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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 4  |  Page : 1867-1871

Bone mineral density in patients with juvenile idiopathic arthritis and its relation to disease activity


1 Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Rheumatology and Rehabilitation, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission06-Oct-2022
Date of Decision23-Oct-2022
Date of Acceptance24-Oct-2022
Date of Web Publication04-Mar-2023

Correspondence Address:
Dalia A Nofal
Department of Physical Medicine, Rheumatology and Rehabilitation, Menoufia University, Tala, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_339_22

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  Abstract 


Objectives
To measure bone mineral density (BMD) in patients with juvenile idiopathic arthritis (JIA) and to relate it to disease activity.
Background
Low BMD is a common finding in children with JIA. It is associated with a high risk of osteopenia and osteoporosis, which increases the risk of fracture. Dual-energy radiograph absorptiometry (DEXA) of the lumbar spine using the Z score is used for measurement of BMD in pediatrics.
Patients and methods
The study included 50 patients diagnosed and assessed clinically as JIA (20 females and 30 males). The patients were diagnosed as having JIA according to the criteria of classification of the International League of Associations for Rheumatology. BMD was measured in the lumbar spine using the Z score. The results were correlated with juvenile arthritis disease duration, disease activity, and serum level of bone turnover markers, vitamin D3, parathyroid hormone, calcium, phosphorus, and magnesium. Clinical disease activity was evaluated by juvenile arthritis disease activity score 27.
Results
The study showed that 36% of patients had low BMD (Z score of <−2) by DEXA of lumbar spine, 64% of patients had normal BMD (Z score >−2), and no patient was given a diagnosis of osteoporosis (BMD Z score ≤−2 and a significant fracture history). There was a significant negative correlation between BMD (DEXA Z score) and juvenile arthritis disease activity score 27, bone turnover markers, and duration of JIA.
Conclusion
Osteoporosis and osteopenia are common in patients with JIA. BMD decreases among patients with JIA with high disease activity.

Keywords: dual-energy radiograph absorptiometry, juvenile idiopathic arthritis, osteoporosis


How to cite this article:
Soliman SG, Labeeb AA, El Zaiat RS, Nofal DA, Fotoh DS. Bone mineral density in patients with juvenile idiopathic arthritis and its relation to disease activity. Menoufia Med J 2022;35:1867-71

How to cite this URL:
Soliman SG, Labeeb AA, El Zaiat RS, Nofal DA, Fotoh DS. Bone mineral density in patients with juvenile idiopathic arthritis and its relation to disease activity. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1867-71. Available from: http://www.mmj.eg.net/text.asp?2022/35/4/1867/371033




  Introduction Top


Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory diseases that occur in one or more joints, with arthritis lasting at least 6 weeks in children and adolescents under the age of 16 years [1].

There are several extra-articular manifestations related to JIA, each of which has a negative effect on bone health. JIA is a representative disease that adversely affects bone mineral density (BMD) during childhood and adolescence, when peak bone mass is attained [2].

In patients with JIA, as happens in other children with chronic diseases, bone formation may be inhibited by direct and indirect mechanisms [3].

Many factors are associated with decreased BMD in patients with JIA such as low physical activity, reduced joint motility [4], delayed pubertal maturation, malnutrition, early onset of JIA, and its treatments [5].

Decreased BMD is associated with an increased risk of osteopenia and osteoporosis, which increases the risk of fracture [6].

Osteoporosis arises when the amount of bone resorbed exceeds the amount of newly formed bone, resulting in a net loss of bone mass, according to the WHO [7].

Dual-energy radiograph absorptiometry (DEXA) of the lumbar spine is the gold standard for the measurement of BMD in the pediatric age group, as recommended by the International Society for Clinical Densitometry (ISCD) in 2007 [8].

The assessment of BMD through this technique uses the Z score, which expresses the number of SDs that the patient's BMD deviates from the mean BMD of healthy controls of the same age and sex [9]. The aim of this study was to assess BMD in patients with JIA and to relate it to disease activity.


  Patients and methods Top


An observational cross-sectional study included 50 patients diagnosed and assessed clinically as JIA. They were randomly recruited from Physical Medicine, Rheumatology and Rehabilitation Outpatient Clinic, at Menoufia University Hospitals, during the years 2019–2021. The selection of patients was based on the criteria of classification of the International League of Associations for Rheumatology [10].

The study was approved by the Ethical Research Committee and Institutional Review Board of the Faculty of Medicine, Menoufia University, Egypt (approval number: 19519INTPH 48). An informed written consent was obtained from every patient or from their parents before his or her enrollment in the trial.

