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Vertebral fractures (VFs) are the most common osteoporotic fractures in the general population, and they have been associated with high mortality, decreased quality of life, and high risk of subsequent fractures, especially when recent, multiple, or severe. Currently, VF diagnosis and classification determine fracture risk and the most appropriate anti-osteoporotic treatment. However, VFs are clearly underdiagnosed, especially in patients with chronic kidney disease (CKD), and CKD-associated osteoporosis has been disregarded until recently. VFs are associated with higher morbidity and mortality, and their prevalence and incidence differ depending on the grade of renal dysfunction (CKD G1-G5) and/or the type of renal replacement therapy (dialysis or transplantation). In addition to classical risk factors [such as higher age, female sex, reduced bone mineral density, diabetes and steroid use], various other factors have been associated with an increased risk of VFs in CKD, including CKD grade, haemodialysis vintage, time since renal transplantation, low or high intact parathyroid hormone and phosphate levels, and/or vitamin D and K1 deficiencies. Importantly, several clinical societies have recently modified their algorithms according to the fracture risk classification (including the presence of VFs) and determined the most appropriate anti-osteoporotic treatment for the general population. However, there are no specific guidelines addressing this topic in patients with CKD despite an important paradigm shift regarding the prognostic value of bone mineral density in 2017 after the publication of the CKD-Mineral and Bone Disorder Kidney Disease: Improving Global Outcomes guidelines. A proactive attitude towards diagnosis, treatment, and research is proposed to avoid therapeutic nihilism.
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The evolution of pain and quality of life after a symptomatic vertebral fracture differs according to patient gender, with a worse evolution in women independently of the treatment received. PURPOSE: In a previous randomized clinical study comparing the effect of vertebroplasty (VP) vs. conservative therapy (CT) on pain evolution and quality of life (QoL) of patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain in 23% of subjects, independently of the therapy received. This study analyses the effect of gender on the evolution of pain and QoL in these subjects. METHODS: 118/125 randomized patients (27 males/91 females) with recent symptomatic VFs were evaluated. All received a standardized analgesic and antiosteoporotic format of treatment. Pain and QoL were evaluated by VAS and Qualeffo-41, respectively, at baseline, at 2 weeks and 2 and 6 months. We compared pain evolution and QoL after treatment (CT vs. VP) according to gender, and analysed factors including age, time of evolution, treatment received, baseline VAS, previous VFs (total and recent), incidental VFs, lumbar and femoral T-scores, and analgesic and antiosteoporotic treatment. RESULTS: At baseline, there were no differences in age (males 74.8 ± 11.2 vs. females:73.2 ± 8.7 years), time of evolution, number of VFs (males:3.8 ± 2.4 vs. females: 3.1 ± 2.4), treatment received (VP, males:59%, females:45%), lumbar or femoral T-score, baseline VAS (males:6.8 ± 2.1 vs. females:6.8 ± 2.2) or Qualeffo score (males:52.2 ± 24.4 vs. females:59.7 ± 20.6). Pain and QoL evolution differed according to gender, being better in males. These differences were significant after two months independently of the treatment and the development of incidental VF during follow-up. CONCLUSIONS: Pain and QoL evolution after a symptomatic VF differs according to gender, with a worse evolution in women independently of the treatment received.
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Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Masculino , Humanos , Femenino , Calidad de Vida , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Dolor de Espalda , Analgésicos/uso terapéutico , Fracturas Osteoporóticas/cirugíaRESUMEN
Nearly 10% of subjects with severe idiopathic osteoporosis present pathogenic WNT1 mutations. Clinical characteristics include a family history of osteoporosis, early adulthood onset, and fragility fractures which may evolve to pseudoarthrosis. WNT1 should be genetically screened in these patients as the phenotype is often variable and therapeutic approaches may differ. INTRODUCTION: Recent studies have shown that homozygous WNT1 gene mutations may be related to severe osteoporosis resembling osteogenesis imperfecta (OI). Conversely, heterozygous WNT1 mutations are linked to a milder phenotype of early-onset osteoporosis. Treatment with bisphosphonates is reported to be unsatisfactory. Our aim was to analyze the presence and prevalence of WNT1 mutations and the main associated clinical characteristics in subjects with primary early-onset osteoporosis. METHODS: A cohort comprising 56 subjects (aged 19-60 years) with severe, early-onset osteoporosis was screened by massive parallel sequencing with a 23-gene panel. The gene panel included 19 genes known to cause OI (including the WNT1 gene), three genes related to osteoporosis, and the gene related to hypophosphatasia (ALPL). RESULTS: We identified five patients (3 men) with heterozygous WNT1 variants. All presented severe osteoporosis with early fracture onset and a family history of fragility fractures. None presented a characteristic phenotype of OI or skeletal deformities. One patient was previously treated with bisphosphonates, presenting inadequate response to treatment and two developed pseudoarthrosis after upper arm fractures. All subjects were diagnosed in adulthood. CONCLUSIONS: Nearly 1/10 adult subjects with severe idiopathic osteoporosis may present pathogenic WNT1 mutations. Clinical characteristics commonly include a family history of osteoporosis, onset in early adulthood, marked decrease in bone mass, and prevalent fractures, particularly vertebral. WNT1 should be genetically screened in these subjects as the phenotype is often variable and the therapeutic approach may differ. The role of WNT1 mutations in the development of pseudoarthrosis should also be elucidated.
