Papel do Fator de Crescimento de Fibroblasto 21 no metabolismo ósseo e adiposidade medular de pacientes renais crônicos em tratamento conservador
Data
2022-09-30
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Investigar a relação entre o FGF21 sérico e a adiposidade medular com
parâmetros laboratoriais e histomorfométricos ósseos em pacientes com DRC não
dialíticos. Métodos: Esta é uma análise post hoc de dois estudos transversais. O
estudo A incluiu 89 pacientes com DRC estágio 2-5 ND para avaliar os fatores
associados aos níveis de FGF21. O estudo B incluiu 37 pacientes submetidos à
biópsia óssea para avaliação histomorfométrica dos adipócitos da medula. Os níveis
séricos de FGF21, esclerostina e osteocalcina descarboxilada foram quantificados
por ELISA. Foram realizadas análises histomorfométricas do tecido ósseo e medular.
A histomorfometria óssea foi categorizada de acordo com o sistema TMV
(remodelação, mineralização, volume). Resultados: Os níveis de FGF21
aumentaram entre os estágios da DRC e foram independentemente associados com
a taxa de filtração glomerular estimada, triglicérides, fosfatase alcalina total e
tratamento com estatinas (estudo A). Nos pacientes do estudo B, os níveis de
FGF21 se correlacionaram diretamente com os níveis de osteoprotegerina (OPG) e
com o intervalo de tempo para mineralização e, inversamente, com a taxa de
formação óssea. Quanto à adiposidade medular, o FGF21 se relacionou diretamente
com área e espessura dos adipócitos. A adiposidade medular esteve
independentemente associada com idade, esclerostina e OPG. A área e o número
de adipócitos estiveram associados com volume e microarquitetura óssea.
Considerando-se a classificação TMV, a área adiposa foi maior em pacientes com
baixa remodelação óssea e o número de adipócitos foi maior naqueles com volume
trabecular ósseo diminuído. Conclusão: Em pacientes com DRC não dialíticos, os
níveis séricos do FGF21 foram associados à função renal e alterações lipídicas
(estudo A). No estudo B, o FGF21 se associou a alterações da homeostase óssea e
à adiposidade medular. Por sua vez, a gordura medular se associou à
microarquitetura óssea, à baixa remodelação e volume ósseos e a marcadores
séricos ósseos.
Aim: To investigate the relationship between serum FGF21 and marrow adiposity with laboratory and bone histomorphometric parameters in non-dialysis CKD patients. Methods: This was a post hoc analysis of two cross-sectional studies. The study A included 89 CKD patients stage 2-5ND to evaluate the factors associated with FGF21 levels. The study B included 37 patients who underwent transiliac bone biopsy for histomorphometric assessment of marrow adipocytes. Serum levels of FGF21, sclerostin and undercarboxylated osteocalcin were quantified by ELISA. Histomorphometric analysis of bone and marrow tissues was performed. Bone histomorphometry was categorized according to the TMV System. Results: FGF21 levels increased among CKD stages and were independently associated with estimated glomerular filtration rate, triglycerides, total alkaline phosphatase and statins therapy (study A). In study B patients, FGF21 levels correlated directly with osteoprotegerin levels (OPG) and mineralization lag time and inversely with bone formation rate. On marrow adiposity, FGF21 was directly related to adipocyte width and area. Marrow adiposity was independently associated with age, sclerostin and OPG. Adipocyte area and number were associated with bone volume and microarchitecture. Regarding the TMV classification, the adipose area was greater in patients with low bone turnover and the adipocyte number was higher in those with decreased trabecular bone volume. Conclusion: In non-dialyzed CKD patients, serum FGF21 levels were associated with renal function and lipid alterations (study A). In the study B, FGF21 was correlated with abnormal bone homeostasis and marrow adiposity. In its turn, marrow adiposity was associated with bone microarchitecture, low bone turnover and volume, and serum bone markers.
Aim: To investigate the relationship between serum FGF21 and marrow adiposity with laboratory and bone histomorphometric parameters in non-dialysis CKD patients. Methods: This was a post hoc analysis of two cross-sectional studies. The study A included 89 CKD patients stage 2-5ND to evaluate the factors associated with FGF21 levels. The study B included 37 patients who underwent transiliac bone biopsy for histomorphometric assessment of marrow adipocytes. Serum levels of FGF21, sclerostin and undercarboxylated osteocalcin were quantified by ELISA. Histomorphometric analysis of bone and marrow tissues was performed. Bone histomorphometry was categorized according to the TMV System. Results: FGF21 levels increased among CKD stages and were independently associated with estimated glomerular filtration rate, triglycerides, total alkaline phosphatase and statins therapy (study A). In study B patients, FGF21 levels correlated directly with osteoprotegerin levels (OPG) and mineralization lag time and inversely with bone formation rate. On marrow adiposity, FGF21 was directly related to adipocyte width and area. Marrow adiposity was independently associated with age, sclerostin and OPG. Adipocyte area and number were associated with bone volume and microarchitecture. Regarding the TMV classification, the adipose area was greater in patients with low bone turnover and the adipocyte number was higher in those with decreased trabecular bone volume. Conclusion: In non-dialyzed CKD patients, serum FGF21 levels were associated with renal function and lipid alterations (study A). In the study B, FGF21 was correlated with abnormal bone homeostasis and marrow adiposity. In its turn, marrow adiposity was associated with bone microarchitecture, low bone turnover and volume, and serum bone markers.