Effect of walking with blood flow restriction in elderly women with osteoporosis/osteopenia / Efeito da caminhada com restrição do fluxo sanguíneo em idosas com osteoporose/osteopenia

Abstract Introduction The preservation of bone mass in elderly women is associated with better levels of practice of systematic physical exercises. Aerobic training combined with blood flow restriction seems to be a new alternative that determines this process, but knowledge gaps are still observed when referring to exercise associated with blood flow restriction (BFR) and adaptations on bone variables. Objective To analyze the chronic effects of aerobic training with and without BFR on bone mineral density and bone biomarker osteocalcin concentrations in older women. Methods Thirty women were randomized into the following groups: walking on a treadmill at low intensity with BFR; moderate treadmill walking with no BFR; only BFR (no exercise) for 20 minutes, twice a week, for 24 weeks. Bone mineral density was measured before and 24 weeks after intervention. Blood serum osteocalcin concentrations were measured before, 12 and 24 weeks after intervention. Results There were no differences between groups in bone mineral density (femoral neck, p = 0.31; total femur, p = 0.17; lumbar spin, p = 0.06) and osteocalcine (W(2) = 0.27; p = 0.87) ouctomes after 24 weeks of intervention. Conclusion There was no difference between walking training, blood flow restriction only, or walking+blood flow restriction on bone mineral density and osteocalcin concentrations after 24-weeks of intervention in older women with osteopenia/osteoporosis.

Resumo Introdução A preservação da massa óssea em mulheres idosas está associada a melhores níveis de prática de exercícios físicos sistemáticos. O treinamento aeróbico combinado com restrição de fluxo sanguíneo (RFS) parece ser uma nova alternativa que determina esse processo, mas ainda são observadas lacunas de conhecimento quando se refere ao exercício associado à RFS e adaptações nas variáveis ósseas. Objetivo Analisar os efeitos crônicos do treinamento aeróbico com e sem RFS na densidade mineral óssea e nas concentrações do biomarcador ósseo osteocalcina em mulheres idosas. Métodos Trinta mulheres foram randomizadas nos seguintes grupos: caminhada em esteira de baixa intensidade com RFS; caminhada moderada em esteira sem RFS; apenas RFS (sem exercícios) por 20 minutos, duas vezes por semana, durante 24 semanas. A densidade mineral óssea foi medida antes e 24 semanas após a intervenção. As concentrações séricas de osteocalcina no sangue foram medidas antes, 12 e 24 semanas após a intervenção. Resultados Não houve diferenças entre os grupos na densidade mineral óssea (colo do fêmur, p = 0,31; fêmur total, p = 0,17; giro lombar, p = 0,06) e osteocalcina (W(2) = 0,27; p = 0,87) após 24 semanas de intervenção. Conclusão Não houve diferença entre treinamento de caminhada, apenas restrição de fluxo sanguíneo ou caminhada + restrição de fluxo sanguíneo na densidade mineral óssea e nas concentrações de osteocalcina após 24 semanas de intervenção em mulheres idosas com osteopenia/osteoporose.

Análise da influência de solução de biovidro no procedimento endodôntico regenerativo / Analysis of the influence of bioglass solution on the regenerative endodontic procedure

Este estudo avaliou os efeitos de uma solução experimental de vidro bioativo F18 dopado com cobalto (F18Co) no reparo tecidual após procedimento endodôntico regenerativo (REP, do inglês regenerative endodontic procedure) em molares de ratos. A solução de F18Co foi preparada misturando o pó de F18Co com água destilada na proporção de 1:5. Os primeiros molares superiores direito ou esquerdo de 12 ratos Wistar foram utilizados, nos quais as polpas foram expostas, removidas e os canais irrigados com hipoclorito de sódio (NaOCl) 2,5%, seguido de ácido etilenodiaminotetraacético (EDTA) 17% (5 min cada). Em seguida, os molares foram divididos em dois grupos (n = 6): REP-SS e REP-F18Co, nos quais receberam irrigação final (5 min) com solução salina (SS) ou solução de F18Co, respectivamente. Em seguida, foi induzido sangramento intracanal e o dente foi selado. Molares não tratados foram usados como controles (n = 3). Após 21 dias, os ratos foram eutanasiados e as peças processadas para análise da formação de tecido mineralizado e tecido mole dentro do canal radicular, pela técnica de hematoxilinaeosina. A presença e maturação do colágeno foram avaliadas por coloração de tricrômio de Masson e picrosírius red. Análises da imunomarcação do antígeno nuclear de proliferação celular (PCNA) e osteocalcina (OCN) foram realizadas. Os dados foram submetidos ao teste de Mann-Whitney U (p < 0,05). Houve formação semelhante de tecido mineralizado em espessura e comprimento nos grupos REP-SS e REP-F18Co (p > 0,05). Em relação à presença de tecido neoformado no interior dos canais radiculares, a maioria dos espécimes de REP-F18Co apresentou formação de tecido até o terço cervical do canal radicular, enquanto do grupo REP-SS, até o terço médio (p < 0,05), e houve maior maturação colágena em REP-F18Co (p < 0,05). O número de células positivas para PCNA encontradas no terço apical do canal radicular foi significativamente maior em REP-F18Co, assim como a imunomarcação de OCN, que foi severa na maior parte dos espécimes do grupo REP-F18Co, e leve em REPSS. Conclui-se que a irrigação final com solução de biovidro F18Co em REP não influenciou a formação de tecido mineralizado, mas induziu a formação de tecido conjuntivo no interior dos canais radiculares, com maior maturação colágena, aumento no número de células positivas para PCNA e na imunomarcação de OCN.

This study evaluated the influence of an experimental solution of cobalt-doped F18 bioactive glass (F18Co) on tissue repair following regenerative endodontic procedure (REP) in rat molars. The F18Co solution was prepared at a ratio of 1:5 F18Co powder to distilled water. The right or left upper first molars of 12 Wistar rats were used, where the pulps were exposed, removed, and irrigated with 2.5% sodium hypochlorite (NaOCl), followed by 17% ethylenediaminetetraacetic acid (EDTA) (5 min each). Subsequently, the molars were divided into two groups (n = 6): REP-SS and REP F18Co, where they received a final irrigation (5 min) with saline solution (SS) or F18Co solution, respectively. Then, intracanal bleeding was induced, and the tooth was sealed. Untreated molars were used as controls (n = 3). At 21 days, the rats were euthanized, and the specimens were processed for analysis of mineralized tissue and soft tissue formation inside the root canal using haematoxylin-eosin. The presence and maturation of collagen was evaluated by Masson's trichrome and picrosirius red staining. Immunolabeling analyses of proliferating cell nuclear antigen (PCNA) and osteocalcin (OCN) were performed. The data were submitted to the Mann-Whitney U test (P < 0.05). There was similar formation of mineralized tissue in thickness and length in REP-SS and REP-F18Co groups (P > 0.05). Regarding the presence of newly formed soft tissue, most specimens of the REP-F18Co had tissue formation up to the cervical third of the canal, while the REP-SS specimens showed formation up to the middle third (P < 0.05), and there was higher maturation collagen in REP-F18Co (P < 0.05). The number of PCNA-positive cells found in the apical third of the root canal was significantly higher in the F18Co group, as well as the OCN immunolabeling, which was severe in most specimens of REP-F18Co, and low in most specimens of REP SS. In conclusion, the final irrigation with F18Co bioactive glass solution in REP did not influence mineralized tissue formation but induced soft tissue formation inside the root canals, with higher collagen maturation, and an increase in PCNA-positive cells and OCN immunolabeling