The present study included patients who were diagnosed as having JIA according to the criteria of classification of the International League of Associations for Rheumatology [10], with disease duration of more than 1 year, all patients were under medical treatment of JIA, and patients' ages ranged from 5 to 16 years old. Patients with history of receiving corticosteroids, patients who received other drugs not prescribed for JIA and cause affection of BMD, patients who had any other autoimmune diseases, patients with history of other chronic diseases causing osteoporosis (e.g. endocrinal, hematologic, and renal diseases), and patients with neurological disorders (e.g. cerebral palsy and spasticity) were excluded from the current study.

All patients were subjected to the following: demographic data recording, history taking, and clinical examination (general examination [11] and local examination of joints [12]). Laboratory investigations included complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein titer, albumin/creatinine ratio, serum calcium (total and ionized), phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D3, and bone turnover markers (serum osteocalcin for bone formation and C terminal telopeptide of type 1 collagen for bone resorption).

Radiological investigations included DEXA scan on lumbar spine using Z score to assess BMD. The Z score is a comparison of person's BMD with that of an average person of the same age and sex. The T score, which is used in adult interpretation of DEXA, should not be included in the pediatric DEXA report because T score reflects comparison to peak BMD in adults, and its use in children who have not yet reached peak BMD would be meaningless and may result in an inaccurate diagnosis of low BMD and/or unnecessary medical intervention. In this study, we used the lunar DPX DEXA System (analysis version 14.10) (General Electric Healthcare, Waukesha, Wisconsin, USA). Radiography (radiograph on lumbar spine) was used to detect vertebral fractures. Conventional radiographs remain the gold standard imaging modality for diagnosing vertebral fractures in children, mainly owing to convenience and availability. FRAX score quantify the 10-year probability of hip or major osteoporotic fractures but not detect the presence of old fractures.

Assessment of disease activity using the juvenile arthritis disease activity score (JADAS-27) [13], which includes four items: physician global assessment of disease activity measured on a 0–10 visual analog scale (VAS), where 0 = no activity and 10 = maximum activity; parent/patient global assessment measured on a 0–10 VAS, where 0 = very well and 10 = very poor; number of active joints; and ESR normalized to a 0–10 scale.

JADAS = active joint count + physician global + parent global (10 cm VAS)+ESR [13].

Statistical analysis

Data were collected, tabulated, and statistically analyzed using an IBM compatible personal computer with the Statistical Package for the Social Sciences (SPSS), version 23 (SPSS Inc. Released 2015. IBM SPSS statistics for Windows, version 23.0; IBM Corp., Armonk, New York, USA) [14]. Descriptive statistics included the following: qualitative data were expressed as number and percentage, whereas quantitative data were expressed as mean, SD, and range (minimum–maximum). Analytic statistics included the following: Mann–Whitney U test was used for comparison of quantitative variables between two groups of not normally distributed data [15], Kruskal–Wallis test was used for comparison of quantitative variables between more than two groups of not normally distributed data, and Spearman correlation was used to show correlation between two continuous not normally distributed variables [16]. Significant test results were quoted as two-tailed probabilities. Significance of the obtained results was judged at the 5% level (P > 0.05).


  Results Top


This study included 50 patients (30 males and 20 females). The mean age was 12.81 ± 3.15 years, ranging from 6 to 16 years. The mean disease duration was 3.63 ± 2.11 years.

Regarding JIA types, this study showed that 26% of patients had polyarticular with rheumatoid factor positive, 22% of patients had oligoarticular JIA, 20% of patients had systemic JIA, 16% of patients had polyarticular JIA with rheumatoid factor negative, and 16% of patients had enthesitis-related JIA [Table 1].
Table 1: Clinical parameters of the patients (n=50)

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This study showed that 18 (36%) patients had osteopenia (Z score ≤2) and 32 (64%) patients had normal BMD (Z score >−2) by DEXA of lumbar spine. On the contrary, no patient was given a diagnosis of osteoporosis (BMD Z score ≤−2 and a significant fracture history), and radiograph of lumbar spine was normal in 100% of the patients [Table 2].
Table 2: Radiological parameters in the patients (n=50)

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There were highly significant differences between types of JIA and DEXA Z score. DEXA Z score is lower in enthesitis-related type and polyarticular RF positive type than other types, with mean of −2.53 ± 1.07 in enthesitis-related arthritis and −2.60 ± 0.12 in the polyarticular RF positive type. Mean Z score in other types of JIA was −1.60 ± 0.09 in polyarticular RF negative type, −1.36 ± 0.05 in systemic onset type, and −1.51 ± 0.09 in oligoarticular type. There were significant low vitamin D3 levels among patients with low DEXA score (P = 0. 049) [Table 3].
Table 3: Comparison between bone mineral density (dual-energy radiograph absorptiometry Z score) versus types of juvenile idiopathic arthritis, and vitamin D3 level

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There were positive correlations between BMD (DEXA Z score) and vitamin D3 level (P = 0.317) and phosphorus level (P = 0.737). Moreover, there were negative correlations between BMD (DEXA Z score) and bone turnover markers (P < 0.001), total calcium level (P = 0.3), ionized calcium level (P = 0.064), magnesium level (P = 0.727), and parathyroid hormone level (P = 0.57) [Table 4].
Table 4: Correlation between bone mineral density (dual-energy radiograph absorptiometry Z score) versus laboratory parameters

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There were significant negative correlations between BMD (DEXA Z score) and duration of JIA (P = 0.006) and disease activity (JADAS-27) (P < 0.001) [Table 5].
Table 5: Correlation between bone mineral density (dual-energy radiograph absorptiometry Z score) versus bone turnover markers and clinical parameters

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  Discussion Top


The aim of our study was to assess BMD in patients with JIA and its relation to disease activity.

