Luuston terveys, kehon koostumus ja adipokiinit lastenreumassa

Children with juvenile idiopathic arthritis (JIA) are predisposed to compromised bone health and alterations in body composition because of chronic inflammation, nutritional and hormonal disturbances, limited physical activity and glucocorticoid (GC) therapy. Compromised bone health may present as pathological vertebral compression fractures, but data on their prevalence and risk factors in children are limited. Excess fat, and especially adipose tissue-derived adipokines leptin and adiponectin, may also contribute to impaired bone health. Furthermore, adipokines modulate immunity and inflammation in adults with rheumatic diseases, but their role in JIA has not been explored. We evaluated bone health in patients with severe JIA and investigated body composition and adipokines and their contribution to bone health and disease activity in JIA. We recruited two cohorts of patients for cross-sectional studies. The Severe JIA Cohort comprised 50 patients with severe polyarticular or systemic JIA. The GC-treated Cohort included 50 patients with JIA with mostly mild to moderate disease severity and at least three months' exposure to systemic GC. The results were compared with those of sex-and age-matched healthy controls. The study protocol included clinical and laboratory assessments, evaluation of bone mineral density (BMD) and body composition by dual-energy X-ray absorptiometry (DXA), spinal radiography and spinal magnetic resonance imaging (MRI). Spinal radiography showed vertebral compression fractures in 22% of the patients with severe JIA. Patients with fractures had higher weight-adjusted cumulative GC dose, higher disease activity and higher body mass index than those without fractures. Bone age-corrected BMD Z-scores for lumbar spine and whole body were similar between those with and without fractures. On spinal MRI, altogether 28% of patients with severe JIA showed vertebral fractures and several other vertebral changes, including end plate irregularities in 26%, anterior vertebral corner lesions in 16% and disc changes in 46%. Based on concentrations of bone turnover markers, the patients with severe JIA had increased bone resorption, but normal bone formation. Further, patients with severe JIA had increased body adiposity, and their serum leptin was increased even independently of fat mass. Leptin showed an inverse association with bone turnover markers in patients, while in controls the association was dependent on fat mass. In the GC-treated Cohort, fat mass, lean mass and serum leptin and adiponectin were similar to those of controls, but patients had slightly lower BMD values than controls. Those patients with lumbar spine BMD Z-score -1.0 tended to have higher serum leptin values than those with higher BMD Z-scores, but in regression analysis leptin was not associated with BMD. Adipokines did not correlate with current disease activity in either patient cohort. Patients with severe JIA have compromised bone health based on high prevalence of compression fractures. Risk factors include high GC exposure, high disease activity and high body mass index. BMD, as measured by DXA, is unable to differentiate between those with and without compression fractures. According to spinal MRI findings, patients with severe JIA have, besides compression fractures, several other changes involving intervertebral discs and vertebral end plates; the clinical relevance of these remains uncertain. Patients with severe JIA are prone to high adiposity, whereas those with less severe disease have normal body composition despite previous GC exposure. Leptin may negatively contribute to bone metabolism in severe JIA, but larger and longitudinal studies