in female OP patients; conversely, GAS5 is upregulated in the subgroup of fractured OP women sera (p < 0.01) and in all OP males (p < 0.05). Furthermore, a direct correlation between GAS5 expression level and parathyroid hormone (PTH) concentration was found in OP patients (r = 0.2930; p = 0.0389). Genetic analysis of rs145204276 revealed that the deletion allele was correlated with a higher expression of GAS5 in OP patients (0.22 ± 0.02 vs. 0.15 ± 0.01, ** p < 0.01). Our results suggest circulating GAS5 as a putative biomarker for the diagnosis and prognosis of OP and OP-related fractures.
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Ácidos Nucleicos Libres de Células/sangre , Regulación de la Expresión Génica , Osteoporosis/sangre , Fracturas Osteoporóticas/sangre , ARN Largo no Codificante/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 µg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS: We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Fracturas Osteoporóticas/prevención & control , Ácido Risedrónico/uso terapéutico , Teriparatido/uso terapéutico , Anciano , Anciano de 80 o más Años , Américas/epidemiología , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/efectos adversos , Método Doble Ciego , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/fisiopatología , Radiografía , Ácido Risedrónico/efectos adversos , Teriparatido/efectos adversosRESUMEN
OBJECTIVE: Kidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT. DESIGN: Cross-sectional study. PATIENTS: A total of 69 postmenopausal patients with PHPT and 41 healthy age- and sex-matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti-inflammatory drugs. MEASUREMENTS: We measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls. RESULTS: Mean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM-1/uCr was significantly higher in PHPT (1.4-6 ± 1.3-6 ) than controls (9.2-7 ± 7-7 ; P < .05); this was particularly evident in the CrCl 60-89 mL/min category (1.36 ± 97 vs 8.2-7 ± 3.6-7 ; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8-5 ± 1.4-5 and 1-5 ± 8-6 ; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01). CONCLUSIONS: We propose the utilization of these molecules, particularly urine KIM-1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease.