Prevention and early diagnosis of childhood osteoporosis : Are we doing the right thing?

To assess prevention, early diagnosis and training received regarding osteoporosis among the pediatrics professionals in our area. Survey directed to physicians of pediatricians of Primary Care (PC) and Specialized Care (SC) in order to evaluate their activity in prevention, detection and training received in osteoporosis. The survey was disseminated through the relevant scientific societies. 420 pediatricians participated (324 from PC and 96 from SC). 93.5% of PC pediatricians and 89.6% of SC pediatricians valued the physical activity of the patients; 85.19% and 35.4% of them, respectively, the intake of dairy products. 45.68% of PC and 70.2% of SC recommended calcium and vitamin D supplements in the case of low nutritional intake, whereas 39.2% of PC and 47.2% of SC favored follow-up. 39.6% of SC pediatricians requested bone densitometry for this disease or risk treatment, and 47.9% measured the levels of 25-OH-vitamin D. 25.93% of PC and 45.3% of SC asked about the existence of fractures, 90.4% and 96.8% requested etiopathogenic mechanism. 40% of PC and 86.2% of SC requested a bone densitometry or referred to the specialist for fractures due to low trauma energy, with specific criteria in 13.7% and 5.86%, respectively. 92% of PC and 82.3% of SC had not received recent training in childhood osteoporosis. Detection, derivation circuits and the training of pediatricians regarding bone health in our country can be improved. Optimizing these aspects is essential to favor the peak of bone mass in our population

Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children

Background: Osteoporosis incidence in children is increasing due to the increased survival rate of patients suffering from chronic diseases and the increased use of drugs that can damage bones. Recent changes made to the definition of childhood osteoporosis, along with the lack of guidelines or national consensuses regarding its diagnosis and treatment, have resulted in a wide variability in the approaches used to treat this disease. For these reasons, the Osteogenesis Imperfecta and Childhood Osteoporosis Working Group of the Spanish Society of Pediatric Rheumatology has sounded the need for developing guidelines to standardize clinical practice with regard to this pathology. Methods: An expert panel comprised of 6 pediatricians and 5 rheumatologists carried out a qualitative literature review and provided recommendations based on evidence, when that was available, or on their own experience. The level of evidence was determined for each section using the Oxford Centre for Evidence-based Medicine (CEBM) system. A Delphi survey was conducted for those recommendations with an evidence level of IV or V. This survey was sent to all members of the SERPE. All recommendations that had a level of agreement higher or equal to 70% were included. Results: Fifty-one recommendations, categorized into eight sections, were obtained. Twenty-four of them presented an evidence level 4 or 5, and therefore a Delphi survey was conducted. This was submitted electronically and received a response rate of 40%. All recommendations submitted to the Delphi round obtained a level of agreement of 70% or higher and were therefore accepted. Conclusion: In summary, we present herein guidelines for the prevention, diagnosis and treatment of secondary childhood osteoporosis based on the available evidence and expert clinical experience. We believe it can serve as a useful tool that will contribute to the standardization of clinical practice for this pathology. Prophylactic measures, early diagnosis and a proper therapeutic approach are essential to improving bone health, not only in children and adolescents, but also in the adults they will become in the future

Estudio de fragilidad ósea en población pediátrica con factores de riesgo

La presente tesis doctoral aborda el problema de la Baja Masa Ósea para la edad cronológica (BMOec) y la Osteoporosis infantil (OPi), situaciones que pueden ser silentes y que requieren de una investigación activa para llegar a su diagnóstico en edad pediátrica. El objetivo principal de esta tesis es estimar la prevalencia de dichas enfermedades en los pacientes con riesgo de presentarlas, así como evaluar las características densitométricas de los mismos, tanto la cantidad ósea mediante Densidad Mineral Ósea, como la calidad ósea mediante Trabecular Bone Score. Los objetivos secundarios han sido describir las características clínicas de esta población y comparar los hallazgos densitométricos con los de población sana sin factores de riesgo. Se incluyeron 103 pacientes con edades comprendidas entre los 2 y los 20 años de edad. Todos ellos con al menos un factor de riesgo: entre los más prevalentes la presencia de un diagnóstico potencialmente osteopenizante y la ingesta inadecuada de calcio. Entre el 6 y el 10% de la muestra presentaba BMOec, que variaba según la región de interés estudiada y el ajuste de talla. Cinco sujetos presentaban criterios de OPi por presencia de fracturas vertebrales, en 4 de ellos las fracturas fueron silentes y descubiertas mediante técnicas de imagen. TBS resultó inferior en los sujetos con BMOec medida en cuerpo entero. La DMO de adolescentes y jóvenes fue menor en población con factores de riesgo frente a la población sana de la misma edad y género. TBS fue menor en adolescentes y jóvenes femeninas pero mayor en el resto de grupos estudiados.This doctoral thesis deals with Low Bone Mass for chronological age (LBMca) and infantile Osteoporosis (iOP), both can be asymptomatic and may require an extra effort to get to their diagnosis in pediatric age. The main objective of this work is to estimate the prevalence of these diseases in patients at risk of presenting them, as well as to evaluate these patient’s densitometric characteristics, both quantity through Bone Mineral Density, and quality through Trabecular Bone Score. Secondary objectives include the description of the clinical characteristics of our sample, as well as the comparison of the densitometric findings with those of healthy peers without risk factors. We included 103 patients aged between 2 and 20 years of age. All of them with at least one risk factor. The presence of a potentially osteopening diagnosis and the inadequate calcium intake that did not reach the daily recommendations were the most prevalent risks factors. Between 6 and 10% of the sample presented LBMca, which varied according to the regions of interest studied and the height adjustment. 5 subjects met iOP criteria for the presence of vertebral fractures. In 4 of them, these fractures were silent and were localized by imaging techniques. TBS was lower in subjects with LBMca measured in the whole body region. Adolescents and young people BMD was lower in the population with risk factors compared to the healthy population of the same age and gender. TBS was lower in adolescents and young women but higher in the rest of the groups

Estudio de fragilidad ósea en población pediátrica con factores de riesgo

La presente tesis doctoral aborda el problema de la Baja Masa Ósea para la edad cronológica (BMOec) y la Osteoporosis infantil (OPi), situaciones que pueden ser silentes y que requieren de una investigación activa para llegar a su diagnóstico en edad pediátrica. El objetivo principal de esta tesis es estimar la prevalencia de dichas enfermedades en los pacientes con riesgo de presentarlas, así como evaluar las características densitométricas de los mismos, tanto la cantidad ósea mediante Densidad Mineral Ósea, como la calidad ósea mediante Trabecular Bone Score. Los objetivos secundarios han sido describir las características clínicas de esta población y comparar los hallazgos densitométricos con los de población sana sin factores de riesgo. Se incluyeron 103 pacientes con edades comprendidas entre los 2 y los 20 años de edad. Todos ellos con al menos un factor de riesgo: entre los más prevalentes la presencia de un diagnóstico potencialmente osteopenizante y la ingesta inadecuada de calcio. Entre el 6 y el 10% de la muestra presentaba BMOec, que variaba según la región de interés estudiada y el ajuste de talla. Cinco sujetos presentaban criterios de OPi por presencia de fracturas vertebrales, en 4 de ellos las fracturas fueron silentes y descubiertas mediante técnicas de imagen. TBS resultó inferior en los sujetos con BMOec medida en cuerpo entero. La DMO de adolescentes y jóvenes fue menor en población con factores de riesgo frente a la población sana de la misma edad y género. TBS fue menor en adolescentes y jóvenes femeninas pero mayor en el resto de grupos estudiados.This doctoral thesis deals with Low Bone Mass for chronological age (LBMca) and infantile Osteoporosis (iOP), both can be asymptomatic and may require an extra effort to get to their diagnosis in pediatric age. The main objective of this work is to estimate the prevalence of these diseases in patients at risk of presenting them, as well as to evaluate these patient’s densitometric characteristics, both quantity through Bone Mineral Density, and quality through Trabecular Bone Score. Secondary objectives include the description of the clinical characteristics of our sample, as well as the comparison of the densitometric findings with those of healthy peers without risk factors. We included 103 patients aged between 2 and 20 years of age. All of them with at least one risk factor. The presence of a potentially osteopening diagnosis and the inadequate calcium intake that did not reach the daily recommendations were the most prevalent risks factors. Between 6 and 10% of the sample presented LBMca, which varied according to the regions of interest studied and the height adjustment. 5 subjects met iOP criteria for the presence of vertebral fractures. In 4 of them, these fractures were silent and were localized by imaging techniques. TBS was lower in subjects with LBMca measured in the whole body region. Adolescents and young people BMD was lower in the population with risk factors compared to the healthy population of the same age and gender. TBS was lower in adolescents and young women but higher in the rest of the groups

