The dissertation focuses on enhancing the effectiveness of diagnosing osteopenic syndrome (OS) in children with juvenile idiopathic arthritis (JIA) by identifying early, informative prognostic predictors of its development based on the analysis of clinical, laboratory and functional parameters of the underlying disease course..
To achieve the set objective, the study was conducted in three stages. The first stage involved a retrospective analysis of medical records for all children, evaluating the age of JIA onset, disease duration, clinical features of the disease and treatment modalities. The second stage included an analysis of laboratory-instrumental study results (including ultrasound densitometry and determination of BMM in serum) for patients, who were subsequently divided into two subgroups based on bone mineral density: children with osteopenic syndrome (OS) (n=61) and without OS (n=86). The third stage encompassed a mathematical-statistical analysis to determine the informativeness and specificity of individual parameters, followed by the development of a prognostic model for the risk of osteopenia development in children with JIA.
The results of laboratory investigations revealed that interleukin-6 levels in children with OS were significantly higher compared to those without OS (17.4 [10.7; 23.4] vs. 10.2 [6.8; 14.8] pg/mL; p<0.05).
The assessment of serum 25(OH)D levels, a key diagnostic criterion for OS, demonstrated that in children with OS, these levels were significantly lower than in those without OS, measuring 17.3 [14.3; 25.8] vs. 28.8 [20.6; 46.3] ng/mL (p<0.05). No significant differences were observed in the mean levels of ionized calcium or phosphorus in the serum of children with and without OS. The conducted ROC analysis enabled the determination of an optimal threshold value for serum 25(OH)D content for predicting OS in children with JIA at 27.5 ng/mL.
The study determined that the level of ostease, the bone-specific isoenzyme of alkaline phosphatase, in the serum of children with OS was significantly higher than in those without OS (115.5 [95.8; 127.6] vs. 43.6 [30.2; 65.4] µg/mL; p<0.05) and correlated with 25(OH)D levels (r=-0.48, p<0.05), osteocalcin (r=-0.36, p<0.05), β-CrossLaps (r=0.63, p<0.05), Z-scores from ultrasound densitometry (r=-0.51, p<0.05), disease activity (r=0.34, p<0.05), and methotrexate dosage in baseline therapy (r=0.30, p<0.05). These findings indicate the specificity of this biomarker. Meanwhile, the level of total alkaline phosphatase (ALP) in the serum of children with JIA remained within age-specific reference ranges and did not differ significantly between subgroups. No correlation was found between total ALP levels and its bone-specific isoenzyme (ostease), 25(OH)D levels, Z-scores of ultrasound densitometry. Thus, total ALP in children with JIA is a nonspecific indicator, as its normal activity in serum does not exclude alterations in the bone isoenzyme pattern.
For the first time, based on the obtained clinical-laboratory data, prognostic scales were developed and proposed. These scales can be used in clinical pediatrics for personalized assessment of the risk degree of OS development in children with JIA, identification of high-risk groups, and implementation of preventive measures for potential complications.
Thus, this study supports the concept that the primary factor influencing the development and severity of osteopenia in JIA is the activity of the inflammatory process. This is demonstrated by the established associations between reduced bone density, clinical disease activity, serum levels of interleukin-6, and vitamin D. The processes of impaired osteogenesis begin with the activation of bone resorption among systemic inflammation in children with JIA, even before overt clinical-instrumental manifestations of osteopenia. The determination of serum BMM in such patients expands the opportunities for early-stage diagnosis of osteopenia.