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Osteoporosis , Proteína Wnt1 , Humanos , Difosfonatos/uso terapéutico , Fracturas del Húmero , Mutación , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/diagnóstico , Osteoporosis/genética , Osteoporosis/tratamiento farmacológico , Seudoartrosis/tratamiento farmacológico , Proteína Wnt1/genéticaRESUMEN
BACKGROUND: X-linked hypophosphatemic osteomalacia (XLH) is an inherited disorder that can cause highly disabling musculoskeletal comorbidities in adulthood. OBJECTIVE: To analyze the clinical-radiological characteristics, comorbidities and complications associated with the disease and treatment in an adult population with XLH. METHOD: Retrospective study of patients treated for XLH in a rheumatology department in the last 10 years, evaluating the clinical-radiological findings, comorbidities and associated complications. RESULTS: Five patients between 39 and 75 years of age were included. All had short stature, osteoarticular symptoms and radiological enthesopathy. Four patients had early degenerative arthropathy of the knees and hips, and dental alterations associated with their disease. All patients older than 50 years required some type of prosthetic replacement. Two patients had femoral stress fractures, one had renal lithiasis and another developed tertiary hyperparathyroidism. CONCLUSIONS: Musculoskeletal manifestations are frequent and disabling in the adult population with XLH, so proper diagnosis and management from childhood are essential to prevent the development of complications in adulthood associated with this disease.
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Raquitismo Hipofosfatémico Familiar , Enfermedades Genéticas Ligadas al Cromosoma X , Osteomalacia , Humanos , Adulto , Niño , Osteomalacia/etiología , Estudios Retrospectivos , Raquitismo Hipofosfatémico Familiar/complicaciones , Raquitismo Hipofosfatémico Familiar/diagnóstico , Raquitismo Hipofosfatémico Familiar/terapia , Radiografía , Factores de Crecimiento de FibroblastosRESUMEN
Introduction: Osteoporosis is a chronic progressive bone disease characterized by low bone mineral density (BMD) and micro-architectural deterioration of bone tissue, leading to an increase in bone fragility and the risk of fractures. A well-known risk factor for bone loss is postmenopausal status. Beer may have a protective effect against osteoporosis associated with its content of silicon, polyphenols, iso-α-acids and ethanol, and its moderate consumption may therefore help to reduce bone loss in postmenopausal women. Methods: Accordingly, a 2-year controlled clinical intervention study was conducted to evaluate if a moderate daily intake of beer with (AB) or without alcohol (NAB) could have beneficial effects on bone tissue. A total of 31 postmenopausal women were assigned to three study groups: 15 were administered AB (330 mL/day) and six, NAB (660 mL/day), whereas, the 10 in the control group refrained from consuming alcohol, NAB, and hop-related products. At baseline and subsequent assessment visits, samples of plasma and urine were taken to analyze biochemical parameters, and data on medical history, diet, and exercise were collected. BMD and the trabecular bone score (TBS) were determined by dual-energy X-ray absorptiometry. Markers of bone formation (bone alkaline phosphatase [BAP] and N-propeptide of type I collagen [PINP]) and bone resorption (N-telopeptide of type I collagen [NTX] and C-telopeptide of type I collagen [CTX]) were determined annually. Results: Bone formation markers had increased in the AB and NAB groups compared to the control after the 2-year intervention. However, the evolution of BMD and TBS did not differ among the three groups throughout the study period. Discussion: Therefore, according to the findings of this pilot study, moderate beer intake does not seem to have a protective effect against bone loss in early post-menopausal women.
