Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado

Detalhes bibliográficos
Autor(a) principal: Cebrian, Cinthia Faraco Martinez
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Universitário da Ânima (RUNA)
Texto Completo: https://repositorio.animaeducacao.com.br/handle/ANIMA/3091
Resumo: Introduction: Osteogenesis imperfecta (OI) is a rare, congenital and hereditary disease. The main clinical feature is bone fragility; however, pain is also common, limits daily activities and affects quality of life. Supplementation with vitamin C is a possibility of complementary treatment that can contribute to the improvement of the symptoms of OI, since it is essential for the hydroxylation of proline during the synthesis of collagen, besides having already established anti-inflammatory function. Objectives: To evaluate the effect of supplementation with vitamin C or placebo on pain, quality of life, inflammation, collagen synthesis, bone turnover and fractures in children with IO in the use of pamidronate disodium. Methods: Randomized, double-blind, placebo-controlled pilot trial. After recruitment and evaluation of eligibility criteria, 54 children were randomized to receive either Placebo or Vitamin C supplementation. All evaluations were performed pre- and post-supplementation. The number of fractures was evaluated by chart analysis. Pain was assessed using the Face, Legs, Activity, Cry, Consolability (FLACC), Pain Scale-Revised (FPS-R) and Adolescent Pediatric Pain Tool (APPT) scales, appropriate for each age group. The questionnaires used to assess quality of life were the PedsQLTM Infant Scales and the PedsQLTM 4.0 Generic Core Scales. Serum concentrations of pro-inflammatory cytokines (TNF, IL-1β, IL-6 and MMP-9) and anti-inflammatory cytokines (IL-4 and IL-10), as well as TGF-β used as a marker of bone turnover, were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The measurement of serum hydroxyproline concentration was performed by colorimetric reaction. Results: Vitamin C supplementation did not alter the number of fractures and the quality of life. The pain was present in only one child and was not altered with supplementation. Vitamin C did not alter serum levels of TNF, IL-1β, IL-6 and MMP-9. Serum IL-4 levels did not change, but an increase in IL-10 concentration was observed after vitamin C supplementation over baseline levels, whereas the placebo-supplemented group reduced post-supplementation serum levels (P = 0.0023). In addition, the Vitamin C group presented a higher concentration of hydroxyproline in relation to the Placebo group (P = 0.013) after supplementation. In the temporal analysis, the group supplemented with vitamin C increased serum hydroxyproline levels from baseline, whereas in the placebo group, serum levels decreased (P = 0.0005). Serum TGF-β1 levels did not change with supplementation. Conclusion: Vitamin C is associated with elevated serum levels of IL-10, an anti-inflammatory cytokine capable of reducing osteoclast activity. In addition to increasing serum levels of hydroxyproline, which may be due to increased production of collagen, a vitamin C dependent reaction. This can be understood as an improvement factor since the basic defect of OI lies in the production of collagen type I.
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spelling Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizadoOsteogênese ImperfeitaVitamina CDorQualidade de vidaColágenoCitocinasHidroxiprolinaIntroduction: Osteogenesis imperfecta (OI) is a rare, congenital and hereditary disease. The main clinical feature is bone fragility; however, pain is also common, limits daily activities and affects quality of life. Supplementation with vitamin C is a possibility of complementary treatment that can contribute to the improvement of the symptoms of OI, since it is essential for the hydroxylation of proline during the synthesis of collagen, besides having already established anti-inflammatory function. Objectives: To evaluate the effect of supplementation with vitamin C or placebo on pain, quality of life, inflammation, collagen synthesis, bone turnover and fractures in children with IO in the use of pamidronate disodium. Methods: Randomized, double-blind, placebo-controlled pilot trial. After recruitment and evaluation of eligibility criteria, 54 children were randomized to receive either Placebo or Vitamin C supplementation. All evaluations were performed pre- and post-supplementation. The number of fractures was evaluated by chart analysis. Pain was assessed using the Face, Legs, Activity, Cry, Consolability (FLACC), Pain Scale-Revised (FPS-R) and Adolescent Pediatric Pain Tool (APPT) scales, appropriate for each age group. The questionnaires used to assess quality of life were the PedsQLTM Infant Scales and the PedsQLTM 4.0 Generic Core Scales. Serum concentrations of pro-inflammatory cytokines (TNF, IL-1β, IL-6 and MMP-9) and anti-inflammatory cytokines (IL-4 and IL-10), as well as TGF-β used