Comparação entre a densidade mineral óssea e marcadores ósseos de formação de adolescentes usuárias de duas formulações de anticoncepcionais hormonais orais de baixa dosagem: contraceptivo oral de baixa dosagem e densidade e marcadores ósseos.
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2017-02-03
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Rizzo, Anapaula da Conceição Bisi [UNESP]
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Universidade Estadual Paulista (Unesp)
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RESUMO Objetivo: Avaliar prospectivamente as repercussões sobre o metabolismo ósseo de adolescentes de 12 a 20 anos incompletos usuárias de anticoncepcional hormonal oral de baixa dosagem (ACO), contendo EE 20 µg/Desogestrel 150 µg ou EE 30 μg/Drospirenona 3 mg, por período de um ano, confrontando os resultados aos obtidos entre adolescentes saudáveis não usuárias de ACO. Casuística e Métodos: Trata-se de um estudo quase experimental. As adolescentes incluídas foram divididas em três grupos: grupo ACO1 (EE 20µg/Desogestrel 150 µg) composto por 42 adolescentes, grupo ACO2 (EE 30 μg/ Drospirenona 3 mg) com 66 participantes e 70 que compuseram o grupo controle. Todas as adolescentes no momento de inclusão foram submetidas à avaliação antropométrica, densitométrica (DXA), obtendo-se densidade (DMO) e conteúdo mineral ósseo (CMO) de coluna lombar, corpo total e subtotal, massa magra, massa de gordura e % de gordura, realizado RX de idade óssea. Foram convidadas para a coleta sanguínea, obtendo-se os marcadores de formação óssea, osteocalcina (OC) e fosfatase alcalina óssea FAO). Após 12 meses de uso dos ACOs, as adolescentes foram submetidas a nova avaliação semelhante à do momento inicial e solicitação de dosagem de β Estradiol, após seis meses de uso dos contraceptivos. Para a comparação entre as variáveis dos grupos de não usuárias e usuárias de ACO1 e ACO2, no momento basal, utilizou-se o teste de Kruskal Wallis e, para a comparação entre os grupos ACO1 e ACO2, na linha de base, o teste de Mann-Whitney foi utilizado. Tanto no momento basal, como na comparação momento basal e 12 meses de uso dos ACOs, o teste de Wilcoxon, fixado o nível de significância em 5%. Para estudar o efeito da idade sobre as variáveis nutricionais, densitométricas e sobre as concentrações dos marcadores ósseos nas adolescentes não usuárias de contraceptivos (controles), realizou-se Análise de Regressão Linear. Para todos os testes aceitou-se significância quando p<0,05. Resultados: No momento inicial do estudo, não foi observada diferença estatísticamente significaticativa em relação às variáveis analisadas entre os grupos ACO1, ACO2 e controle, à exceção do percentual de gordura corporal, quando as adolescentes do grupo ACO2 diferiram das controles e do grupo ACO1. Pela análise da Regressão Linear Simples evidenciou-se que, para estudar o efeito de todos os indicadores em função da idade, no grupo controle, para cada ano de idade cronológica a mais, encontrou-se um acréscimo na idade óssea de 1,04 anos, 3,42 kg de peso, 1,33 kg/m² de IMC e, de 0,1m na altura. Quanto às variáveis densitométricas analisadas, constatou-se diferenças estatísticas significativas nas DMO de coluna lombar, corpo total e subtotal, com acréscimo de 0,06 g/cm² em cada ano a mais. Observou-se acréscimos nos CMO de coluna lombar, corpo total e subtotal, de 3,22g, 117,21g e 89,36g respectivamente, com diferenças significativas, p <0,001. Quanto à massa de gordura e massa magra, também houve incremento. No tocante aos marcadores de formação óssea (FAO, OC) constatou-se uma redução na concentração da FAO de - 5,19U/L, estatísticamente significante. Em relação à OC, não houve diferença significativa. Quando as medianas das variáveis antropométricas, densitométricas ósseas, de composição corporal e as concentrações dos marcadores ósseos FAO e OC obtidas no momento basal foram confrontadas às obtidas após 12 meses, entre adolescentes expostas às duas formulações de ACO, observou-se que houve diferença estatística em relação à idade cronológica e a idade óssea. Quanto às demais variáveis analisadas, constataram-se diferenças significativas entre as variáveis antropométricas peso e IMC, nos dois grupos e, na estatura para o grupo ACO2 e, não se observou diferenças para o percentil do IMC e escore z de IMC. Quanto às variáveis obtidas pela DXA, nos diversos sítios analisados, na comparação momento basal e um ano, entre as usuárias de ACOs, não se constatou diferenças significativas para DMO e CMO lombar, DMO e CMO corpo total e DMO e CMO subtotal para o grupo ACO2 e de todas as mesmas variáveis, a exceção do CMO de corpo total para o grupo ACO1, p=0,001. No tocante às concentrações dos biomarcadores de formação óssea (FAO, OC), verificou-se uma redução nas medianas da FAO na comparação momento basal frente a um ano de uso no ACO1 e ACO2, com diferença significativa, p=0,040 e p<0,001. Reduções nas concentrações de osteocalcina também puderam ser observadas 12 meses após, no grupo ACO1, p=0,002, e no ACO2, p<0,001. Conclusão: O uso das duas formulações de contraceptivos hormonais orais de baixa dosagem, após um ano de seguimento, se associa a efeitos negativos sobre a massa óssea, com incrementos na densidade e conteúdo mineral ósseo aquém daquele evidenciado para essa faixa etária e com redução significativa das concentrações do marcadores ósseos de formação (FAO e OC), quando os resultados são confrontados com os advindos de adolescentes controles não usuárias de contraceptivos.