Effects of teriparatide on bone formation in rats with experimentally induced premaxillary expansion

ABSTRACT Objective: This study aimed to evaluate the effects of systemic teriparatide on sutural bone formation after premaxillary suture expansion in rats. Material and Methods: Twenty Wistar male rats (8-10 weeks old) were randomly divided into two groups, namely, control (C, n=10) and teriparatide (T, n=10). An expansion force was applied to the maxillary incisors using helical spring for a seven-day expansion period, for both groups. On the eighth day, the rats were kept for a seven-day consolidation period, and then 60 µg/kg teriparatide (once a day) was administered to group T subcutaneously for seven days. Then, all the rats were sacrificed, and histological sections were stained with hemotoxylin-eosin for examination. Anti-osteonectin, anti-osteocalcin, anti-Vascular endothelial growth factor (VEGF) and anti-transforming growth factor beta (TGF-β) were evaluated by immunohistochemical analysis in the midpalatal suture area. Results: Histologically, the newly formed bone tissue was observed to be larger in group T than in group C. The number of immunoreactive osteoblasts for osteonectin, osteocalcin and VEGF antibodies was significantly higher in group T than in group C (p = 0.0001). The TGF-β antibody showed a mild reaction in group T, but did not reach significance in comparison with group C (p ˃ 0.05). Conclusion: Systemic teriparatide application following the premaxillary expansion of the suture area may stimulate bone formation and add to the consolidation of the expansion in rats by regulating osteonectin, osteocalcin and VEGF.

RESUMO Objetivo: O presente estudo teve como objetivo avaliar os efeitos do uso sistêmico da teriparatida na formação óssea sutural após a expansão da pré-maxila em ratos. Material e Métodos: Vinte ratos machos da raça Wistar (com oito a dez semanas de vida) foram divididos aleatoriamente em dois grupos: controle (C, n=10) e teriparatida (T, n=10). Uma força de expansão foi aplicada aos incisivos superiores, usando uma mola helicoidal, por um período de expansão de sete dias em ambos os grupos. No oitavo dia, os ratos iniciaram um período de sete dias de consolidação, nos quais 60 µg/kg de teriparatida foram administrados (uma vez ao dia), por via subcutânea, para o grupo T. Posteriormente, todos os ratos foram sacrificados e cortes histológicos corados com hemotolixina-eosina foram examinados. Por meio de análise imuno-histoquímica da região da sutura palatina mediana, avaliou-se a presença de anti-ostenectina, anti-osteocalcina, anti-fator de crescimento endotelial vascular (VEGF) e anti- fator transformador de crescimento (TGF-β). Resultados: Histologicamente, observou-se que o tecido ósseo recém-formado foi maior no grupo T do que no grupo C. O número de osteoblastos imunorreativos para anticorpos de osteonectina, osteocalcina e VEGF foi significativamente maior no grupo T do que no grupo C (p = 0,0001). O anticorpo TGF-β mostrou uma pequena reação no grupo T; porém, sem diferença significativa para o grupo C (p ˃ 0,05). Conclusão: O uso sistêmico de teriparatida após a expansão da sutura na região da pré-maxila pode estimular a formação óssea e melhorar a consolidação da expansão em ratos, por meio da regulação de osteonectina, osteocalcina e VEGF.

Asociación de parámetros bioquímicos del metabolismo óseo con progresión y/o desarrollo de nuevas calcificaciones aórticas / Association of biochemical parameters of bone metabolism with progression and/or development of new aortic calcifications

Objetivo: Los parámetros bioquímicos siguen siendo la opción más utilizada para el seguimiento de pacientes con alteraciones metabólicas óseas. El objetivo del estudio fue valorar la asociación de algunos marcadores bioquímicos del metabolismo óseo con aparición y progresión de calcificaciones aórticas. Material y métodos: Se seleccionaron aleatoriamente 624 hombres y mujeres mayores de 50 años que cumplimentaron un cuestionario y a los que se realizaron dos radiografías laterales dorso?lumbares y densitometría ósea. Cuatro años más tarde, en 402 sujetos se repitieron los mismos estudios junto con un estudio bioquímico. Resultados: La edad y la proporción hombres fue superior en los que tuvieron “progresión global” de calcificación aórtica (progresión de las ya existentes más las nuevas). Los niveles séricos de calcio y calcitriol fueron significativamente superiores y los de osteocalcina significativamente inferiores en los que se observó “progresión global” de calcificación aórtica. El análisis multivariante mostró que únicamente la osteocalcina se asoció de forma independiente con “progresión global” de calcificación aórtica, con una disminución del 18% por cada incremento de 1 ng/mL en los niveles de osteocalcina (odds ratio (OR)=0,82; intervalo de confianza del 95% (IC 95%): 0,71-0,92). La categorización de la osteocalcina en terciles mostró que los sujetos del primer tercil (<4,84 ng/mL) se asociaron con mayor proporción de nuevas calcificaciones aórticas: (OR=2,45; IC 95%: 1,03-3,56) respecto al tercer tercil (>6,40 ng/mL). Conclusión: Los niveles séricos de osteocalcina podrían ser un marcador bioquímico para evaluar la aparición y/o a evolución de la calcificación aórtica. No obstante, se necesita determinar con mayor precisión como podría ejercer este efecto protector en el proceso de calcificación vascular (AU)

Objetive: Biochemical parameters continue to be the most widely used option for the follow-up of patients with bone metabolic disorders. The objective of our study was to assess the association of some biochemical markers of bone metabolism with the appearance and progression of aortic calcifications. Material and methods: In this study, 624 men and women older than 50 years were selected at random. The participants completed a questionnaire and underwent two lateral dorsal-lumbar x-rays and bone densitometry. Four years later, the same studies were repeated in 402 subjects along with a biochemical study. Results: Age and the proportion of men were higher in those who had “global progression” of aortic calcification (progression of the existing ones plus new ones). The serum levels of calcium and calcitriol were significantly higher and those of osteocalcin significantly lower in which “global progression” of aortic calcification was observed. Multivariate analysis showed that only osteocalcin was independently associated with “global progression” of aortic calcification, with an 18% decrease for each 1 ng/mL increase in osteocalcin levels (odds ratio (OR)=0, 82; 95% confidence interval (95% CI): 0.71-0.92). The categorization of osteocalcin into tertiles showed that the subjects of the first tertile (<4.84 ng/mL) were associated with a higher proportion of new aortic calcifications: (OR=2.45; 95% CI: 1.03-3, 56) with respect to the third tertile (>6.40 ng/mL). Conclusion: Serum levels of osteocalcin could be a biochemical marker to evaluate the appearance and/or evolution of aortic calcification. However, it is necessary to determine with greater precision how it could exert this protective effect in the process of vascular calcification. (AU)

