Lineamientos para la prevención y el tratamiento de la osteoporosis inducida por glucocorticoides en pediatría / Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in pediatrics

Objetivo. Proporcionar un marco para profesionales de la salud que tratan a pacientes pediátricos bajo terapia con glucocorticoides (GC) y desarrollar recomendaciones para la prevención y el tratamiento de la osteoporosis inducida por GC en la población pediátrica. Métodos. Un panel de expertos en enfermedades óseas y pediátricas generó una serie de preguntas PICO que abordan aspectos relacionados con la prevención y el tratamiento de osteoporosis en pacientes bajo tratamiento con GC. Siguiendo la metodología GRADE, se realizó una revisión sistemática de la literatura, se resumieron las estimaciones del efecto y se calificó la calidad de la evidencia. Luego se procedió a la votación y a la formulación de las recomendaciones. Resultados. Se desarrollaron 7 recomendaciones y 6 principios generales para osteoporosis inducida por GC en población pediátrica. Conclusión. Estas recomendaciones proporcionan orientación para los médicos que deben tomar decisiones en pacientes pediátricos bajo tratamiento con GC.

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC.

Histomorphometry of Bone Microarchitecture in Rats Treated with Vitamin D and Bisphosphonate in the Management of Osteoporosis / Histomorfometria da microarquitetura óssea em ratas tratadas com vitamina D e bisfosfonato no manejo da osteoporose

Abstract Objective To verify how the combined administration of alendronate (ALN) and vitamin D3 (VD) acts on the bone microarchitecture in rats with glucocorticoid-induced osteoporosis. Methods The experiment used 32 90-day-old female Wistar rats weighing between 300 and 400g. The induction of osteoporosis consisted of intramuscular administration of dexamethasone at a dose of 7.5 mg/kg of body weight once a week for 5 weeks, except for the animals in the control group. The animals were separated into the following groups: G1 (control group without osteoporosis), G2 (control group with osteoporosis without treatment), G3 (group with osteoporosis treated with ALN 0.2 mg/kg), G4 (group with osteoporosis treated with VD 10,000UI/500μL), and G5 (group with osteoporosis treated with ALN þ VD). The right femurs of the rats were fixed in 10% buffered formaldehyde, decalcified, and processed for inclusion in paraffin. Histological sections were stained with hematoxylin-eosin for histomorphometric analysis. Cortical thickness and medullary cavity were measured in cross-sections. Results There was a statistical difference (p< 0.05) between groups G3 and G5 compared with the positive control group (G2), both related to the measurement of cortical thickness and to the total diameter of the bone. In the evaluation of the spinal area, only the G3 group has shown to be statistically different from the G2 group. Conclusion Concomitant treatment with daily ALN and weekly VD is effective in preventing glucocorticoid-induced bone loss. However, there was no difference between the therapy tested and treatment with ALN alone.

Resumo Objetivo Verificar como a administração conjunta de alendronato de sódio (ALN) e vitamina D3 (VD) atua na microarquitetura óssea em ratas com osteoporose induzida por glicocorticoide. Métodos O experimento utilizou 32 ratas da linhagem Wistar, com peso médio de 300 a 400g, com 90 dias de vida. A indução da osteoporose consistiu na administração de dexametasona na dose de 7,5 mg/kg de peso corporal, por via intramuscular, 1 vez por semana durante 5 semanas, à exceção dos animais do grupo controle. Os animais foram distribuídos nos seguintes grupos: G1 (grupo controle sem osteoporose), G2 (grupo controle com osteoporose sem tratamento), G3 (grupo com osteoporose tratado com ALN 0,2 mg/kg), G4 (grupo com osteoporose tratado com VD 10.000UI/500μL) e G5 (grupo com osteoporose tratado com ALN þ VD). Os fêmures direitos das ratas foram fixados em formol a 10% tamponado, descalcificados e processados para inclusão em parafina. Os cortes histológicos foram corados com hematoxilina-eosina para análise histomorfométrica. A espessura cortical e a cavidade medular foram medidas em cortes transversais. Resultados Houve diferença estatística (p< 0,05) entre os grupos G3 e G5 em relação ao grupo controle positivo (G2), tanto em relação à medida da espessura cortical quanto em relação ao diâmetro total do osso. Na avaliação da área medular, apenas o grupo G3 se mostrou estatisticamente diferente do grupo G2. Conclusão O tratamento concomitante com ALN diário e VD semanal é eficaz para prevenir a perda óssea induzida por glicocorticoide. No entanto, não houve diferença entre esta terapia testada e o tratamento apenas com o ALN.