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Bilirubin and bile acids have deleterious effects on osteoblasts, which may explain the low bone formation of liver diseases with cholestasis. Although there is some clinical evidence of increased bone resorption in this condition, the effects of these substances on osteoclasts are unknown. The objective was to analyze the effects of bilirubin and bile acids -lithocholic acid (LCA) and ursodeoxycholic acid (UDCA)- on osteoclast viability and apoptosis, and on the expression of osteoclast-related microRNAs (miRNAs). RAW 264.7 cells and human PBMCs were differentiated into osteoclasts. Success in differentiation was assessed by TRAP stain and osteoclast-specific gene expression; osteoclast activity was detected by the resorption pits in Corning® Osteo Assay Surface Plates. Cells were treated with camptothecin (CAM) or with bilirubin, LCA or UDCA, at several concentrations and combinations, including non-treated cells as control. Cell viability was measured using WST-1 assay and apoptosis assessing Caspase-3 by Western blot. Expression of miR-21a, miR-29b, miR-31, miR-148a, miR-155 and miR-223 were analyzed by Real Time. Viability increased gradually in osteoclasts differentiated from RAW 264.7 cells, as the concentration of bilirubin increased, being particularly high with bilirubin 100 µM (61 %) as compared to the untreated control (p < 0.007). Viability decreased significantly with CAM, LCA and UDCA (80 %, 62 % and 27 %, respectively), effects which were abolished by bilirubin. Moreover, bilirubin increased viability in osteoclasts derived from human PBMCs (p < 0.03). Caspase-3 decreased by 46 % with bilirubin 50 µM and increased 10-fold with LCA 100 µM and CAM (p < 0.01). Bilirubin increased miR-21 and miR-148a expression as compared to controls (115 % and 59 %, respectively; p < 0.007). In conclusion, bilirubin increases viability and decreases apoptosis of osteoclasts, and overexpresses the osteoclastogenic miR-21 and miR-148a. The effects of bilirubin counteract the actions of LCA and UDCA. Therefore, bilirubin may contribute to the increased bone resorption and to the development of osteoporosis in advanced liver diseases.
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Resorción Ósea , Hepatopatías , MicroARNs , Osteoporosis , Apoptosis , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/farmacología , Bilirrubina/metabolismo , Bilirrubina/farmacología , Resorción Ósea/metabolismo , Caspasa 3/metabolismo , Diferenciación Celular , Humanos , Hepatopatías/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteoclastos/metabolismo , Osteoporosis/genética , Ligando RANK/metabolismoRESUMEN
INTRODUCTION: Head and neck cancer patients are a population at permanent nutritional risk. In addition to the presence of the tumour, the reason for this is the tumour's location, which affects all structures involved in the swallowing process. The side effects of the oncological treatments they must receive during the course of their illness-surgery, chemo-radiotherapy, etc.-only further burden an already precarious nutritional status. For all these reasons, it is essential that, from the diagnosis of their disease, a multidisciplinary team including specialists in dietetics and nutrition supervises them.
INTRODUCCIÓN: Los enfermos con cáncer de cabeza y cuello son una población en riesgo nutricional permanente. El motivo es, además de la presencia del tumor, la localización del mismo, que afecta a todas las estructuras implicadas en la deglución. Los efectos secundarios de los tratamientos oncológicos que deben recibir en el transcurso de su enfermedad cirugía, quimio-radioterapia, etc. no hacen sino gravar más aun un estado nutricional ya de por sí precario. Por todo ello es imprescindible que, desde el diagnóstico de su enfermedad, estén supervisados por un equipo multidisciplinar con especialistas en dietética y nutrición.
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Dietética , Neoplasias de Cabeza y Cuello , Deglución , Nutrición Enteral , Neoplasias de Cabeza y Cuello/terapia , Humanos , Estado NutricionalRESUMEN
BACKGROUND AND OBJECTIVE: The objective of this project was to adapt to our setting following a systematic process based on the ADAPTE method the first clinical practice guidelines on X-linked hypophosphatemia (XLH) that were published in 2019. MATERIALS AND METHODS: The adaptation of the guidelines to our application and implementation setting was carried out in three phases -start-up, adaptation, and finalization- by a group of experts involved in the management of patients with XLH. RESULTS: Following the original guide, the recommendations agreed by the group that elaborated the guidelines for diagnosis, frequency and scope of visits and specific follow-up in children and adults are presented. On the other hand, recommendations are established for both age groups with conventional treatment, as well as with burosumab in children or adults and those related to the controversial use of growth hormone in children. Suggestions are also proposed regarding the monitoring and management of musculoskeletal disorders and orthopedic treatment in children, dental health and hearing, and neurosurgical complications. Finally, a series of questions and areas are raised in order to deepen the possible future investigation. CONCLUSIONS: These recommendations constitute the systematic adaptation to our setting of the first evidence-based clinical practice guide for the diagnosis and management of XLH and we hope that they can contribute to the adequate management of the disease.