Influência do LED Violeta associado ou não ao gel clareador na inflamação, mineralização e maturação colágena do tecido dentinário e pulpar / Influence of violet LED associated or not with peroxide gel on inflammation, mineralization, and collagen fiber maturation in dentin and pulp tissue

Objetivo: Avaliar a influência do LED Violeta, associado ou não ao gel clareador a base de peróxido de hidrogênio (PH) a 17,5% no complexo dentino-pulpar de ratos. Materiais e métodos: Molares superiores de 80 ratos foram distribuídos nos grupos (n = 10): CONT ­ sem tratamento, PH ­ 1 aplicação de 30 minutos de PH a 17,5%, LED ­ 1 aplicação de 20 minutos do LED Violeta, e PH+LED - aplicação do PH e LED Violeta. Imediatamente (T0), e aos 7 (T1), 15 (T2) e 30 dias (T3) após o tratamento, os ratos foram eutanasiados e as maxilas processadas para avaliação histológica, imunoistoquímica (IL-17, IL-23 e osteocalcina), e de picrosírius red, sendo realizados os testes de Wilcoxon e Mann-Whitney e Teste-T pareado e Teste-T, respectivamente. (α = 0,05). Resultados: Necrose e infiltrado inflamatório severo foram observados nos grupos PH e PH+LED. Apenas o grupo PH+LED manteve a imunomarcação severa para IL-17 e IL-23, diferindo do grupo LED e PH que apresentaram moderada imunomarcação em T0. Os grupos PH e PH+LED apresentaram severa imunomarcação de OCN em T2 e moderada imunomarcação em T3. O grupo LED apresentou menor quantidade de fibras imaturas em T2 e T3 que o grupo CONT. Conclusão: A terapia com LED violeta não induziu inflamação e fibrose no tecido pulpar, apesar de acelerar a maturação das fibras de colágeno da dentina e, quando associada ao peróxido de hidrogênio, pode tornar os dentes mais sensíveis(AU)

Objective: Was to evaluated the influence of the Violet LED, associated or not with a 17.5% hydrogen peroxide (HP) bleaching gel in the dentin-pulp complex of rats. Materials and methods: Upper molars of eighty Wistar rats were distributed in the groups (n = 10): CONT - without treatment, HP - 1 application of 30 minutes of 17.5% HP, LED - 1 application of 20 minutes of the Violet LED, and HP+LED - application of HP and LED Violet. Immediately (T0), and at 7 (T1), 15 (T2) and 30 days (T3) after treatment, the rats were euthanized and the jaws were processed for histological, immunohistochemical evaluation (IL-17, IL-23 and osteocalcin), and picrosirius red, with Wilcoxon and Mann-Whitney tests and paired T-test and T-test, respectively (α = 0.05). Results: Necrosis and severe inflammatory infiltrate were observed in the PH and PH+LED groups. Only the PH+LED group maintained severe immunostaining for IL-17 and IL-23, differing from the LED and PH group which presented moderate T0 immunostaining. The PH and PH+LED groups presented severe immunostaining of OCN in T2 and moderate immunostaining in T3. The LED group had a lower amount of immature fibers in T2 and T3 than the CONT group. Conclusion: Violet LED therapy induced no inflammation and fibrosis in the pulp tissue, however accelerating the maturation of dentin collagen fibers and, when associated with hydrogen peroxide, can make the teeth more sensitive(AU)

La osteocalcina: de marcador de formación ósea a hormona; y el hueso, un órgano endocrino / Osteocalcin: from marker of bone formation to hormone; and bone, an endocrine organ

La osteocalcina es una proteína sintetizada por el osteoblasto. Antes de ser liberada a la matriz extracelular, la osteocalcina humana sufre una gamma-carboxilación, al unirse en las posiciones 17, 21 y 24 el ácido gamma-carboxi-glutámico. A la circulación pasa parte de osteocalcina carboxilada y descarboxilada. Desde su descubrimiento a finales de los años 70, se ha utilizado como marcador de formación ósea al ser un producto osteoblástico, y desconociéndose su papel en el organismo. En estos últimos años se ha descubierto que la osteocalcina es, en realidad, una hormona, y el hueso un órgano endocrino. La osteocalcina que actúa como hormona es la forma descarboxilada. La osteocalcina interviene en la homeostasis de la glucosa, en el funcionamiento del músculo esquelético, en el desarrollo cerebral, la fertilidad masculina, la esteatosis hepática y la calcificación arterial. En realidad todos estos hechos se han probado en ratones, pero existen indicios importantes de que esto podría ocurrir en humanos. Nos encontramos ante hechos que, de probarse, tendrían una enorme trascendencia clínica. (AU)

Osteocalcin is a protein synthesized by the osteoblast. Before being released into the extracellular matrix, human osteocalcin undergoes gamma-carboxylation, as gamma-carboxy-glutamic acid binds at positions 17, 21 and 24. Part of the carboxylated and decarboxylated osteocalcin passes into the circulation. Since its discovery in the late 70s, it has been used as a marker of bone formation as it is an osteoblastic product and its role in the body is unknown. In recent years, osteocalcin has been identified as a hormone. Bone is considered an endocrine organ. Osteocalcin acting as a hormone is the decarboxylated form. Osteocalcin is involved in glucose homeostasis, skeletal muscle function, brain development, male fertility, hepatic steatosis, and arterial calcification. All of these facts have actually been tested in mice, but there is strong evidence that this could occur in humans. We are faced with facts that, if proven, would have enormous clinical significance. (AU)

Predictive value of the bone markers osteocalcin and C-terminal telopeptide for jaw osteonecrosis in high-risk prostate cancer patients on bisphosphonate therapy: A prospective study. / Valor predictivo de los marcadores oseos osteocalcina y telopéptido C terminal para la osteonecrosis mandibular en pacientes con cáncer de próstata (CaP) de alto riesgo bajo tratamiento con bifosfonatos: estudio prospectivo.

