Impact of Somatic Development and Course of Osteogenesis Imperfecta on FGF23 Levels in Children

成骨不全症的体格发育和病程对儿童FGF23水平的影响

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Abstract

Osteogenesis imperfecta (OI) is a rare bone dysplasia that occurs with a frequency of 1/15,000-20,000 live births. It is characterized by increased susceptibility of bone fractures, skeletal deformities, low stature, and low bone mass. It results in impaired production of type I collagen. About 90% of people with OI have heterozygous mutations in the COL1A1 and COL1A2 genes. Fibroblast growth factor 23 (FGF23) is a protein involved in the regulation of phosphate and 1,25-dihydroxyvitamin D(3) metabolism on a negative feedback basis. FGF23 is secreted by osteocytes in response to increased serum calcitriol and phosphorus. The purpose of this study was to evaluate the concentration of FGF23 among children with osteogenesis imperfecta and the differences in reference values in a healthy population of children and adolescents. Then, this study sought to evaluate how the course of osteogenesis imperfecta, including type of disease, number of bone fractures, and bone mineral density, are related to FGF23 concentration. The study included 47 children aged 3 to 17 years with a diagnosis of osteogenesis imperfecta, confirmed by genetic tests. The patients were hospitalized at the Department from August 2019 to September 2020 and were treated with intravenous infusions of sodium pamidronate. The course of the disease was analyzed, including the number of bone fractures, clinical symptoms, and anthropometric parameters, and bone densitometry was performed by dual X-ray absorptiometry (DXA) in Total Body Less Head (TBLH) and Spine options with Z-score evaluation. FGF23 concentration was determined by the ELISA method. The study was prospective in nature. Results: The mean level of FGF23 in the study group of patients was 645.09 pg/mL and was within the reference values for the developmental age population. There was no significant correlation between FGF23 concentration and anthropometric measurements: body weight (p = 0.267), height (p = 0.429), gender (p = 0.291), or pubertal stage (p = 0.223) in the study group of patients. FGF23 levels were not related to the number of fractures (p = 0.749), the number of sodium pamidronate cycles administered (p = 0.580), bone mineral density parameters (Z-score), the form of osteogenesis imperfecta (p = 0.156), or the genetic test result (p = 0.573). FGF23 levels decrease with age (r = -0.32, p = 0.030) and BMI (r = -0.34, p = 0.020). The level of FGF23 in patients with osteogenesis imperfecta is lower among older children and those having a higher BMI. This index cannot be a diagnostic tool in this group of patients, for no differences were found between the concentrations in patients with osteogenesis imperfecta and the developmental age population.

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