Histopathological and immunohistochemical study of antiosteoporotic efficacy of the earthworm Allolobophora caliginosa extract in orchiectomized rats / Estudio histopatológico e inmunohistoquímico de la eficacia antiosteoporótica del extracto de lombriz de tierra Allolobophora caliginosa en ratas orquiectomizadas

SUMMARY: Osteoporosis is a bone condition marked by a loss of bone mass and a disruption of bone microarchitecture. Men lose bone density as they age, resulting in brittle bones. The loss of free testosterone is one of the key factors. The objective of present study was to evaluate Allolobophora caliginosa extract (AcE) for its anti-osteoporotic and antiapoptotic activity in orchiotomized rat model at two different dose levels. Twenty eight male rats were divided into two groups. The first group represented sham operated rats while the second group underwent bilateral orchidectomy (OCX). After one week of recovery from orchidectomy surgery, the second group was randomly subdivided into 3 subgroups. The first OCX subgroup was administered orally distilled water daily for 10 weeks. The other two OCX subgroups were administered AcE (100 or200 mg/kg body weight/day) orally for 10 weeks. Orchiectomy induces remarkable loss of the cortical as well as trabecular bone loss; which, could be counterbalanced by Allolobophora caliginosa extract (AcE) that prevented cortical as well as trabecular bone loss. Allolobophora caliginosa extract (AcE) at Dose 200 mg/kg/day was found to be effective at a highly significant level in osteoporotic bone, as determined by histological images and immunohistochemical study, where Dose (100 mg/kg/day) was found to be moderately significant.In the present study, it is suggested that AcE may inhibit steroid-induced osteoblasts apoptosis, potentially via upregulation of Bcl-2 and downregulation of caspase-3. Allolobophora caliginosa extract demonstrates anti-apoptotic and anti-oxidant properties. Therefore, AcE may be used for the prevention of steroid-induced bone damage.

RESUMEN: La osteoporosis es una afección ósea caracterizada por una pérdida de masa ósea y una alteración de la microarquitectura ósea. Los hombres pierden densidad ósea a medida que envejecen, lo que resulta en huesos quebradizos. La pérdida de testosterona libre es factor clave en este proceso. El objetivo del presente estudio fue evaluar el extracto de Allolobophora caliginosa (AcE) debido a su actividad antiosteoporótica y antiapoptótica en un modelo de rata orquiectomizadas con dos niveles de dosis diferentes. Se dividieron veintiocho ratas macho en dos grupos. El primer grupo incluyó ratas con operación simulada, mientras que el segundo grupo se sometió a orquidectomía bilateral (OCX). Después de una semana de recuperación de la orquidectomía, el segundo grupo fue subdividido en 3 subgrupos. Al primer subgrupo de OCX se administró diariamente agua destilada por vía oral durante 10 semanas. Los otros dos subgrupos de OCX se administraron por vía oral AcE (100 o 200 mg / kg de peso corporal / día) durante 10 semanas. La orquidectomía induce una pérdida notable del hueso cortical y trabecular; el cual podría ser contrarrestado por el extracto de Allolobophora caliginosa (AcE) que previno la pérdida de hueso tanto cortical como trabecular visualizado en imágenes histológicas y estudio inmuno- histoquímico, donde se encontró que la dosis (100 mg / kg / día) era moderadamente significativa. En el presente estudio, se sugiere que la AcE puede inhibir la apoptosis de los osteoblastos inducida por esteroides, potencialmente a través de la regulación al alza de Bcl 2 y la regulación a la baja de caspasa 3. El extracto de Allolobophora caliginosa demuestra propiedades anti apoptóticas y antioxidantes. Por lo tanto, AcE puede usarse para la prevención del daño óseo inducido por esteroides.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model / 中西医结合学报

OBJECTIVE@#In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish.@*METHODS@#The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 μmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio.@*RESULTS@#According to the Chinese Pharmacopoeia (2015), β-ecdysone (β-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of β-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 μmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 μmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and β-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1.@*CONCLUSION@#RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Protective effect of Sika Deer bone polypeptide extract on dexamethasone-induced osteoporosis in rats

BACKGROUND: Osteoporosis attacks approximately 10% of the population worldwide. Sika Deer (Cervus nippon), one of China's precious traditional medicinal animals, has been widely recorded in ancient Chinese medical books and claimed for centuries to have numerous medical benefits including bone strengthening. This study aimed to find the use of Sika Deer bone in treating osteoporosis according to traditional records and to investigate the protective effect of Sika Deer bone polypeptide extract on glucocorticoidinduced osteoporosis (GIOP) in rats. RESULTS: Sika Deer bone polypeptide extract could increase serum Ca2+ and BGP, decrease serum P3+, ALP, PTH, and CT, but had no effect on serum NO in rats with GIOP. The immunohistochemical iNOS results of the rats' distal femur were negative in each group. Besides the model group, the eNOS color reaction in osteoblasts was strongly positive in the other three groups. CONCLUSIONS: Sika Deer bone polypeptide extract can improve pathological changes in the microstructure and stimulate the expression of eNOS in osteoblasts. The protective effect on bone might be mediated by eNOS-dependent NO generation.