OBJECTIVE: To examine the predictive value of osteocalcin (OC) and C-terminal telopeptide (CTX) levels for jaw osteonecrosis in high-risk prostate cancer (PCa) patients taking bisphosphonates (BPs). METHODS: Twenty-four patients were prospectively recruited in this study and followed from 2011 to 2015. All patients were diagnosed with metastatic PCa with secondary bone deposits and were on androgen deprivation therapy (ADT). All participants were started on 4mg of zoledronic acid intravenously every 4 weeks for two years. The patients were reviewed every three months with full blood count, blood biochemistry, PSA and measurement of OC and CTX. Patients also underwent dental/oral examination. OC and CTX levels in serum were calculated using the ELISA method. RESULTS: A significant decrease in PSA levels was found (ß=-0.06, SE=0.02, p=0.006). The levels of OC (ß=-0.46, SE=0.14, p=0.001) and CTX (ß=-0.01, SE=0.004, p=0.007) also decreased significantly during the two years of follow up. Osteonecrosis of the jaw was identified in three patients at two years. Patients with osteonecrosis also showed a decrease in OC and CTX levels. The mean OC reduction was 77.3% for patients with osteonecrosis and 12.6% for patients without osteonecrosis. The mean CTX reduction was 44.1% for patients with osteonecrosis and 9.62% for patients without osteonecrosis. CONCLUSION: Our study demonstrated no clear association between the levels of serum OC and CTX and bisphosphonate-related osteonecrosis of the jaw (BRONJ). To date, there is no clinically useful biomarker for the prediction of jaw osteonecrosis. More studies are needed using different bone turnover markers in order to identify patients at risk for BRONJ.

OBJETIVO: Examinar el valor predictivo de los niveles de osteocalcina (OC) y telopéptido C terminal (TCT) para la osteonecrosis mandibular en pacientes con cáncer de próstata de alto riesgo en tratamiento con bifosfonatos.MÉTODOS: Veintidós pacientes fueron reclutados prospectivamente en este estudio y seguidos desde 2011 a 2015. Todos los pacientes tenían el diagnóstico de CaP de próstata de alto riesgo con depósitos óseos secundarios y seguían tratamiento de deprivación androgénica (TDA). Todos los pacientes comenzaron con 4 mg de ácido zolendrónico IV cada 4 semanas durante 2 años. Los pacientes siguieron revisiones cada tres meses con hemograma, bioquímica sanguínea, PSA y mediciones de OC y TCT. Los pacientes fueron sometidos a evaluación dental/oral. Los niveles de OC y TCT en suero fueron medidos utilizando un método de ELISA. RESULTADOS: Se encontró un descenso significativo de los niveles de PSA (ß=-0,06, SE=0,02, p=0,006). Los niveles de OC (ß=-0,46, SE=0,14, p=0,001) y TCT ß=-0,01, SE=0,004, p=0,007) también disminuyeron significativamente durante los dos años de seguimiento. Se identificó osteonecrosis en tres pacientes en dos años. Los pacientes con osteonecrosis de mandíbula en tres pacientes a los dos años. Los pacientes con osteonecrosis también mostraron un descenso de los niveles de OC y TCT. La reducción media de OC fue del 77,3% en los pacientes con osteonecrosis y 12,6% en los pacientes sin osteonecrosis. La reducción media de TCT fue del 44,1% en los pacientes con osteonecrosis y 9,62% en los pacientes sin osteonecrosis. CONCLUSIONES: Nuestro estudio no demuestra una clara asociación entre los niveles séricos de OC y TCT y la osteonecrosis mandibular relacionada con bifosfonatos. Hasta la fecha, no hay un marcador clínico útil para la predicción de la osteonecrosis mandibular. Son necesarios más estudios utilizando diferentes marcadores de renovación ósea para identificar los pacientes en riesgo de osteonecrosis mandibular relacionada con bifosfonatos.

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives / Alterações na densidade mineral óssea e nos marcadores de formação óssea em adolescentes usuárias ou não de contraceptivos hormonais orais combinados por período de um ano

Abstract Objective: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. Methods: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n = 42) (20 µg EE/150 µg desogestrel), oral contraceptives 2 (n = 66) (30 µg EE/3 mg drospirenone), and a control group (n = 70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. Results: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. Conclusion: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Resumo: Objetivo: O objetivo deste estudo foi avaliar os efeitos de dois contraceptivos orais combinados de baixa dosagem por um ano sobre o metabolismo ósseo em adolescentes. Métodos: Este foi um estudo quase experimental. As adolescentes foram divididas em três grupos: contraceptivos orais 1 (n = 42) (20 µg de EE/150 µg de desogestrel), contraceptivos orais 2 (n = 66) (30 µg EE/3 mg de drospirenona) e grupo controle (n = 70). As adolescentes foram submetidas à avaliação antropométrica e densitometria (raio-X de dupla energia). Foram avaliados a idade óssea e os marcadores de formação óssea (osteocalcina e fosfatase alcalina óssea). As usuárias de contraceptivos orais foram novamente avaliadas após 12 meses. A análise de regressão linear foi utilizada para estudar, indiretamente, o efeito de cada ano adicional da idade cronológica sobre as variáveis antropométricas e densitométricas e sobre os marcadores ósseos no grupo de controle. Resultados: No início do estudo, não foram observadas diferenças significativas nas variáveis analisadas entre as usuárias de contraceptivos orais 1, contraceptivos orais 2 e o grupo controle. A análise de regressão linear mostrou um aumento na densidade mineral óssea e no conteúdo mineral ósseo para cada ano adicional. Houve uma redução significativa nos níveis de fosfatase alcalina óssea e não foi observada diferença significativa para osteocalcina nos indivíduos controles. A comparação das variáveis do raio-X de dupla energia no início e após um ano não mostrou diferença significativa no grupo de contraceptivos orais 1 ou contraceptivos orais 2. Foi observada uma redução significativa nos níveis de fosfatase alcalina óssea e osteocalcina nos dois grupos contraceptivos orais 1 e contraceptivos orais 2. Conclusão: As adolescentes atingiram o pico de massa óssea durante essa fase da vida. Duas formulações de contraceptivos hormonais orais de baixa dosagem, após um ano de uso, se associaram a menor incremento na densidade mineral óssea e menor concentração de marcadores de formação óssea quando confrontados com resultados de adolescentes não usuárias de contraceptivos.