Estudio de fragilidad ósea en población pediátrica con factores de riesgo /

La presente tesis doctoral aborda el problema de la Baja Masa Ósea para la edad cronológica (BMOec) y la Osteoporosis infantil (OPi), situaciones que pueden ser silentes y que requieren de una investigación activa para llegar a su diagnóstico en edad pediátrica. El objetivo principal de esta tesis es estimar la prevalencia de dichas enfermedades en los pacientes con riesgo de presentarlas, así como evaluar las características densitométricas de los mismos, tanto la cantidad ósea mediante Densidad Mineral Ósea, como la calidad ósea mediante Trabecular Bone Score. Los objetivos secundarios han sido describir las características clínicas de esta población y comparar los hallazgos densitométricos con los de población sana sin factores de riesgo. Se incluyeron 103 pacientes con edades comprendidas entre los 2 y los 20 años de edad. Todos ellos con al menos un factor de riesgo: entre los más prevalentes la presencia de un diagnóstico potencialmente osteopenizante y la ingesta inadecuada de calcio. Entre el 6 y el 10% de la muestra presentaba BMOec, que variaba según la región de interés estudiada y el ajuste de talla. Cinco sujetos presentaban criterios de OPi por presencia de fracturas vertebrales, en 4 de ellos las fracturas fueron silentes y descubiertas mediante técnicas de imagen. TBS resultó inferior en los sujetos con BMOec medida en cuerpo entero. La DMO de adolescentes y jóvenes fue menor en población con factores de riesgo frente a la población sana de la misma edad y género. TBS fue menor en adolescentes y jóvenes femeninas pero mayor en el resto de grupos estudiados.This doctoral thesis deals with Low Bone Mass for chronological age (LBMca) and infantile Osteoporosis (iOP), both can be asymptomatic and may require an extra effort to get to their diagnosis in pediatric age. The main objective of this work is to estimate the prevalence of these diseases in patients at risk of presenting them, as well as to evaluate these patient's densitometric characteristics, both quantity through Bone Mineral Density, and quality through Trabecular Bone Score. Secondary objectives include the description of the clinical characteristics of our sample, as well as the comparison of the densitometric findings with those of healthy peers without risk factors. We included 103 patients aged between 2 and 20 years of age. All of them with at least one risk factor. The presence of a potentially osteopening diagnosis and the inadequate calcium intake that did not reach the daily recommendations were the most prevalent risks factors. Between 6 and 10% of the sample presented LBMca, which varied according to the regions of interest studied and the height adjustment. 5 subjects met iOP criteria for the presence of vertebral fractures. In 4 of them, these fractures were silent and were localized by imaging techniques. TBS was lower in subjects with LBMca measured in the whole body region. Adolescents and young people BMD was lower in the population with risk factors compared to the healthy population of the same age and gender. TBS was lower in adolescents and young women but higher in the rest of the groups

Effectiveness and safety of bisphosphonates therapy in secondary osteoporosis in children Efectividad y seguridad de los bisfosfonatos en el tratamiento de la osteoporosis infantil secundaria

Introduction: There are few studies on effectiveness and safety of bisphosphonate therapy in secondary osteoporosis in children. The aim of this research was to analyse effectiveness and safety of bisphosphonates in secondary osteoporosis in children. Patients and methods: Multicentre retrospective study in patients younger than 18 suffering from secondary osteoporosis and who had received bisphosphonates. Clinical data were recorded. Bone mineral density was assessed in terms of bone mineral density Z-score in lumbar spine (ZBMDls) measured by dual-energy X-ray absorptiometry (DXA). Effectiveness was valued at changes in ZBMDls one and two years after the onset of bisphosphonates and at the decrease in the number of fractures a year. Adverse events reported were recorded. Descriptive and bivariant analysis were performed. Results: 32 patients were recruited. ZBMDls increased one year after the onset of treatment ([−2.46 ± 0.96] vs. [−1.54 ± 1.38]; p <.001). Fractures a year decreased significantly (1 [1-2] vs. 0 [0-0.61]; p <, 001). ZBMDls increase was higher in patients who were able to walk (1.88 ± 0.72 vs. 0.55 ± 0.82; p =.07) and correlated positively with body mass index (BMI) for age percentile (rho: 0.564; p <.001). The decrease in the number of fractures a year was higher in patients with lower initial fracture rate (rho: −0.47; p =.006) and with higher initial ZBMDls (rho: −0.47; p =.07). 10 adverse events were reported in 7 patients (22%), all of them intravenous bisphosphonates related. No association was found between adverse events and studied variables. Conclusions: Bisphosphonates are effective in secondary osteoporosis in children. Response seems to be better in patients who are able to walk, well-nourished and in the early stages of the disease. Adverse events were frequent but mild

Association of platelet binding to lymphocytes with B cell abnormalities and clinical manifestations in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome : a 3-year follow-up cohort study

This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren’s syndrome: a 3-year follow-up cohort study

IntroductionThis was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren’s syndrome (SS).MethodsThe inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted.ResultsA total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers.DiscussionPatients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci

Incidence and clinical manifestations of giant cell arteritis in Spain: results of the ARTESER register

Objective This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season.Methods We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season.Results We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80–84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients.Conclusions This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year