Abstract. Objective: The objective of this study was to evaluate prospectively the repercussions on bone metabolism of incomplete adolescents from 12 to 20 years old, using oral low-dose hormonal contraceptive (COC), containing EE 20 μg/Desogestrel 150 μg or EE 30 μg Drospirenone 3 mg, for one year period, comparing the results to those obtained among healthy adolescents who did not use COC. Case study and methods: This was a quasi-experimental study The enclosed adolescents were divided into three groups: COC1 group (EE 20 μg Desogestrel 150 μg) compounded of 42 adolescents, COC2 group (EE 30 μg Drospirenone 3 mg) with 66 participants and 70 who composed the control group. All the adolescents at the moment of the inclusion were submitted to the anthropometric, densitrometric (DXA) evaluation, obtaining bone mineral density (BMD) and bone mineral content(BMC) of lumbar spine, total and subtotal body lean mass, fat mass and % fat, performed XR bone age. They were invited to the blood collection, obtaining markers of bone formation, osteocalcin (OC) and bone alkaline phosphatase. After 12 months of COCs use, the adolescents were submitted to a new similar evaluation to that one of the initial moment and request of β Estradiol dosage, after six months of contraceptive use. For the comparison between the variables of the non-users and users of COC1 and COC2 at baseline, the Krus Kal Wallis test was used and, for the comparison between the groups COC1 and COC2 at baseline, Mann-Whitney test was used. Either at baseline or in the comparison baseline, and 12 months of use of the COCs, the Wilcoxom test, set the level of significance at 5%. To study the effect of age on the nutritional variables, densitometric measurements and on the concentrations of bone markers in non-users adolescents of contraceptives (controls),Linear regression Analysis was performed. For all tests meaningfulness was accepted when p<0.05. Results: At the initial moment of the study, it wasn´t observed statistically significant difference in relation to the analyzed variables, between COC1 and COC2 and control groups, except for the percentage of body fat, when the adolescents of the COC2 group differed from the controls and the COC1 group. By the analysis of Simple Linear Regression it was evidenced that, in order to study the effect of all indicators on the basis of age, in the control group for each additional year of chronological age, there was an increase in the bone age of 1.04 years, 3.42 kg of body weight, 1.33 kg/m² of BMI and, 0.1 m in height. Regarding to the densitometric variables analyzed, significant staticall differences were found in lumbar spine BMD, total and subtotal body, with an increase of 0.06 g /cm² in each additional year. There were increases in lumbar spine BMD, total and subtotal body, of 3.22 g, 117.21 g and 89.36g respectively, with significant differences, p < 0.001. As regards to fat mass and lean mass, there was also an increase. Concerning to markers of bone formation (FAO,OC) there was a reduction in the FAO concentration of 5.48 U/L, statistically significant. There was no significant difference in relation to OC. When the medians of the variable anthropometrics, bone densitometrics of body corporal composition and the concentrations of the bone markers FAO and OC obtained at baseline were compared to those obtained after 12 months, among adolescents exposed at the two COC formulations, it was observed that there was statistical difference regarding to chronological age and bone age. As for the other variables analyzed, there were significant differences between the anthropometric variables weight and BMI, in both groups and, in stature for the COC2 group and no differences were observed for the BMI percentile and BMI z score. Regarding to the variables obtained by the DXA in several analyzed sites in comparison of baseline and one year, among the users of COCs, there were no significant differences for BMD and Lumbar BMC, BMD and BMC total body and BMD and BMC subtotal for the group COC2 and of all the same variables, except for the total body BMC for the COC1 group, p= 0.001. In regard to the concentrations of bone formation biomarkers (FAO,OC), there was a reduction, in the medians of the FAO in baseline compared to one year of use in COC1 and COC2, with a significant difference, p=0.040 and p < 0.001. Reductions in osteocalcin concentrations could also be observed 12 months later, in the COC1 group, p= 0.002, and in COC2, p < 0.001. Conclusion: The use of two formulations of low-dose oral hormonal contraceptives, after one year of follow-up is associated to negative effects on bone mass, with increases in density and bone mineral content short of that evidenced for this age group and with a significant reduction in the concentrations of bone markers of formation (FAO and OC), when the results compared to those coming from control adolescents non users of contraceptives.