Rol de la osteocalcina más allá del hueso / Role of osteocalcin beyond bone

Los hallazgos osteológicos se intensi!caron en los últimos años. Se demostró que el esqueleto se comporta, además de sus funciones clásicas, como un órgano de secreción endocrina que sintetiza al menos dos hormonas: el factor de crecimiento de !broblastos 23 (FGF-23) y la osteocalcina (Ocn). La Ocn es un péptido pequeño que contiene 3 residuos de ácido glutámico. Estos residuos se carboxilan postraduccionalmente, quedando retenida en la matriz ósea. La forma decarboxilada en el primer residuo de ácido glutámico (GluOcn) fue reportada por poseer efectos biológicos; la resorción ósea es el mecanismo clave para su bioactivación. La presente revisión se centra en los conocimientos actuales sobre la función hormonal de la Ocn. A la fecha se reporta que la Ocn regularía el metabolismo energético aumentando la proliferación de células ` pancreáticas, y la secreción de insulina y de adiponectina. Sobre el músculo esquelético actuaría favoreciendo la absorción y el catabolismo de nutrientes. La función reproductiva masculina estaría regulada mediante el estímulo a las células de Leydig para sintetizar testosterona; en el desarrollo cerebral y la cognición, la Ocn aumentaría la síntesis de neurotransmisores monoaminados y disminuiría el neurotransmisor inhibidor GABA. Si bien son indispensables mayores evidencias para dilucidar los mecanismos reguladores por medio de los cuales actuaría la Ocn, los resultados enumerados en los distintos estudios experimentales establecen la importancia de este novedoso integrante molecular. Dilucidar su rol dentro de estos procesos interrelacionados en seres humanos abriría la posibilidad de utilizar a la Ocn en el tratamiento de enfermedades endocrino-metabólicas. (AU)

Osteological !ndings have intensi!ed in recent years. The skeleton behaves as an endocrine secretion organ that synthesizes at least two hormones: osteocalcin (Ocn) and !broblast growth factor 23 (FGF-23). Ocn is a small peptide that contains 3 glutamic acid residues. After translation, these residues are carboxylated to make possible its retention into the bone matrix. Decarboxylation on the !rst glutamic acid residue (GluOcn) has been reported to have biological effects. Bone resorption is the key mechanism for its bioactivation. This review focuses on current knowledge on Ocn hormonal function. It has been reported that Ocn regulates energy metabolism by increasing the proliferation of pancreatic ` cells, and the secretion of insulin and adiponectin. On the skeletal muscle, it may act by favoring the absorption and catabolism of nutrients. Male reproductive function might be regulated by stimulating Leydig cells to synthesize testosterone. Regarding brain development and cognition, Ocn would increase monoamine neurotransmitters synthesis and decrease inhibitory neurotransmitter GABA. Although more evidence is needed to elucidate the regulatory mechanisms of Ocn, different experimental studies establish the importance of this novel molecular mediator. Clarifying its role within interrelated processes in humans, might open the possibility of using Ocn in different treatments of endocrine-metabolic diseases. (AU)

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives.

OBJECTIVE: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. METHODS: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n=42) (20µg EE/150µg desogestrel), oral contraceptives 2 (n=66) (30µg EE/3mg drospirenone), and a control group (n=70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. RESULTS: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. CONCLUSION: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Osteocalcin levels in a healthy population of western Mexico and comparison with populations from around the world. / Niveles de referencia de osteocalcina en población sana de México.

Introduction: Osteocalcin has been shown to have an inverse relationship with blood glucose, insulin resistance and adiposity. Objective: To determine osteocalcin normal serum concentration in Mexican healthy adults and compare it with values reported in other populations. Method: Carboxylated and undercarboxylated osteocalcin serum concentrations were determined in 100 healthy adults by means of enzyme immunoassay; osteocalcin total concentration was calculated. A descriptive comparison was made with other populations' values reported in the literature. Results: Carboxylated and undercarboxylated osteocalcin median concentrations were 3.22 ng/mL and 1.61 ng/mL, respectively. Mean total osteocalcin was 7.40 ± 5.11 ng/mL. There was no significant difference between the osteocalcin values in our population and those of populations where similar quantification methods to ours were used. Conclusion: Osteocalcin total serum concentration mean in the analyzed population was 7.40 ng/mL. There are subtle variations between populations that are attributable to genetic and population factors; however, the quantification method was the only variable that was shown to significantly influence on osteocalcin levels in healthy populations.

Introducción: Se ha demostrado que la osteocalcina tiene una relación inversa con la glucemia, resistencia a la insulina y adiposidad. Objetivo: Determinar la concentración sérica normal de osteocalcina en adultos sanos mexicanos y compararlos con los reportados en otras poblaciones. Método: Se determinó la concentración sérica de osteocalcina carboxilada y pobremente carboxilada en 100 adultos sanos mediante inmunoensayo enzimático; se calculó la concentración de osteocalcina total. Se hizo una comparación descriptiva con valores de otras poblaciones reportadas en la literatura. Resultados: Las medianas de las concentraciones de osteocalcina carboxilada y pobremente carboxilada fueron 3.22 ng/mL y 1.61 ng/mL, respectivamente; la media de osteocalcina total fue 7.40 ± 5.11 ng/mL. No hubo diferencia significativa entre los valores de osteocalcina total en nuestra población y los de poblaciones en las que se utilizaron métodos de cuantificación similares al nuestro. Conclusión: La concentración sérica promedio de osteocalcina total en la población analizada fue de 7.40 ng/mL. Las variaciones sutiles entre poblaciones son atribuibles a factores genéticos y poblacionales, sin embargo, el método de cuantificación fue el único que se comprobó influye significativamente en los niveles de osteocalcina en poblaciones sanas.

Prevalencia de deficiencia de vitamina K y factores asociados en pacientes con fibrosis quística sin aporte suplementario / Prevalence of vitamin K deficiency and associated factors in non-supplemented cystic fibrosis patients

Introducción. La deficiencia de vitamina K es prevalente en pacientes con fibrosis quística (FQ) aun con aporte suplementario. Se desconocen factores de riesgo fiables para determinar su ocurrencia. Nuestro objetivo fue evaluar la prevalencia de deficiencia de vitamina K y factores asociados en los pacientes con FQ que no recibían aporte suplementario. Métodos. Se determinaron protrombina inducida por ausencia de vitamina K (PIVKA-II) y osteocalcina infracarboxilada (OCic). Se evaluó el estado clínico y su relación con la deficiencia de vitamina K. El análisis estadístico incluyó prueba de Mann-Whitney, ANOVA o Kruskal-Wallis, prueba χ² o prueba de Fisher-Freeman-Halton y regresión logística múltiple lineal y escalonada hacia adelante. Resultados. Se incluyeron 79 pacientes con FQ de entre 0,4-25,3 años. Se observaron valores anómalos de PIVKA-II y OCic en 56 (70,9%) y 45 (57,0%) pacientes. Los pacientes con PIVKA-II elevada eran significativamente mayores (p = 0,0184) y tenían puntajes Z de peso corporal (p= 0,0297) inferiores a los pacientes que tenían concentraciones normales. No se hallaron diferencias entre los pacientes con OCic normal o patológica. Se notificaron valores anómalos de PIVKA-II y OCic más frecuentemente en pacientes con dos mutaciones graves en el gen CFTR y con un estado nutricional malo/deficiente. Los análisis de regresión múltiple lineal y de regresión múltiple escalonada hacia adelante no revelaron factores predictivos sólidos para determinar la deficiencia de vitamina K. Conclusión. La deficiencia de vitamina K es altamente prevalente durante la evolución natural de la fibrosis quística. No se hallaron determinantes clínicos fiables para precisar su ocurrencia.