as a marker of bone turnover, were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The measurement of serum hydroxyproline concentration was performed by colorimetric reaction. Results: Vitamin C supplementation did not alter the number of fractures and the quality of life. The pain was present in only one child and was not altered with supplementation. Vitamin C did not alter serum levels of TNF, IL-1β, IL-6 and MMP-9. Serum IL-4 levels did not change, but an increase in IL-10 concentration was observed after vitamin C supplementation over baseline levels, whereas the placebo-supplemented group reduced post-supplementation serum levels (P = 0.0023). In addition, the Vitamin C group presented a higher concentration of hydroxyproline in relation to the Placebo group (P = 0.013) after supplementation. In the temporal analysis, the group supplemented with vitamin C increased serum hydroxyproline levels from baseline, whereas in the placebo group, serum levels decreased (P = 0.0005). Serum TGF-β1 levels did not change with supplementation. Conclusion: Vitamin C is associated with elevated serum levels of IL-10, an anti-inflammatory cytokine capable of reducing osteoclast activity. In addition to increasing serum levels of hydroxyproline, which may be due to increased production of collagen, a vitamin C dependent reaction. This can be understood as an improvement factor since the basic defect of OI lies in the production of collagen type I.Introdução: A Osteogênese Imperfeita (OI) é uma doença rara, congênita e hereditária. A principal característica clínica é a fragilidade óssea, no entanto, a dor também é comum, limita as atividades diárias e afeta a qualidade de vida. A suplementação com vitamina C é uma possibilidade de tratamento complementar que pode contribuir para a melhora dos sintomas da OI, visto que é essencial para a hidroxilação da prolina durante a formação do colágeno, além de ter função anti-inflamatória já estabelecida. Objetivos: Avaliar o efeito da suplementação com a vitamina C ou placebo sobre a dor, qualidade de vida, inflamação, síntese do colágeno, turnover ósseo e fraturas em crianças com OI em uso de pamidronato dissódico. Métodos: Estudo piloto de um ensaio clínico randomizado, duplo cego, controlado com placebo. Após o recrutamento e a avaliação dos critérios de elegibilidade, 54 crianças foram randomizadas para receber a suplementação com Placebo ou Vitamina C. Todas as avaliações foram realizadas pré e pós-suplementação. Avaliou-se o número de fraturas pela análise do prontuário. A dor foi avaliada com as escalas Face, Legs, Activity, Cry, Consolability (FLACC), Faces Pain Scale – Revised (FPS-R) e Adolescent Pediatric Pain Tool (APPT), adequadas a cada faixa etária. Os questionários utilizados para a avaliação da qualidade de vida foram o PedsQLTM Infant Scales e o PedsQLTM 4.0 Generic Core Scales. As análises das concentrações séricas das citocinas pró-inflamatórias (TNF, IL-1β, IL-6 e MMP-9) e anti-inflamatórias (IL-4 e IL-10), além dos níveis de TGF-β, utilizado como marcador do turnover ósseo, foram avaliados por Ensaio de Imunoabsorção Enzimática (ELISA). A mensuração da concentração sérica de hidroxiprolina foi realizada por reação colorimétrica. Resultados: A suplementação com vitamina C não alterou o número de fraturas e a qualidade de vida. A dor se mostrou presente em apenas uma criança e não foi alterada com a suplementação. A vitamina C não alterou os níveis séricos de TNF, IL-1β, IL-6 e MMP-9. Os níveis séricos de IL-4 não se alteraram, mas observou-se um aumento na concentração de IL-10 após a suplementação com vitamina C em relação aos níveis basais, enquanto o grupo suplementado com placebo reduziu os níveis séricos pós-suplementação (P=0,0023). Ademais, o grupo Vitamina C apresentou uma concentração maior de hidroxiprolina em relação ao grupo Placebo (P= 0,013) pós-suplementação. Na análise temporal, o grupo suplementado com vitamina C aumentou os níveis séricos de hidroxiprolina, em relação aos valores basais, enquanto que no grupo suplementado com placebo, os níveis séricos diminuíram (P= 0,0005). Os níveis séricos de TGF-β1 não se alteraram com a suplementação. Conclusão: A vitamina C está associada à elevação dos níveis séricos de IL-10, uma citocina anti-inflamatória capaz de reduzir a atividade dos osteoclastos. Além de aumentar os níveis séricos de hidroxiprolina, que pode ser decorrente do aumento da produção de colágeno, reação dependente da vitamina C. Isso pode ser entendido como um fator de melhora visto que o defeito básico da OI encontra-se na produção do colágeno tipo I.Bobinski, FrancianeCebrian, Cinthia Faraco Martinez2020-11-06T14:42:33Z2020-11-26T20:57:55Z2020-11-06T14:42:33Z2020-11-26T20:57:55Z2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis81 f.application/pdfhttps://repositorio.animaeducacao.com.br/handle/ANIMA/3091Programa de Pós-Graduação em Ciência da SaúdePalhoçaAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessporreponame:Repositório Universitário da Ânima (RUNA)instname:Ânima Educaçãoinstacron:Ânima2020-12-01T16:48:07Zoai:repositorio.animaeducacao.com.br:ANIMA/3091Repositório InstitucionalPRIhttps://repositorio.animaeducacao.com.br/oai/requestcontato@animaeducacao.com.bropendoar:2020-12-01T16:48:07Repositório Universitário da Ânima (RUNA) - Ânima Educaçãofalse