Osteoporosis, un problema de salud de estos tiempos / Osteoporosis, a health problem of our times

RESUMEN En los adultos mayores existen múltiples enfermedades que afectan su calidad de vida y el logro de una longevidad satisfactoria. Una de ellas es la osteoporosis, enfermedad de elevada incidencia a nivel mundial, lo cual también se refleja en Cuba. Siendo una afección que conlleva a un alto grado de discapacidad, constituye un problema en el campo de la salud y de magnitud epidémica, más aún cuando la supervivencia de la humanidad tiende al aumento. Con el objetivo de estructurar los referentes teóricos sobre la osteoporosis, que contribuyan a la capacitación de médicos y estudiantes de Medicina como promotores de salud en prevención primaria de esta enfermedad, se realizó el siguiente artículo científico. Los factores que predisponen la aparición de la enfermedad son diversos, algunos modificables. Se señaló la importancia de su prevención, diagnóstico y tratamiento, así como formas de actuar sobre la misma, para modificar estilos de vida en la comunidad (AU).

ABSTRACT There are many diseases affecting life quality and the achievement of a satisfactory longevity in elder people; osteoporosis, a disease of high incidence around the world that also strikes in Cuba, is found among them. It is an affection leading to a high disability level, being a problem in the health field with an epidemic magnitude, even more when the human kind survival tends to increase. The current scientific article was written with the objective of structuring the theoretical referents on osteoporosis contributing to train Medicine doctors and students as health promoters in the primary prevention of this disease. The factors predisposing the disease's appearance are different, some of them modifiable. It is also stated the importance of its prevention, diagnosis and treatment, and also forms and ways of working on it to modify life styles in the community (AU).

VIH y salud ósea / HIV and bone health

Con el advenimiento de la terapia antirretroviral, el pronóstico y la sobrevida de los pacientes infectados con el virus de la inmunodeficiencia humana (VIH) han cambiado de manera radical, por lo cual en la actualidad se evidencia un aumento en el riesgo de padecer enfermedades no relacionadas con el VIH como, por ejemplo, la osteoporosis. La disminución de la densidad mineral ósea (DMO) se observa en el 40-90% de las personas infectadas por el VIH, con una prevalencia de osteopenia y osteoporosis del 52 y 15%, respectivamente. Esta población de pacientes tiene un mayor riesgo de fracturas (60%) en comparación con personas no infectadas y un riesgo de fracturas vertebrales 2,3 veces mayor que en la población general. El tenofovir fumarato se asoció con un aumento de pérdida renal de fósforo e hiperparatiroidismo secundario. El efavirenz y los inhibidores de proteasas (IP) afectan el metabolismo de la vitamina D; actúan a nivel enzimático aumentando la expresión de la enzima CYP24 que lleva a producción de vitamina D inactiva. El FRAX es una herramienta sencilla y accesible, por lo que su uso está recomendado en pacientes con VIH. Además de las medidas higiénico-dietéticas, actividad física, calcio y vitamina D, el uso de bifosfonatos está indicado en el tratamiento de la osteoporosis en estos pacientes. (AU)

With the advent of antiretroviral therapy, the prognosis and survival of patients infected with the human immunodeficiency virus (HIV) have radically changed, which is why there is now evidence of an increased risk of suffering from diseases not related to HIV such as osteoporosis. The decrease in bone mineral density (BMD) is observed in 40-90% of people infected with HIV, with a prevalence of osteopenia and osteoporosis of 52 and 15%, respectively. This patient population has a 60% higher risk of fractures compared to uninfected people and a risk of vertebral fractures 2.3 times higher than in the general population. Tenofovir fumarate administration is associated with increased renal phosphorus loss and secondary hyperparathyroidism. Efavirenz and protease inhibitors (IP) affect the metabolism of vitamin D, they act at the enzymatic level by increasing the expression of the CYP24 enzyme that leads to the production of inactive vitamin D. The FRAX is a simple and accessible tool, so its use is recommended in patients with HIV and in addition to dietary hygiene measures, physical activity, calcium, and vitamin D, the use of bisphosphonates is indicated in the treatment of osteoporosis in these patients. (AU)