Introduction. Vitamin K deficiency is highly prevalent in cystic fibrosis (CF) patients despite supplementation. Moreover, no reliable risk factors for its occurrence are known. The aim was to assess the prevalence of vitamin K deficiency and associated factors in non-supplemented CF patients. Methods. Prothrombin concentration induced by vitamin K absence (PIVKA-II) and the undercarboxylated osteocalcin percentage (u-OC) were determined. In all patients clinical status was assessed and its relation to vitamin K deficiency determined. The following tests were used for statistical analysis: Mann-Whitney test, ANOVA test or the Kruskal Wallis test, the chi-squared test or the Fisher-Freeman-Halton test, and multiple linear and multiple forward stepwise logistic regression analysis. Results. The study group comprised 79 CF patients aged 0.4-25.3 years. PIVKA-II and u-OC were abnormal in 56 (70.9%) and 45 (57.0%) patients. Patients with elevated PIVKA-II were significantly older (p= 0.0184) and had lower Z-score values for body weight (p= 0.0297) than those with normal concentrations. Patients with normal or pathological u-OC percentage did not differ. Abnormal PIVKA-II and u-OC were reported more frequently in subjects with two severe CFTR mutations and with worse/poor nutritional status. Multiple linear and forward stepwise regression analyses did not reveal strong predictive factors of vitamin K deficiency. Conclusion. Vitamin K deficiency is highly prevalent in the natural course of cystic fibrosis. There are no reliable clinical determinants of its occurrence.

El esqueleto como órgano endocrino: funciones metabólicas de la osteocalcina / The skeleton as an endocrine organ: metabolic functions of osteocalcin

El esqueleto es uno de los sistemas más grandes de un vertebrado y, como tal, es razonable especular que no puede funcionar aislado del resto del organismo. De hecho, sabemos que existen sistemas complejos de regulación cruzada entre el esqueleto y muchos otros órganos. Hoy poseemos herramientas que nos permiten realizar supresión genética en células o tejidos específicos. Esto nos ha permitido comprender cómo los órganos se comunican entre sí y ha revitalizado el concepto de fisiología del organismo como un todo. Efectivamente, los últimos años han sido testigos del descubrimiento de funciones inesperadas que ejerce el esqueleto y que afectan al organismo en su totalidad. Una de tales funciones reconocidas recientemente es el control del metabolismo energético, a través de la secreción de osteocalcina. La osteocalcina es una hormona producida por los osteoblastos que regula la secreción de insulina, la sensibilidad a esta hormona y el metabolismo energético. Los hallazgos iniciales suscitaron varias preguntas fundamentales sobre la naturaleza de la acción de la insulina sobre el hueso. Pero esto solo fue la punta del iceberg. Efectivamente, más adelante se descubrió, mediante el análisis de ratones que carecen del receptor de insulina (Ins R) solamente en osteoblastos, que la acción de la insulina sobre estas células favorecía la homeostasis de la glucosa en todo el cuerpo. Es importante destacar que esta función de la insulina en los osteoblastos opera mediante la regulación negativa de la carboxilación y la biodisponibilidad de la osteocalcina. Más aún, se observó que las vías de señalización de la insulina en los osteoblastos regulan positivamente no solo la formación sino también la resorción del hueso. Curiosamente, parece que las vías de señalización de la insulina en osteoblastos pueden inducir la activación de la osteocalcina mediante la estimulación de la actividad de los osteoclastos. De hecho, el bajo pH generado durante la resorción ósea es suficiente para desencadenar la descarboxilación (y subsiguiente activación) de la osteocalcina. En breve discutiremos dos nuevas proposiciones: 1) los osteoblastos son un blanco utilizado por la insulina para controlar la homeostasis de la glucosa en todo el organismo y 2) la resorción ósea desempeña un papel fundamental en la regulación de la activación de la osteocalcina. (AU)

The skeleton is one of the biggest systems in a vertebrate animal and, as such, it is reasonable to speculate that it cannot function isolated from the rest of the organism. In fact, we know that complex systems exist for the cross-regulation between the skeleton and several other organs. Today, we have the tools that allow us to perform genetic suppression in specific cells or tissues. This has allow us understand the mechanisms by which the organs communicate with each other and has revitalized the concept of organismal physiology as a whole. Studies conducted in recent years have uncovered unexpected functions performed by the skeleton. One of these is the control of global energy metabolism, through the secretion of osteocalcin, a protein produced by osteoblasts that acts as a hormone regulating insulin secretion, insulin sensitivity and energy expenditure. The evidence comes from the analysis of mice lacking insulin receptor (InsR) exclusively in osteoblasts. These mice have a global metabolic phenotype demonstrating that the action of insulin in osteoblasts promotes the homeostasis of glucose throughout the body. This action of insulin in osteoblasts is mediated by the negative regulation of the carboxylation (and bioavailability) of osteocalcin. The decarboxylation (and activation) of osteocalcin, in turn, occurs in the osteoclastic resorption pit. Briefly: the osteoblast is a target used by insulin to control the homeostasis of glucose throughout the body and bone resorption is the mechanism that regulates the activation of osteocalcin. (AU)

Viabilidade da mensuração de marcadores de remodelação óssea em mulheres com lúpus eritematoso sistêmico / Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus

Objetivo: Investigar a viabilidade dos marcadores de remodelação óssea (MRO) na avaliação do metabolismo ósseo em pacientes com lúpus eritematoso sistêmico (LES), de acordo com as diretrizes da International Osteoporosis Foundation e da International Federation of Clinical Chemistry and Laboratory Medicine. Métodos: O estudo incluiu 43 pacientes do sexo feminino com LES. Foram medidos os níveis séricos de propeptídeo N-terminal do procolágeno tipo I (PINP), telopeptídeo C-terminal do colágeno tipo I (CTX), osteocalcina, HPT, 25(OH)D, anticorpos anticardiolipina, antidsDNA e antinucleossomo. Resultados: Os níveis de PINP e CTX estavam elevados em pacientes com LES com idade > 45, em comparação com aqueles com idade < 45 anos, embora com significância estatística limítrofe (p = 0,05). Foram encontradas correlações entre os MRO: a mais forte foi entre o PINP e a osteocalcina (τ = 0,69, p < 0,05). Encontrou-se que o PINP e a osteocalcina estão correlacionados com o HPT (τ = 0,3, τ = 0,29, respectivamente, p < 0,05). A idade estava correlacionada com o PINP (τ = 0,23, p < 0,05). Valores elevados de PINP foram encontrados em maior frequência do que valores elevados de osteocalcina ou CTX, tanto em pacientes com idade < 45 (p = 0,001) quanto > 45 (p < 0,001). Não houve diferença estatisticamente significativa nos níveis de PINP, osteocalcina ou CTX com relação à estação do ano, nem em todo o grupo de pacientes com LES, nem naqueles com mais ou menos de 45 anos. O uso prévio de glucocorticoides não esteve associado a diferenças nos MRO. Conclusões: O aumento nos MRO no LES parece refletir predominantemente o padrão de remodelação óssea relacionado com a idade. Pode-se esperar que o PINP aumentado seja o desfecho mais comumente encontrado entre os MRO. É necessário incluir melhores diagnósticos de distúrbios ósseos com MRO, feitos de acordo com as normas internacionais de referência, na abordagem de ...

