Effect of gender on the evolution of pain and quality of life after treatment of symptomatic vertebral fragility fractures.

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.

Impacto de las fracturas por fragilidad en mujeres españolas con osteoporosis posmenopáusica / Impact of fragility fractures in postmenopausal Spanish women with osteoporosis

Objetivo: dada la repercusión que tienen las fracturas por fragilidad y sus secuelas en la vida de las mujeres con osteoporosis posmenopáusica (OPM), el objetivo de este estudio es describir y analizar su impacto en esta población. Material y métodos: se realizó una encuesta a mujeres posmenopáusicas con fractura por fragilidad en un diseño observacional transversal. Se recogieron variables sociodemográficas, impacto de la fractura (necesidad de cuidados, productividad laboral), calidad de vida relacionada con la salud (CVRS, mediante cuestionario QUALEFFO-31) y disposición a pagar (DAP) por recuperarla. Resultados: participaron 120 mujeres, promedio de edad 62 ± 7 años. Las fracturas más frecuentes fueron las de radio distal (29,9 %) y las vertebrales (21,3 %). Un 53,3 % necesitó cuidados durante su recuperación (76,5 % informales; 24,9 % formales) y un 4,2 % tuvo que ingresar en un centro/residencia sociosanitaria. De aquellas que trabajaban cuando se produjo la fractura (62,5 %), el 56 % vio su vida laboral afectada (69,3 % incapacidad temporal; 17,3 % incapacidad permanente; 10,7 % reducción de jornada; 10,7 % abandono laboral; 5,3 % permiso/excedencia; 3,6 % prejubilación). El impacto de la fractura se debió principalmente al dolor (71,7 %), dificultad para realizar actividades cotidianas (48,3 %), problemas de movilidad (46,7 %) y estado emocional (41,7 %). La mayor DAP se ofreció por recuperar la capacidad para realizar actividades cotidianas y el estado emocional. La puntuación total QUALEFFO-31 (0-100) fue 49,9 ± 10,8 (función mental: 68,3 ± 7,3; dolor: 56 ± 22,6; función física: 39,3 ± 15,5). Conclusiones: las fracturas por fragilidad tienen un alto impacto en la calidad de vida de las mujeres con OPM. Resulta fundamental poner en valor aquellos aspectos que más les preocupan para optimizar su abordaje. (AU)

Objective: Given the impact of fragility fractures and their consequences on the lives of women with postmenopausal osteoporosis (PMO), the objective of this study is to describe and analyze the impact of this kind of fractures on this population. Materials and methods: A survey was conducted among postmenopausal women with fragility fractures in a cross-sectional observational design. Sociodemographic variables, fracture impact (need for care, work productivity), and data on health-related quality of life (HRQoL, assessed using the QUALEFFO-31 questionnaire), and willingness to pay (WTP) to regain HRQoL were collected. Results: A total of 120 women participated, with a mean age of 62 ± 7 years. The most frequent fractures described were distal radius fractures (29.9 %), followed by vertebral fractures (21.3 %). A total of 53.3 % required care during their recovery (76.5 %, informal; 24.9 %, formal), and 4.2 % had to be admitted to a health care or nursing home. Among those who were working when the fracture occurred (62.5 %), 56 % had their working life affected (69.3 %, temporary disability; 17.3 %, permanent disability; 10.7 %, reduced working hours; 10.7 %, quit their jobs; 5.3 %, leave of absence; and 3.6 %, early retirement). The impact of the fracture was primarily due to pain (71.7 %), difficulty performing activities of daily living (48.3 %), mobility problems (46.7 %), and emotional state (41.7 %). The highest WTP was offered to regain the ability to perform activities of daily living and improve the emotional state. The overall QUALEFFO-31 score (0-100) was 49.9 ± 10.8 (mental function, 68.3 ± 7.3; pain, 56 ± 22.6; physical function, 39.3 ± 15.5). Conclusions: Fragility fractures play a significant role on the quality of life of women with PMO. It is of paramount importance to value the aspects that concern them the most to optimize their management. (AU)

Osteoclast generation from RAW 264.7 and PBMC cells. The set up in our lab / Generación de osteoclastos a partir de células RAW 264.7 y PBMC. El montaje en nuestro laboratorio

Introduction and objectives: osteoclasts are terminally differentiated giant multinucleated cells derived from the fusionof mononuclear progenitors of the monocyte/macrophage hematopoietic lineage. The objective of our group was to achie-ve the best method for osteoclast differentiation, from both RAW 264.7 cells and peripheral blood monocytes.Material and methods: RAW 264.7 cells and human PBMCs were differentiated into osteoclasts. Success in differentiationwas assessed by TRAP staining. Osteoclast activity was detected by the resorption pits in Corning® Osteo Assay SurfacePlates.Results: the optimal cell density for RAW 264.7 cell differentiation was 25,000 cells/cm2 with 30 ng/mL of RANKL for6 days. Osteoclasts differentiated from PBMCs were observed after 4 weeks with 25 ng/mL M-CSF and 30 ng/mL RANKL.Individual pits or multiple pit clusters were observed on the surface plates.Conclusions: we report optimal conditions for the differentiation of osteoclasts from.(AU)