Análise do fêmur de ratas tratadas com ocitocina e submetidas ao treinamento de força durante a periestropausa / Analysis of the femur of rats treated with oxytocin and submitted to strength training during periestropause

A diminuição nas concentrações de estrógeno, como o que ocorre no período da perimenopausa e menopausa, contribui para o aumento do turnover ósseo, com taxa de reabsorção superior à de formação óssea que favorece a instalação da osteoporose, doença silenciosa que determina fragilidade óssea e maior probabilidade de fraturas. Entre as intervenções utilizadas para prevenção da osteoporose, destaca-se o treinamento de força (TF) e a ocitocina (OT), hormônio promissor com ação anabólica no osso. O objetivo deste estudo foi verificar a ação da associação da OT ao TF, em comparação às intervenções isoladas, no processo de remodelamento ósseo do colo do fêmur de ratas Wistar na periestropausa (18 a 21 meses). Quarenta ratas Wistar com ciclo estral irregular (18 meses) foram randomizadas nos grupos: 1- Veículo (Veh); 2-Ocitocina (Ot); 3-Treinamento de força (Tf); 4-Ot+Tf. Os animais do grupo 1 receberam salina (0,15 mol/L) e dos grupos 2 e 4 receberam OT (134 µg/kg), sendo duas injeções intraperitoneais com intervalo de 12 horas a cada 30 dias, totalizando 8 injeções ao final do período experimental. Os animais dos grupos 3 e 4 realizaram TF em escada 3 vezes por semana com realização mensal do teste de capacidade de carga máxima voluntária (CCMV). Após 120 dias, os animais foram eutanasiados, os fêmures foram coletados para análises de ensaio mecânico, densitometria, microtomografia óssea, espectroscopia de Raman e técnica de reação em cadeia da polimerase de transcrição reversa em tempo real (qRT-PCR), e o sangue para análises de marcadores bioquímicos do metabolismo ósseo, dano hepático e estresse oxidativo. A principal novidade deste estudo é a adição da OT ao TF, a qual apresentou, no ensaio de compressão, maior força máxima em relação ao Veh e menor elasticidade em relação ao Tf e, no ensaio de flexão de três pontos, maior rigidez em relação ao Veh e Ot, menor rigidez e menor elasticidade em relação ao Veh; maior espessura cortical (Ct.Th) em relação aos demais grupos, menor número de poros (Po.N) em relação ao Veh e Ot, e maior momento polar médio (J) em relação ao Tf. Houve também maior volume do osso trabecular (BV/TV) em relação ao Ot e maior espessura trabecular (Tb.Th) em relação aos demais grupos. A densidade mineral óssea areal (aDMO) do colo do fêmur foi maior que o Ot, e a DMO do fêmur total foi maior que os demais grupos. Quanto a expressão gênica, houve maior expressão do fator de transcrição relacionado ao Runt 2 (Runx2) em relação ao Veh, o fator de transcrição Osterix (Osx/Sp7) foi menor que o Ot e Tf. A proteína morfogenética óssea 2 (Bmp2) apresentou menor expressão em relação ao Veh, e a expressão da fosfatase alcalina óssea (Fal) foi maior que os demais grupos. A expressão do membro da família do fator de necrose tumoral 11b (Opg) e do ligante do fator de necrose tumoral (Rankl) foi maior que os outros grupos, a expressão do membro do fator de necrose tumoral 11a (Rank) e catepsina K (Ctsk) foi maior que Veh e Ot. Também foi observado menor atividade de fosfatase ácida resistente ao tartarato (TRAP) e capacidade antioxidante total (CAT) no ensaio bioquímico em relação aos demais grupos. Na intervenção com OT, houve maior elasticidade no ensaio de flexão de três pontos, e maior Ct.Th em relação ao Veh. A expressão gênica de Runx2, Osx/Sp7 foi maior e Bmp2 foi menor que o grupo Veh. No TF houve maior elasticidade que o Veh e Ot no ensaio de compressão, maior rigidez e elasticidade em relação ao Veh no ensaio de flexão de três pontos. Houve menor Ct.Th em relação ao Ot, maior DMO do fêmur total em relação ao Veh, e a taxa de mineralização foi maior que o Veh e Ot. Na expressão gênica, Runx2 e Osx/Sp7 foram maiores que o Veh. A Bmp2 e osteocalcina/proteína óssea gama-carboxiglutamato (Ocn) foram menores que o Veh, e a Fal foi menor que Ot. Em relação a Rank e Ctsk, estas foram maiores que Veh e Ot. Por fim, a atividade de aspartato aminotransferase (AST) foi menor que o Veh. Esses resultados mostraram que a associação de intervenções é estratégia anabólica promissora para a prevenção da osteoporose no período da periestropausa, destacando-se dos efeitos das intervenções isoladas, ao preservar aspectos mecânicos, estruturais e gênicos do osso, além de parecer controlar fatores relacionados ao cross-talk entre tecido ósseo e tecido adiposo a favor da homeostase oxidativa e de fatores relacionados a atividade de marcadores ósseos(AU)