Objective: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. Methods: The study included 43 female SLE patients. Serum pro-collagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. Results: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ= 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ= 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. Conclusions: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment. .

Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. METHODS: The study included 43 female SLE patients. Serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. RESULTS: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ = 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ = 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. CONCLUSIONS: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment.

Osteoclacin expression during autogenous onlay bone grafts with or without resorbable collagen membrane in diabetic rats / Expressão da osteocalcina no reparo de enxertos ósseos autógenos onlay recobertos ou não por membrana colágena reabsorvível em ratos diabéticos

Objetivo: O objetivo deste estudo foi quantificar, através da técnica imunoistoquímica, a expressão do marcador de formação óssea Osteocalcina no processo de reparo do enxerto ósseo autógeno onlay, associado ou não à membrana colágena reabsorvível e comparar esses achados com a presença da Diabetes Mellitus. Material e Métodos: Foram utilizados 60 ratos (Rattus norvegicus, variação albinus, Wistar) com 90 dias de idade, divididos em dois grupos , cada um contendo 30 animais: Grupo Teste com Diabéticos , composto por ratos com diabetes induzida e Grupo Controle composto por ratos normoglicêmicos. Todos receberam enxertos na hemi mandíbula esquerda com recobrimento de membrana colágena e na hemi mandíbula direita sem recobrimento. Os animais foram eutanasiados nos períodos 0h, 7, 14, 21, 45 e 60 dias. A análise imunoistoquímica foi realizada com o marcador Osteocalcina na interface leito-enxerto. Para analise da expressão imunoistoquímica da Osteocalcina, realizou-se uma fotografia com visão panorâmica do enxerto e duas fotografias em maior aumento. Resultados: Os resultados mostraram que houve diferença estatisticamente significante ao nível de 5% intragrupo para Diabético e Controle com e sem membrana e também quando comparamos o grupo Diabético com o Controle com a presença da membrana. Conclusão: Dentro dos limites do presente estudo, pode-se concluir que a marcação da osteocalcina pode sofrer alguma influência do diabetes, sendo expressa de forma mais tardia na presença dessa condição. Porém, a associação da membrana ao enxerto pode melhorar esse atraso e deixar a expressão semelhante ao grupo controle.

Objective: This study aimed to quantify through immunohistochemistry the expression of bone formation marker osteocalcin during the repair process of autogenous onlay bone graft, associated or not to the resorbable collagen membrane and to compare these findings with the presence of Diabetes Mellitus. Material and Methods: Sixty rats (Rattus norvegicus, albinus variation, Wistar) aged 90 days, were divided into two groups with 30 animals: test group – rats with induced diabetes; control group - normoglycemic rats. All rats received grafts on the left and right hemi-mandible with or without collagen membrane coverage, respectively. The animals were euthanized at the following periods: 0h, 7, 14, 21, 45, and 60 days. Immunohistochemistry analysis was performed by the marker osteocalcin at receptor site-graft interface. To analyze osteocalcin immunohistochemical expression, a panoramic view photograph of the graft was taken followed by two photographs at larger magnification. Results: No statistically significances at 5% level were observed between diabetic and control group with and without membrane; and diabetic and control groups with membrane coverage. Conclusion: Within the limits of this present study, it can be concluded that the osteocalcin marker might be influenced by diabetes so that it was late expressed during this condition. However, the association of the graft with the membrane could improve this delay by reaching expression values similar to those of control group.

Efeito do tratamento periodontal nos níveis de osteocalcina sérica em pacientes com diabetes tipo 2 e periodontite crônica severa / Effect of periodontal therapy on serum osteocalcin levels in patients with type 2 diabetes and severe chronic periodontitis

O tecido ósseo é metabolicamente ativo e sofre um processo contínuo de renovação e remodelação. A osteocalcina é um peptídeo secretado pelos osteoblastos. Apesar de ser primariamente depositada na matriz óssea recém-formada, uma pequena fração entra em circulação na corrente sanguínea, sendo considerada como um marcador de formação óssea e interferir na homeostasia da glicose. O objetivo deste estudo foi investigar se o tratamento periodontal afeta os níveis séricos de osteocalcina em pacientes com DM2 e periodontite crônica severa. 26 pacientes foram divididos em grupo teste (n=13, idade média de 55,8 ± 8,4 anos, 9 homens e 4 mulheres) e controle. (n=13, idade média de 59,4± 8.4, 5 homens e 8 mulheres). O grupo teste recebeu tratamento periodontal e grupo controle nãorecebeu tratamento periodontal imediato. O exame periodontal incluiu medidas de IP (Índice de placa), SS (Sangramento à sondagem), PBS (Profundidade de bolsa à sondagem), NIC (Nível de inserção clínica). Exames laboratoriais incluíram HBA1c, glicemia estimada, glicose, triglicerídeo, colesterol total e frações. A concentração de osteocalcina sérica foi analisada pelo ELISA. O exame periodontal, exames laboratoriais e concentração de osteocalcina foram reavaliados 90 dias após. Os resultados mostraram que não houve alterações significativas nos parâmetros periodontais, exames laboratoriais, e níveis de osteocalcina 90 dias após o tratamento periodontal. Conclusão: o tratamento periodotnal não influenciou nos níveis séricos da osteocalcina em pacientes com diabetes melllitus tipo 2 e periodontite crônica severa.

Bone tissue is metabolically active and undergoes a continuous process of resorption and formation. Osteocalcin is a peptide secreted by osteoblasts. Although primarily deposited in newly formed bone matrix, a small fraction enters into circulation in the bloodstream and is considered as a marker of bone formation and interferes with glucose homeostasis. The aim of this study was to investigate whether periodontal treatment affects serum osteocalcin levels in patients with type 2 diabetes and severe chronic periodontitis. 26 patients were divided into test group (n = 13, mean age 55.8 ± 8.4 years, 9 men and 4 women) and control. (n = 13, mean age 59.4 ± 8.4, 5 men and 8 women). The test group received periodontal treatment and untreated control group. Periodontal examination included PI measures (plaque index), BOP (bleeding on probing), PPD (probing pocket depth), CAL (clinical attachment level). Laboratory tests included HbA1c, glucose, triglyceride, total cholesterol and fractions. The concentration of serum osteocalcin was analyzed by ELISA. Periodontal examination, laboratory tests and concentration of osteocalcin were reassessed after 90 days. The results showed no significant changes in periodontal parameters, laboratory tests, and osteocalcin levels 90 days after periodontal treatment. In conclusion, periodontal treatment did not influence the serum levels of osteocalcin in patients with type 2 diabetes and severe chronic periodontitis.