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Raquitismo Hipofosfatémico Familiar , Hipofosfatemia , Adulto , Niño , Consenso , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/terapia , Factores de Crecimiento de Fibroblastos , HumanosAsunto(s)
Fracturas Óseas , Fracturas por Estrés , Osteoporosis , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/etiología , Humanos , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Esternón/diagnóstico por imagenRESUMEN
Increases in bone mineral density (BMD) with osteoporosis treatment are associated with reduced fracture risk. Increasing BMD is therefore a goal of osteoporosis therapy. Here, we compare the probability of achieving a T-score of > -2.5 over 3 years at the total hip (TH) or lumbar spine (LS) in women with osteoporosis, ≥55 years of age, after the following treatment sequences: 1 year romosozumab followed by 2 years denosumab (FRAME and FRAME extension trials), 1 year romosozumab followed by 2 years alendronate, or alendronate-only for 3 years (ARCH trial). Probabilities of attaining the BMD target within 1 year of treatment were also determined. At both skeletal sites, in women with a baseline Tscore ≥ -2.7, there was >50% probability of achieving the BMD target with any 3-year regimen. The probability of achieving the target BMD in those with a baseline TH Tscore equal to -3.0 was 61% with romosozumab/denosumab, 38% with romosozumab/alendronate, and 9% with alendronate. In those with a baseline LS Tscore equal to -3.0, the probability of achieving a T-score > -2.5 was 93% with romosozumab/denosumab, 81% with romosozumab/alendronate, and 55% with alendronate. With 1 year of treatment, in patients with a baseline TH T-score equal to -2.7, the probability of reaching the target Tscore with romosozumab was 71% to 78% and 38% with alendronate. For patients with an initial LS T-score equal to -3.0, the probability of achieving the target T-score over 1 year was 85% to 86% with romosozumab and 25% for alendronate. Our findings suggest baseline BMD and the probability of achieving BMD T-score goals are factors to consider when selecting initial treatment for patients with osteoporosis. As baseline T-score falls below -2.7 (TH) and -3.0 (LS), alendronate has <50% likelihood of achieving a BMD goal above osteoporosis range, whereas these probabilities remain relatively high for regimens beginning with romosozumab. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Fracturas Óseas , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Densidad Ósea , Fracturas Óseas/epidemiología , Humanos , Fracturas Osteoporóticas/epidemiología , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Columna VertebralRESUMEN
The main well recognized action of bisphosphonates (BPs) is their antiresorptive capacity, making them first-line drugs in the treatment of osteoporosis and other metabolic bone diseases. In this review we have compiled other possible actions of BPs, particularly in the areas of immunomodulation, anti-inflammatory capacity and in the prevention of structural joint damage in inflammatory rheumatic diseases. The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). In relation to their anti-inflammatory capacity, special attention has been given to their effect on preventing structural damage in inflammatory joint diseases and on the differential immune response in bone lesions of the most common and representative inflammatory rheumatic diseases, i.e. rheumatoid arthritis and spondyloarthropathies. The present data indicate that more studies are needed to improve the knowledge on the effect of BPs on inflammatory-mediated diseases and particularly on the prevention and/or treatment of the structural damage in these disorders, since these agents could be a potential useful concomitant therapy.