The decrease in estrogen concentrations, such as that which occurs during perimenopause and menopause, contributes to an increase in bone turnover, with a rate of resorption higher than that of bone formation, which favors the installation of osteoporosis, a silent disease that determines bone fragility and greater probability of fractures. Among the interventions used to prevent osteoporosis, strength training (ST) and oxytocin (OT), a promising hormone with anabolic action on bone, stand out. The objective of this study was to verify the action of the association of OT and ST, compared to isolated interventions, in the process of bone remodeling of the femoral neck of Wistar rats in periestropause (18 to 21 months). Forty Wistar rats with irregular estrous cycle (18 months) were randomized into groups: 1-Vehicle (Veh); 2-Oxytocin (Ot); 3-Strength training (St); 4-Ot+St. The animals in group 1 received saline (0.15 mol/L) and in groups 2 and 4 received OT (134 µg/kg), with two intraperitoneal injections with an interval of 12 hours every 30 days, totaling 8 injections at the end of the period. trial period. The animals in groups 3 and 4 performed ST on a ladder 3 times a week with monthly performance of the maximum voluntary carrying capacity test (MVCC). After 120 days, the animals were euthanized, the femurs were collected for mechanical assay analysis, densitometry, bone microtomography, Raman spectroscopy and real-time reverse transcription polymerase chain reaction (qRT-PCR) technique, and blood for analysis of biochemical markers of bone metabolism, liver damage and oxidative stress. The main novelty of this study is the addition of OT to ST, which presented, in the compression test, greater maximum force in relation to Veh and less elasticity in relation to St and, in the three-point bending test, greater stiffness in relation to to Veh and Ot, less rigidity and less elasticity in relation to Veh; greater cortical thickness (Ct.Th) in relation to the other groups, smaller number of pores (Po.N) in relation to Veh and Ot, and greater mean polar moment (J) in relation to St. There was also greater trabecular bone volume (BV/TV) in relation to Ot and greater trabecular thickness (Tb.Th) in relation to the other groups. The areal bone mineral density (aBMD) of the femoral neck was higher than the Ot, and the BMD of the total femur was higher than the other groups. As for gene expression, there was greater expression of the transcription factor related to Runt 2 (Runx2) in relation to Veh, the transcription factor Osterix (Osx/Sp7) was lower than Ot and St. Bone morphogenetic protein 2 (Bmp2) showed lower expression compared to Veh, and boné alkaline phosphatase (Alp) expression was higher than the other groups. The expression of tumor necrosis factor 11b family member (Opg) and tumor necrosis factor ligand (Rankl) was higher than the other groups, tumor necrosis factor 11a member (Rank) and cathepsin K (Ctsk) was greater than Veh and Ot. It was also observed lower activity of tartrate resistant acid phosphatase (TRAP) and total antioxidant capacity (CAT) in the biochemical assay in relation to the other groups. In the intervention with OT, there was greater elasticity in the three-point bending test, and greater Ct.Th in relation to Veh. The gene expression of Runx2, Osx/Sp7 was higher and Bmp2 was lower than the Veh group. In ST intervention there was greater elasticity than Veh and Ot in the compression test, greater stiffness and elasticity in relation to Veh in the three-point bending test. There was lower Ct.Th in relation to Ot, higher BMD of the total femur in relation to Veh, and the mineralization rate was higher than Veh and Ot. In gene expression, Runx2 and Osx/Sp7 were higher than Veh. Bmp2 and osteocalcin/bone protein gammacarboxyglutamate (Ocn) were lower than Veh, and Fal was higher than Ot. In relation to Rank and Ctsk, these were higher than Veh and Ot. Finally, aspartate aminotransferase (AST) activity was lower than Veh. These results showed that the association of interventions is a promising anabolic strategy for the prevention of osteoporosis in the periestropause period, standing out from the effects of isolated interventions, by preserving mechanical, structural and genetic aspects of the bone, in addition to seeming to control factors related to the cross -talk between bone tissue and adipose tissue in favor of oxidative homeostasis and factors related to the activity of bone markers(AU)