Relationship between chronological and bone ages and pubertal stage of breasts with bone biomarkers and bone mineral density in adolescents / Relação entre as idades cronológica e óssea e o estágio puberal das mamas com os biomarcadores ósseos e a densidade mineral óssea em adolescentes

OBJECTIVE: To study bone mineral density (BMD) in adolescent females according to five groups of chronological age (CA), bone age (BA), and breast development stage (B), and to correlate these parameters with plasma bone biomarkers (BB). METHODS: This was a cross-sectional study performed in 101 healthy adolescent females between 10 and 20 years old. The study variables were: weight, height, body mass index (BMI), CA, B, BA, calcium intake, BMD, and BB. Osteocalcin (OC), bone alkaline phosphatase (BAP), and C-terminal telopeptide (S-CTx) were evaluated for BB. BMD was measured using dual energy X-ray absorptiometry (DXA). RESULTS: BMD in lumbar spine, proximal femur, and total body increased with age, and the respective observed averages were: in CA1 (10 years old), 0.631, 0.692, 0.798 g/cm2; in CA2 (11 to 12 years old), 0.698, 0.763, 0.840 g/cm2; in CA3 (13 to 14 years old), 0.865, 0.889, 0.972 g/cm2; in CA4 (15 to 16 years old), 0.902, 0.922, 1.013 g/cm2; and in CA5 (17 to 19 years old), 0.944, 0.929, 1.35 g/cm2. These results showed significant differences between 13 and 14 years of age (CA3) or when girls reached the B3 stage (0.709, 0.832, 0.867 g/cm2). The highest median concentrations of BB were between 10 and 12 years of age when adolescents were in the B2-B3 (p < 0.001). Median BB concentrations decreased in advanced BA and B. CONCLUSIONS: BB concentrations were positively correlated with the peak height velocity and negatively correlated with BMD in the study sites. Increased BMD and BB concentrations were observed in B3. .

OBJETIVO: Avaliar a densidade mineral óssea (DMO) em adolescentes do sexo feminino de acordo com a idade cronológica (IC), idade óssea (IO) e desenvolvimento das mamas (M) e suas correlações com biomarcadores de remodelação óssea em plasma (BO). MÉTODOS: Este foi um estudo transversal prospectivo feito em 101 adolescentes saudáveis do sexo feminino com idade entre 10 e 20 anos. As variáveis estudadas foram: peso, altura, índice de massa corpórea (IMC), IC, IO, M, ingestão de cálcio, DMO e BO. A osteocalcina (OC), fosfatase alcalina óssea (BAP) e o telopeptídeo C terminal (S-CTx) foram os biomarcadores de remodelação óssea avaliados. A DMO foi obtida por absorciometria de raios-X de dupla energia (DXA). RESULTADOS: A DMO de coluna lombar, fêmur proximal e corpo total aumentou com a idade, e as respectivas médias observadas foram: IC1 = 0,631, 0.692, 0,798 g/cm2; IC2, 0,698, 0,763, 0,840 g/cm2; IC3, 0,865, 0,889, 0,972 g/cm2; IC4, 0,902, 0,922, 1,013 g/cm2; e IC5, 0,944, 0,929, 1,35 g/cm2. Observou-se diferença significativa entre 13 e 14 anos (IC3) ou quando as meninas estavam em M3 (0,709, 0,832, 0,867 g/cm2). Os valores dos BO apresentaram elevação entre 10 e 12 anos e quando as adolescentes estavam em M2-M3 (p < 0,001). Os valores das medianas dos BO diminuíram com o avançar da IO e M. CONCLUSÕES: Os BOs mostraram paralelismo com o pico de velocidade de crescimento e demonstraram correlação negativa com a DMO no sítios avaliados. O aumento da DMO e dos BOs foi observado em M3. .

Relationship between chronological and bone ages and pubertal stage of breasts with bone biomarkers and bone mineral density in adolescents.

OBJECTIVE: To study bone mineral density (BMD) in adolescent females according to five groups of chronological age (CA), bone age (BA), and breast development stage (B), and to correlate these parameters with plasma bone biomarkers (BB). METHODS: This was a cross-sectional study performed in 101 healthy adolescent females between 10 and 20 years old. The study variables were: weight, height, body mass index (BMI), CA, B, BA, calcium intake, BMD, and BB. Osteocalcin (OC), bone alkaline phosphatase (BAP), and C-terminal telopeptide (S-CTx) were evaluated for BB. BMD was measured using dual energy X-ray absorptiometry (DXA). RESULTS: BMD in lumbar spine, proximal femur, and total body increased with age, and the respective observed averages were: in CA1 (10 years old), 0.631, 0.692, 0.798 g/cm(2); in CA2 (11 to 12 years old), 0.698, 0.763, 0.840 g/cm(2); in CA3 (13 to 14 years old), 0.865, 0.889, 0.972 g/cm(2); in CA4 (15 to 16 years old), 0.902, 0.922, 1.013 g/cm(2); and in CA5 (17 to 19 years old), 0.944, 0.929, 1.35 g/cm(2). These results showed significant differences between 13 and 14 years of age (CA3) or when girls reached the B3 stage (0.709, 0.832, 0.867 g/cm(2)). The highest median concentrations of BB were between 10 and 12 years of age when adolescents were in the B2-B3 (p<0.001). Median BB concentrations decreased in advanced BA and B. CONCLUSIONS: BB concentrations were positively correlated with the peak height velocity and negatively correlated with BMD in the study sites. Increased BMD and BB concentrations were observed in B3.

Osteocalcin, energy and glucose metabolism / Osteocalcina, metabolismo energético e da glicose

Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome.

A osteocalcina é uma proteína da matriz óssea que tem sido implicada com várias ações hormonais relacionadas à homeostase de glicose e ao metabolismo energético. Modelos animais e experimentais têm demonstrado que a osteocalcina é liberada do osso para a circulação sanguínea e age nas células betapancreáticas e no tecido adiposo. A osteocalcina decarboxilada é a isoforma hormonalmente ativa e estimula a secreção e sensibilidade à insulina no tecido adiposo e muscular. A insulina e a leptina, por sua vez, atuam no tecido ósseo modulando a secreção da osteocalcina, formando uma alça de retroalimentação tradicional em que o esqueleto torna-se um órgão endócrino. Novos estudos ainda são necessários para elucidar o papel da osteocalcina na regulação glicêmica e no metabolismo energético em humanos, com potenciais implicações terapêuticas no tratamento de diabetes, obesidade e síndrome metabólica.