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Artritis Reumatoide , Osteoporosis , Enfermedades Reumáticas , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Citocinas , Difosfonatos/uso terapéutico , Humanos , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of this study was to identify the risk factors associated with fragility fracture (FF) development in glucocorticoid (GC)-treated patients. METHODS: 127 patients (aged 62±18 years, 63% women) on GC-treatment (mean dose 14.5±14.1 mg/day and duration 47.7±69 months) were included. The clinical data collected included bone metabolism study (including gonadal axis), GC-treatment, disease activity, dual-energy X-ray absorptiometry analysis (evaluating densitometric osteoporosis (OP) and trabecular bone score (TBS) degraded microarchitecture values (DMA)), X-ray (assessing vertebral fractures (VF)), FRAX risk (GC-adjusted) and previous FF. RESULTS: 17% of the patients had VF, 28% FF (VF and/or non-VF), 29% OP and 52% DMA. Patients with VF received more GC boluses (57.1% vs 29.5%, p=0.03), were older (68±13 vs 60±19 years, p=0.02), postmenopausal (100% vs 67%, p=0.02), had low testosterone levels (57% vs 11%, p=0.02), lower TBS values (1.119±0.03 vs 1.237±0.013, p<0.001) and higher FRAX risk (17.2±16 vs 9.3±7.6, p=0.003). Patients with FF showed higher accumulated GC doses (16.6±18.4 vs 11.1±12.9 g, p=0.046). On multivariate analysis, hypogonadism (OR 12.38; 95% CI 1.85 to >100, p=0.01) and having received GC boluses (OR 3.45; 95% CI 1.04 to 12.15, p=0.01) were the main factors related to VF. Hypogonadism (OR 7.03; 95% CI 1.47 to 38.37, p=0.01) and FRAX >20 (OR 7.08; 95% CI 1.28 to 53.71, p=0.02) were factors related to FF. CONCLUSION: Hypogonadism is the principal risk factor for developing fractures in GC-treated men and women, whereas receiving GC boluses is a major factor for VF. These results indicate the importance of evaluating the gonadal axis in these patients.
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Susceptibilidad a Enfermedades , Glucocorticoides/efectos adversos , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Absorciometría de Fotón , Adolescente , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Biomarcadores , Densidad Ósea , Estudios Transversales , Femenino , Glucocorticoides/administración & dosificación , Humanos , Hipogonadismo/complicaciones , Hipogonadismo/diagnóstico , Hipogonadismo/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/tratamiento farmacológico , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Fracturas de la Columna Vertebral/diagnóstico , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Osteoporosis is a common complication in patients with primary biliary cholangitis. Both bilirubin and lithocholic acid (LCA) result in detrimental effects on osteoblastic cells, and ursodeoxycholic acid (UDCA) counteracts these outcomes. However, there is no information on the consequences of these retained substances of cholestasis and sera from cholestatic patients in osteocytes. METHODS: The impact of bilirubin, LCA, UDCA and serum from jaundiced patients on viability, differentiation, mineralization and apoptosis has been assessed in MLO-Y4 and MLO-A5 osteocyte cell lines. Effects on gene expression were assessed in these cells and in human bone fragments. RESULTS: Lithocholic acid 10 µmol/L and bilirubin 50 µmol/L decreased viability in MLO-Y4 and MLO-A5 cells (11% and 53% respectively; P ≤ .01). UDCA alone or combined with LCA or bilirubin increased cell viability. Jaundiced sera decreased cell viability (56%), an effect which was reverted by UDCA. Bilirubin decreased differentiation by 47% in MLO-Y4 (P ≤ .01) and mineralization (87%) after 21 days in MLO-A5 (P ≤ .03). Both bilirubin and LCA increased apoptosis in MLO-Y4, and UDCA diminished the apoptotic effect. Moreover, bilirubin down-regulated RUNX2 and up-regulated RANKL gene expression in bone tissue, MLO-Y4 and MLO-A5 cells, and LCA up-regulated RANKL expression in bone tissue. UDCA 100 µmol/L increased the gene expression of all these genes in bone tissue and MLO-Y4 cells and neutralized the decreased RUNX2 expression induced by bilirubin. CONCLUSION: Bilirubin and LCA have damaging consequences in osteocytes by decreasing viability, differentiation and mineralization, increasing apoptosis and modifying gene expression, effects that are neutralized by UDCA.
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Colestasis , Osteoporosis , Ácidos y Sales Biliares , Bilirrubina , Huesos , Humanos , OsteocitosRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory disease that can cause joint destruction and marked disability. Early treatment with disease-modifying drugs, including biological therapy, is the principal treatment to prevent the structural damage associated with this entity. Some studies have indicated that concomitant treatment with antiresorptives, such as bisphosphonates or denosumab, could prevent erosive lesions in this process, and it has even been suggested that treatment with a bone forming agent, such as teriparatide, could revert previously established erosive lesions. In this article we review the evidence available on the efficacy of treatment with antiresorptives and bone forming agents in the prevention and/or treatment of bone erosions associated with RA.