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso)

ABSTRACT Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

Intercellular mediators in bone remodeling regulation in the experimental renal pathology / Mediadores intercelulares de la regulación de la remodelación ósea en un modelo experimental de patología renal

Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappa b receptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG). The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids. Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzymelinked immunoassay was used to measure intercellular mediator levels in the serum. The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals' blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group. In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future. (AU)

Las enfermedades metabólicas óseas se caracterizan por un desequilibrio en el proceso de remodelación ósea en los que participan mediadores tales como receptor del activador del factor nuclear- kappa- b (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, recuentemente empleados en el tratamiento de la enfermedad renal crónica, exacerban este desequilibrio. En la enfermedad esclerótica renal, las moléculas de adhesión celular P-selectina and galectina-3 tienen un rol fundamental. El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelación ósea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crónica con tratamiento glucocorticoideo. Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crónica con afección de la remodelación ósea (ERC); animales con afección de la remodelación ósea expuestos a glucocorticoides (GC); enfermedad renal crónica con afección de la remodelación ósea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioquímicamente, histológicamente y por medición de la densidad ósea. RANKL, OPG, Pselectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno análisis. En los 3 grupos experimentales la densidad ósea se evidenció reducida y los niveles séricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmática en GC y ERC+GC se encontró reducida y aumentada en los animales ERC, en comparación con los animales controles. La concentración sérica de P-selectina sérica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmáticos de los animales intactos. El avance del conocimiento sobre la regulación de la remodelación ósea a través de la interacción de mediadores sistémicos, en un futuro, puede conducir al desarrollo de nuevas estrategias terapéuticas para la prevención de la osteoporosis en pacientes con enfermedad renal crónica. (AU)

Fatores de risco que levam o adolescente a desenvolver osteoporose: revisão integrativa / Risk factors that take adolescent to develop osteoporosis: integration review / Factores de riesgo que levan el adolescente a desarrollar os-teoporosis: revisión integrativa

Avaliar os fatores de risco desde a adolescência, para o desenvolvimento da osteoporose. Trata-se de um estudo de revisão integrativa da literatura, onde foram utilizadas 4 etapas para analisar os artigos: 1ª etapa - linha norteadora. 2ª etapa - pesquisa bibliográfica na eletrônica de acesso aberto SciELO. 3ª etapa - leitura do título seguido do resumo do artigo desta pesquisa. 4ª etapa - interpretação/avaliação dos resultados foi baseada nas características. Foram localizados nas bases de dados da SciELO como: Coleção Brasil, Periódico Todos, Idioma Português, Ano de Publicação 2012 a 2018, SciELO Área Temática Ciências da Saúde. Foram localizados 187 artigos. A osteoporose pode ser prevenida na sua na forma secundária, a melhor estratégia para prevenção deve ser instituída a partir da infância.(AU)

To evaluate risk factors from adolescence to the development of osteoporosis. It is an integrative review of the literature, where 4 steps were used to analyze the articles: 1st stage - guiding line. 2nd stage - bibliographic research in the open access electronics SciELO. Step 3 - reading the title followed by the summary of the article of this research. Stage 4 - interpretation / evaluation of results was based on characteristics. It was located in the databases of SciELO as: Collection Brazil, Periodical All, Portuguese Language, Year of Publication 2012 to 2018, SciELO Subject Area Health Sciences. 187 articles were found. Osteoporosis can be prevented in its in the secondary form, the best strategy for prevention should be instituted from childhood. Keywords: adolescent; osteoporosis; health promotion.(AU)

Evaluar los factores de riesgo desde la adolescencia, para el desarrollo de la osteoporosis. Se trata de un estudio de revisión integrativa de la literatura, donde se utilizaron 4 etapas para analizar los artículos: 1ª etapa - línea orientadora. 2ª etapa - investigación bibliográfica en la electrónica de acceso abierto SciELO. 3ª etapa - lectura del título seguido del resumen del artículo de esta investigación. 4ª etapa - interpretación / evaluación de los resultados se basó en las características. Se encuentra en las bases de datos SciELO como: Colección Brasil, regular todo, el lenguaje portugués, Año de publicación 2012 y 2018, SciELO Área temática Ciencias de la Salud se localizaron 187 artículos. La osteoporosis puede prevenirse en su forma secundaria, la mejor estrategia para la prevención debe ser instituida a partir de la infancia.(AU)

Significado e considerações sobre a osteoporose por mulheres com e sem diagnóstico da doença / Meaning and considerations about osteoporosis by women with and without diagnosis of the disease