dc.title.none.fl_str_mv Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
title Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
spellingShingle Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
Cebrian, Cinthia Faraco Martinez
Osteogênese Imperfeita
Vitamina C
Dor
Qualidade de vida
Colágeno
Citocinas
Hidroxiprolina
title_short Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
title_full Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
title_fullStr Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
title_full_unstemmed Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
title_sort Suplementação com vitamina C em crianças com Osteogênese Imperfeita: estudo piloto de um ensaio clínico controlado e randomizado
author Cebrian, Cinthia Faraco Martinez
author_facet Cebrian, Cinthia Faraco Martinez
author_role author
dc.contributor.none.fl_str_mv Bobinski, Franciane
dc.contributor.author.fl_str_mv Cebrian, Cinthia Faraco Martinez
dc.subject.por.fl_str_mv Osteogênese Imperfeita
Vitamina C
Dor
Qualidade de vida
Colágeno
Citocinas
Hidroxiprolina
topic Osteogênese Imperfeita
Vitamina C
Dor
Qualidade de vida
Colágeno
Citocinas
Hidroxiprolina
description Introduction: Osteogenesis imperfecta (OI) is a rare, congenital and hereditary disease. The main clinical feature is bone fragility; however, pain is also common, limits daily activities and affects quality of life. Supplementation with vitamin C is a possibility of complementary treatment that can contribute to the improvement of the symptoms of OI, since it is essential for the hydroxylation of proline during the synthesis of collagen, besides having already established anti-inflammatory function. Objectives: To evaluate the effect of supplementation with vitamin C or placebo on pain, quality of life, inflammation, collagen synthesis, bone turnover and fractures in children with IO in the use of pamidronate disodium. Methods: Randomized, double-blind, placebo-controlled pilot trial. After recruitment and evaluation of eligibility criteria, 54 children were randomized to receive either Placebo or Vitamin C supplementation. All evaluations were performed pre- and post-supplementation. The number of fractures was evaluated by chart analysis. Pain was assessed using the Face, Legs, Activity, Cry, Consolability (FLACC), Pain Scale-Revised (FPS-R) and Adolescent Pediatric Pain Tool (APPT) scales, appropriate for each age group. The questionnaires used to assess quality of life were the PedsQLTM Infant Scales and the PedsQLTM 4.0 Generic Core Scales. Serum concentrations of pro-inflammatory cytokines (TNF, IL-1β, IL-6 and MMP-9) and anti-inflammatory cytokines (IL-4 and IL-10), as well as TGF-β used as a marker of bone turnover, were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The measurement of serum hydroxyproline concentration was performed by colorimetric reaction. Results: Vitamin C supplementation did not alter the number of fractures and the quality of life. The pain was present in only one child and was not altered with supplementation. Vitamin C did not alter serum levels of TNF, IL-1β, IL-6 and MMP-9. Serum IL-4 levels did not change, but an increase in IL-10 concentration was observed after vitamin C supplementation over baseline levels, whereas the placebo-supplemented group reduced post-supplementation serum levels (P = 0.0023). In addition, the Vitamin C group presented a higher concentration of hydroxyproline in relation to the Placebo group (P = 0.013) after supplementation. In the temporal analysis, the group supplemented with vitamin C increased serum hydroxyproline levels from baseline, whereas in the placebo group, serum levels decreased (P = 0.0005). Serum TGF-β1 levels did not change with supplementation. Conclusion: Vitamin C is associated with elevated serum levels of IL-10, an anti-inflammatory cytokine capable of reducing osteoclast activity. In addition to increasing serum levels of hydroxyproline, which may be due to increased production of collagen, a vitamin C dependent reaction. This can be understood as an improvement factor since the basic defect of OI lies in the production of collagen type I.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020-11-06T14:42:33Z
2020-11-26T20:57:55Z
2020-11-06T14:42:33Z
2020-11-26T20:57:55Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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language por
dc.relation.none.fl_str_mv Programa de Pós-Graduação em Ciência da Saúde
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nc-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nc-nd/3.0/br/
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