We reported that 36% of patients had low BMD (Z score ≤2) by DEXA of lumbar spine. On the contrary, no patient was given a diagnosis of osteoporosis (BMD Z score ≤−2 and a significant fracture history) and radiograph of lumbar spine was normal in 100% of the patients.

In agreement with us, the study by Helmy Shalaby et al.[17] reported that low BMD (BMD Z score ≤−2) was given in 25% of patients by DEXA of lumbar spine, and 20% by DEXA of total body less head without a given a diagnosis of osteoporosis (BMD Z score ≤−2 and a significant fracture history). Moreover, Gattu et al.[18] in another study conducted on 41 children with JIA found a reduced bone density in 36.5% patients with JIA.

On the contrary, Zavala et al.[9] in their cross-sectional study on Spanish patients with JIA documented low prevalence of osteopenia (<5%). We can explain the difference in their results from ours by the different nutritional habits of Egyptian population, regarding low physical activity and low sun exposure.

In our study, there was a highly significant difference between types of JIA and DEXA Z score. DEXA Z score is lower in enthesitis-related type and polyarticular RF positive type than other types. This is explained by the low physical activity of those groups of patients.

In agreement of our result, the study by Kuntze et al.[19] reported that Z scores were significantly lower in patients with polyarticular JIA and those with spondyloarthropathy.

On the contrary, the study by El Badri et al.[20] reported that BMD regarding Z score in lumbar spine showed a statistically significant correlation between BMD and systemic subtype of JIA. Moreover, in the study by Shin et al. [4], patients with systemic JIA had lower BMD values. In addition, Hassan et al.[21] concluded that children with JIA who have oligoarticular and systemic onset of JIA patients were more susceptible to low BMD. These differences in our results may be explained by the small number of patients.

In our study, vitamin D3 level was significantly low in case of low DEXA Z score.

Moreover, the study by El Badri et al.[20] reported that 75% of the patients with vitamin D deficiency (<10 ng/ml) had a low BMD.

In the present study, there were highly significant negative correlations between BMD (DEXA Z score) and bone turnover markers (P < 0.001).

Moreover, the study by Zavala et al.[9] reported high bone turnover in patients with lower BMD values.

On the contrary, the study by Janicka-Szczepaniak et al.[22] documented that there were no associations between markers of bone turnover and DEXA results. Moreover, Qu et al.[23] found a positive correlation between BMD and osteoprotegerin levels in patients with JIA. These differences from our results may be explained by a high biological and circadian variability of bone turnover markers.

In our study, there was a significant negative correlation between BMD (DEXA Z score) and duration of JIA, and this may be explained by increased chance for accumulation of inflammatory markers in long disease duration, and also long periods of immobility and decreased physical activity can cause decreased bone formation.

This is in concordance with Hassan et al. [21], who concluded that patients with longer duration of JIA at diagnosis had more osteopenia and osteoporosis than those with short duration of disease. In addition, Islam et al.[24] reported that the disease duration had a positive relationship with lower BMD in patients with JIA.

Our study showed a significant negative correlation between BMD (DEXA Z score) and JADAS.

This is in concordance with the study by Dey et al. [25], who reported that BMD had a negative correlation with disease activity measures (active joint count, JADA score, ESR, and C-reactive protein). Moreover, the study by Sumi et al.[26] concluded that there was an association between decreased bone mineralization in JIA and disease severity.

In addition, the study by Helmy Shalaby et al.[17] reported that BMD was significantly lower in patients with high disease activity. Moreover, the study by Janicka-Szczepaniak et al.[22] recommended performing DEXA measurements every 6 months in patients with higher disease activity.

In contrast to this study, the results of Bettaieb et al.[27] showed that neither osteoporosis (P = 0.37) nor osteopenia (P = 0.25) was associated with disease activity score. They concluded that long-term corticosteroid therapy and sedentary lifestyle seem to be correlated with more impaired bone abnormalities.


  Conclusion Top


Osteopenia is a frequent complication of JIA. Patients with higher disease activity are at a higher risk of osteopenia, as high disease activity affects the level of vitamin D in the blood negatively and, in turn, decreases BMD. Well-timed, efficient treatment, and proper control of JIA disease activity may help to improve bone status and reduce incidence of osteoporosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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