Abstract. Objective: The objective of this study was to evaluate prospectively the repercussions on bone metabolism of incomplete adolescents from 12 to 20 years old, using oral low-dose hormonal contraceptive (COC), containing EE 20 μg/Desogestrel 150 μg or EE 30 μg Drospirenone 3 mg, for one year period, comparing the results to those obtained among healthy adolescents who did not use COC. Case study and methods: This was a quasi-experimental study The enclosed adolescents were divided into three groups: COC1 group (EE 20 μg Desogestrel 150 μg) compounded of 42 adolescents, COC2 group (EE 30 μg Drospirenone 3 mg) with 66 participants and 70 who composed the control group. All the adolescents at the moment of the inclusion were submitted to the anthropometric, densitrometric (DXA) evaluation, obtaining bone mineral density (BMD) and bone mineral content(BMC) of lumbar spine, total and subtotal body lean mass, fat mass and % fat, performed XR bone age. They were invited to the blood collection, obtaining markers of bone formation, osteocalcin (OC) and bone alkaline phosphatase. After 12 months of COCs use, the adolescents were submitted to a new similar evaluation to that one of the initial moment and request of β Estradiol dosage, after six months of contraceptive use. For the comparison between the variables of the non-users and users of COC1 and COC2 at baseline, the Krus Kal Wallis test was used and, for the comparison between the groups COC1 and COC2 at baseline, Mann-Whitney test was used. Either at baseline or in the comparison baseline, and 12 months of use of the COCs, the Wilcoxom test, set the level of significance at 5%. To study the effect of age on the nutritional variables, densitometric measurements and on the concentrations of bone markers in non-users adolescents of contraceptives (controls),Linear regression Analysis was performed. For all tests meaningfulness was accepted when p<0.05. Results: At the initial moment of the study, it wasn´t observed statistically significant difference in relation to the analyzed variables, between COC1 and COC2 and control groups, except for the percentage of body fat, when the adolescents of the COC2 group differed from the controls and the COC1 group. By the analysis of Simple Linear Regression it was evidenced that, in order to study the effect of all indicators on the basis of age, in the control group for each additional year of chronological age, there was an increase in the bone age of 1.04 years, 3.42 kg of body weight, 1.33 kg/m² of BMI and, 0.1 m in height. Regarding to the densitometric variables analyzed, significant staticall differences were found in lumbar spine BMD, total and subtotal body, with an increase of 0.06 g /cm² in each additional year. There were increases in lumbar spine BMD, total and subtotal body, of 3.22 g, 117.21 g and 89.36g respectively, with significant differences, p < 0.001. As regards to fat mass and lean mass, there was also an increase. Concerning to markers of bone formation (FAO,OC) there was a reduction in the FAO concentration of 5.48 U/L, statistically significant. There was no significant difference in relation to OC. When the medians of the variable anthropometrics, bone densitometrics of body corporal composition and the concentrations of the bone markers FAO and OC obtained at baseline were compared to those obtained after 12 months, among adolescents exposed at the two COC formulations, it was observed that there was statistical difference regarding to chronological age and bone age. As for the other variables analyzed, there were significant differences between the anthropometric variables weight and BMI, in both groups and, in stature for the COC2 group and no differences were observed for the BMI percentile and BMI z score. Regarding to the variables obtained by the DXA in several analyzed sites in comparison of baseline and one year, among the users of COCs, there were no significant differences for BMD and Lumbar BMC, BMD and BMC total body and BMD and BMC subtotal for the group COC2 and of all the same variables, except for the total body BMC for the COC1 group, p= 0.001. In regard to the concentrations of bone formation biomarkers (FAO,OC), there was a reduction, in the medians of the FAO in baseline compared to one year of use in COC1 and COC2, with a significant difference, p=0.040 and p < 0.001. Reductions in osteocalcin concentrations could also be observed 12 months later, in the COC1 group, p= 0.002, and in COC2, p < 0.001. Conclusion: The use of two formulations of low-dose oral hormonal contraceptives, after one year of follow-up is associated to negative effects on bone mass, with increases in density and bone mineral content short of that evidenced for this age group and with a significant reduction in the concentrations of bone markers of formation (FAO and OC), when the results compared to those coming from control adolescents non users of contraceptives.
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Palavras-chave
adolescentes, anticoncepcionais orais, densidade óssea, osteocalcina, remodelação óssea, adolescents, oral contraceptives, bone density, osteocalcin, bone remodeling