Osteomalacia hipofosfatémica ligada al cromosoma X (XLH): análisis de 5 pacientes adultos / X-linked hypophosphatemic osteomalacia (XLH): Study of 5 adult patients

Antecedentes: La osteomalacia hipofosfatémica ligada al cromosoma X (XLH) es un trastorno hereditario que puede ocasionar comorbilidades musculoesqueléticas altamente incapacitantes en edad adulta.ObjetivoAnalizar las características clínico-radiológicas, comorbilidades y complicaciones asociadas a la enfermedad y al tratamiento en la población adulta con XLH.MétodoEstudio retrospectivo de pacientes atendidos por XLH en un servicio de reumatología los últimos 10 años, evaluando los hallazgos clínico-radiológicos, las comorbilidades y las complicaciones asociadas.ResultadosSe incluyeron 5 pacientes de entre 39 y 75 años de edad. Todos presentaban talla baja, síntomas osteoarticulares y entesopatía radiológica. En 4 se observó artropatía degenerativa precoz de rodillas y caderas, y alteraciones dentales asociadas a su enfermedad. Todos los pacientes mayores de 50 años requirieron algún tipo de sustitución protésica. Dos pacientes presentaron fracturas de estrés en fémur, uno litiasis renal y otro desarrolló un hiperparatiroidismo terciario.ConclusionesLas manifestaciones musculoesqueléticas son frecuentes e invalidantes en la población adulta con XLH, por lo que un adecuado diagnóstico y manejo desde la infancia son esenciales para prevenir el desarrollo de complicaciones en la edad adulta asociadas a esta enfermedad. (AU)

Background: X-linked hypophosphatemic osteomalacia (XLH) is an inherited disorder that can cause highly disabling musculoskeletal comorbidities in adulthood.ObjectiveTo analyze the clinical-radiological characteristics, comorbidities and complications associated with the disease and treatment in an adult population with XLH.MethodRetrospective study of patients treated for XLH in a rheumatology department in the last 10 years, evaluating the clinical-radiological findings, comorbidities and associated complications.ResultsFive 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.ConclusionsMusculoskeletal 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. (AU)

[X-linked hypophosphatemic osteomalacia (XLH): Study of 5 adult patients]. / Osteomalacia hipofosfatémica ligada al cromosoma X (XLH): análisis de 5 pacientes adultos.

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.

Osteoporosis related to WNT1 variants: a not infrequent cause of osteoporosis.

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.

Effect of moderate beer consumption (with and without ethanol) on osteoporosis in early postmenopausal women: Results of a pilot parallel clinical trial.

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.

Recomendaciones de práctica clínica para el diagnóstico y el tratamiento de la hipofosfatemia ligada al cromosoma X: un consenso basado en el método ADAPTE / Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method

Antecedentes y objetivoEl objetivo de este proyecto fue adaptar la primera guía de práctica clínica en la hipofosfatemia ligada al cromosoma X (XLH) aparecida en 2019 a nuestro medio siguiendo un proceso sistemático basado en el método ADAPTE.Materiales y métodosLa adaptación de las guías a nuestro ámbito de aplicación e implementación se llevó a cabo en 3 fases —puesta en marcha, adaptación y finalización— mediante un grupo de expertos implicados en el manejo de los pacientes con XLH.ResultadosSiguiendo la guía original, se presentan las recomendaciones acordadas por el grupo elaborador de las guías para el diagnóstico, la frecuencia y el ámbito de las visitas y el seguimiento específico en niños y adultos. Por otro lado, se establecen las recomendaciones para ambas franjas de edad con tratamiento convencional, así como con burosumab en niños o adultos y las relacionadas al controvertido uso de hormona de crecimiento en niños. También se proponen sugerencias en cuanto al seguimiento y al manejo de las alteraciones del aparato locomotor y tratamiento ortopédico en niños, la salud dental y la audición y las complicaciones neuroquirúrgicas. Por último, se plantean una serie de cuestiones y áreas en las que profundizar en una posible investigación futura.ConclusionesEstas recomendaciones constituyen la adaptación sistemática a nuestro medio de la primera guía de práctica clínica basada en la evidencia para el diagnóstico y el manejo de la XLH, y esperamos que pueda contribuir al manejo adecuado de la enfermedad. (AU)

Background and objectiveThe 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 methodsThe 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.ResultsFollowing 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.ConclusionsThese 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. (AU)

Bilirubin increases viability and decreases osteoclast apoptosis contributing to osteoporosis in advanced liver diseases.

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.

Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method. / Recomendaciones de práctica clínica para el diagnóstico y el tratamiento de la hipofosfatemia ligada al cromosoma X: un consenso basado en el método ADAPTE.

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.

[12th "Jesús Culebras" Lesson. Feeding and nutrition in patients with head and neck cancer - A permanent challenge]. / 12.ª Lección Jesús Culebras. La alimentación y la nutrición en los enfermos con cáncer de cabeza y cuello: un reto permanente.

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.

Romosozumab Followed by Antiresorptive Treatment Increases the Probability of Achieving Bone Mineral Density Treatment Goals.

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.

Bisphosphonates in inflammatory rheumatic diseases.

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.