INTRODUÇÃO: Entre pacientes diagnosticados e em tratamento para osteoporose, acredita-se que há desconhecimento geral sobre a doença. Entre os pacientes em faixa etária de risco, não diagnosticados, crê-se que o desconhecimento é maior. OBJETIVO: Avaliar as considerações de mulheres sobre o conceito da osteoporose e sua prevenção. MÉTODOS: Estudo qualitativo, descritivo, realizado no Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, com 10 pacientes portadores de osteoporose, e 10 pacientes sem. A tabulação dos dados ocorreu por meio da utilização de três figuras metodológicas: ideia central, expressões chave e o discurso sujeito coletivo. O estudo foi aprovado pelo Comitê de Ética e Pesquisa com Seres Humanos. RESULTADOS: Dentre as pacientes com diagnóstico, destacou-se como ideias centrais a vulnerabilidade às fraturas e os conceitos de apresentação da doença como osteopenia e osteoporose. No grupo sem diagnóstico, 40% desconhecia a doença. Na prevenção, observou-se maior conhecimento no grupo portador da doença, sendo as ideias centrais destacadas: os exercícios físicos, alimentação rica em cálcio e vitamina D, além da exposição solar. CONCLUSÃO: Evidenciou-se um conhecimento limitado sobre a osteoporose e suas formas de prevenção, sobretudo no grupo sem diagnóstico, porém em faixa etária de risco. Assim, conclui-se que, tratando-se de uma doença de elevada prevalência, de altos custos orçamentários para a saúde pública, e com riscos significativos uma vez não diagnosticados e não tratada, medidas resolutivas de maior esclarecimento sobre a doença devem ser praticadas em todas as esferas da saúde pública.

INTRODUCTION: Among patients diagnosed and under treatment for osteoporosis, it is believed that there is general ignorance about the disease. Among undiagnosed patients at risk, it is believed that the lack of knowledge is larger. OBJECTIVE: To evaluate the considerations of women about the concept of osteoporosis and its prevention. METHODS: A qualitative, descriptive study was carried out at Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, with 10 patients with osteoporosis and 10 patients without the disease. Data tabulation occurred using three methodological figures: central idea, key expressions and collective subject discourse. The study was approved by the Committee of Ethics and Research with Human Beings. RESULTS: Among the diagnosed patients, the central ideas were vulnerability to fractures and the concepts of disease presentation like osteopenia and osteoporosis. In the undiagnosed group, 40% were unaware of the disease. About prevention, greater knowledge was observed in the group with the disease, with the main ideas being highlighted: physical exercises, calcium and vitamin D rich food, as well as sun exposure. CONCLUSION: There was limited knowledge about osteoporosis and its prevention, especially in the group without diagnosis, but in the age group at risk. Thus, it is concluded that, in the case of a disease of high prevalence, of high budgetary costs for public health, and with significant risks once it is undiagnosed and untreated, resolute measures of greater clarity about the disease should be practiced in all spheres of public health.

Beneficial effects of Cuscuta chinensis extract on glucocorticoid-induced osteoporosis through modulation of RANKL/OPG signals

Cuscuta chinensis Lam. (Convolvulaceae) is an important herbal medicine widely used to improve sexual function, treat osteoporosis, and prevent aging, and has been reported to exhibit anti-osteoporotic effects in vitro. However, the activity of Cuscuta chinensis Lam. on glucocorticoid-induced osteoporosis still remains unclear. The present study aimed to assess the protective effect and the underlying mechanism of action of Cuscuta chinensis extract (CCE) against glucocorticoid-induced osteoporosis in vivo. Sprague-Dawley rats were randomly divided into four groups as follows: control group, osteoporosis group, and 2 CCE-treated osteoporosis groups (100 mg·kg-1·day-1). Blood samples and femur bones were collected for immunohistochemistry, biochemical, mRNA expression, and western blot analysis. HPLC analysis revealed that chlorogenic acid, quercetin, and hyperin were the major constituents of CCE. The results indicated that CCE increased bone length, bone weight, and bone mineral density and suppressed dexamethasone (DEX)-induced reduction in body weight. In addition, TRAP staining indicated that CCE reduced osteoclasts in DEX-induced osteoporosis rats. Mechanistically, CCE treatment alleviated the increase of bone resorption markers and the decline of osteogenic markers, which might be partially mediated by regulation of RANKL/OPG and RunX2 pathways. These results suggest that CCE showed promising effects in the protection against glucocorticoid-induced osteoporosis through protecting osteoblasts and suppressing osteoclastogenesis.

Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture

Abstract Purpose: To evaluate the effects of food restriction on fracture healing in growing rats. Methods: Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. Results: Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. Conclusion: Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.

La terapia hormonal de la menopausia ¿disminuye el riesgo de enfermedades crónicas? / Does menopause hormone therapy reduce the risk of chronic diseases?

The hormonal deficit of post menopause is not only linked to the classic hot flashes, but also to a higher risk of chronic diseases. Menopausal hormone therapy (MHT) adequately treats climacteric symptoms and can prevent some chronic diseases such as osteoporosis. The Women's Health Initiative (WHI) study, which indicated risks of MHT in elderly postmenopausal women, caused a massive withdrawal of this therapy. But, in recent years the results of the WHI have been challenged by methodological problems and by several studies indicating that, if MHT is initiated early and the non-oral route is preferred, the risks could be minimized and it could improve not only the quality of life but also reduce the risk of chronic diseases. However, the US Preventive Services Task Force (USPSTF) recommends against the use of MHT for the prevention of chronic diseases, a position that has been challenged by publications of the North American Menopause Society and the International Menopause Society. This controversy persists so far. We report data that suggest a preventive role of MHT in perimenopausal women.

Analysis of lifestyle and bone mineralization in a population of Spanish young adults / Análisis de los estilos de vida y la mineralización ósea en una población de adultos jóvenes españoles

Abstract Objective: To analyze the environmental factors (nutritional status, levels of physical activity and nutritional habits) and their possible association with bone mass in a population of young adults. Methods: The study population consisted of 200 subjects (117 women and 83 men) aged between 18 and 25 years (mean age 20.4 years ±2.2 years). Body composition parameters were measured by an electronic balance (TANITA BC-418MA), nutritional habits were estimated by 72-h dietary recall, level of physical activity was assessed by the International Physical Activity Questionnaire (IPAQ) and bone mass was measured by ultrasonography at the calcaneus. Results: There were significant differences in bone mass values ​​according to gender (p= 0.013). Despite the fact that 70% of the subjects had a body mass index (BMI) within the normal range, 20% had overweight or obesity. 49% of the individuals had a moderate level of physical activity, although women had lower levels of physical activity than men (17.9% vs 8.4%). Most diets among young adults were hyperprotic, hyperlipidic and low-carbohydrates, with low-calcium and fiber intakes and high-phosphorus. Analysis of bone mass according to BMI showed higher values ​​as the weight category rises, with significant differences in women. Higher values ​​of bone mass were shown as the level of physical activity was higher, showing significant differences in males. Conclusion: Our results show that BMI and level of physical activity are significantly associated with bone health in a population of young adults, suggesting the relevance of promoting healthy lifestyles as a strategy for the early prevention of osteoporosis.

Resumen Objetivo: Analizar los factores ambientales (estado nutricional, nivel de actividad física y hábitos nutricionales) y su posible relación con los niveles de masa ósea en una población de adultos jóvenes. Métodos: La población de estudio estuvo constituida por 200 sujetos (117 mujeres y 83 hombres) de edades comprendidas entre 18 y 25 años (edad media 20.4 años ± 2.2 años). La composición corporal se evaluó con balanza electrónica (TANITA BC-418MA), la valoración de los hábitos nutricionales mediante Recordatorio de 72 h, el nivel de actividad física a través del Cuestionario Internacional de Actividad Física (IPAQ) y la masa ósea mediante ultrasonografía en el calcáneo. Resultados: Existen diferencias estadísticamente significativas en los valores de masa ósea en función del sexo (p= 0.013). A pesar de que el 70% de los sujetos presentaron un índice de masa corporal (IMC) dentro de los límites de la normalidad, un 20% padece sobrepeso y obesidad. El 49% de los individuos tenian un nivel moderado de actividad física, aunque las mujeres presentaron niveles más bajos de actividad física que lo varones (17.9% vs 8.4%). Las dietas mayoritarias entre los adultos jóvenes son hiperprotéicas, hiperlipídicas y bajas en hidratos de carbono, observándose una ingesta baja de calcio y fibra y alta en fósforo. El análisis de la masa ósea en función de IMC mostró valores mayores conforme asciende la categoría ponderal, existiendo diferencias significativas en mujeres. Igualmente, se muestran valores más altos de masa ósea conforme mayor es el nivel de actividad física, evidenciando diferencias significativas en los varones. Conclusión: Nuestros resultados muestran que el índice de masa corporal y el nivel de actividad física se asocian significativamente con la salud ósea en una población de adultos jóvenes, evidenciando la importancia del fomento de estilos de vida saludables como estrategia para la prevención temprana de la osteoporosis.