are needed to prove causality and to evaluate whether these preliminary findings are generalizable to other JIA groups. We did not observe a correlation between leptin or adiponectin and disease activity in either JIA cohort. The possible role of adipokines as a modulator of immunity and inflammation in JIA remains to be evaluated.Lastenreumaan eli juveniiliin idiopaattiseen artriittiin (JIA) voi liittyä kehon koostumuksen muutoksia ja luuston haurastumista. Altistavia tekijöitä ovat krooninen tulehdustila, ravitsemukselliset ja hormonaaliset tekijät, luustoa kuormittavan liikunnan vähäisyys sekä glukokortikoidihoito. Kroonisesti sairailla lapsilla voi esiintyä selkänikamien murtumia viitaten patologiseen luuston haurauteen. Nikamamurtumien esiintyvyydestä, riskitekijöistä ja diagnostiikasta lastenreumassa on rajallisesti tutkittua tietoa. Myös lihavuus saattaa vaikuttaa haitallisesti luustoon. Rasvakudoksen ja luuston välisen vuorovaikutuksen mekanismeja tunnetaan vielä melko huonosti, mutta leptiinin ja adiponektiinin on esitetty olevan osallisina. Nämä ns adipokiinit myös muokkaavat immuunivastetta. Lastenreumaa sairastavilla leptiinin ja adiponektiinin yhteyttä taudin aktiivisuuteen ei ole tutkittu. Tutkimuksen tarkoituksena oli selvittää nikamamurtumien ja muiden selkärangan poikkeavuuksien esiintyvyyttä ja riskitekijöitä vaikeaa lastenreumaa sairastavilla potilailla. Lisäksi tutkittiin lastenreumaa sairastavien lasten ja nuorten kehon koostumusta, adipokiinien pitoisuuksia ja adipokiinien yhteyttä luuston aineenvaihduntaan, luun mineraalitiheyteen ja taudin aktiivisuuteen. Poikkileikkaustutkimukseen rekrytoitiin kaksi potilaskohorttia. Toisessa kohortissa oli 50 vaikeaa lastenreumaa sairastavaa lasta ja nuorta. Toisessa kohortissa oli 50 lastenreumapotilasta, jotka olivat saaneet systeemistä glukokortikoidihoitoa vähintään 3 kuukauden ajan, mutta joiden lastenreuma oli luonteeltaan keskimäärin lievempi. Adipokiinien, luustomarkkereiden ja luun mineraalitiheyden välistä vuorovaikutusta selvittäneissä tutkimuksissa tuloksia verrattiin iän ja sukupuolen suhteen kaltaistettujen terveiden verrokeiden tuloksiin. Tutkittaville tehtiin kliininen tutkimus, laboratoriotutkimuksia ja luuston mineraalitiheyden mittaus. Vaikeaa lastenreumaa sairastaville potilaille tehtiin lisäksi selkärangan röntgenkuvaus ja magneettikuvaus. Tulokset osoittivat, että selän nikamamurtumat ja muut poikkeavuudet ovat yleisiä vaikeaa lastenreumaa sairastavilla. Heistä 22%:lla todettiin nikamamurtumia selän röntgenkuvissa. Kolmen edeltävän vuoden kumulatiivinen painoon suhteutettu kortisoniannos, taudin aktiivisuus ja painoindeksi olivat suuremmat nikamamurtumia saaneilla verrattuna niihin, joilla murtumia ei todettu. Luuston mineraalitiheys ei kuitenkaan eronnut näiden ryhmien välillä. Selkärangan magneettikuvauksessa nikamamurtumia oli 28%:lla ja lisäksi havaittiin runsaasti muita muutoksia: päätelevyn epätasaisuuksia (26%), nikaman etunurkan muutoksia (16%) sekä välilevymuutoksia (46%). Niillä joilla kuvantamismuutoksia todettiin, oli taipumus olla muita lihavampia. Vaikeaa lastenreumaa sairastavilla luuston hajoamista kuvaavan merkkiaineen pitoisuus oli korkeampi, mutta muodostusmarkkereiden pitoisuudet eivät eronneet verrokeihin nähden. Vaikeaa lastenreumaa sairastavat olivat selvästi lihavampia kuin verrokit. Heillä todettiin korkeampi seerumin leptiinipitoisuus sekä käänteinen yhteys leptiinin ja luustomarkkereiden välillä myös silloin, kun rasvan määrä sekoittavana tekijänä otettiin huomioon. Verrokeilla vastaava yhteys näytti olevan rasvakudoksesta riippuvainen. Glukokortikoidihoitoa saaneiden mutta lievempää lastenreumaa sairastavien lasten kohortissa kehon koostumus tai seerumin leptiini- ja adiponektiinipitoisuudet eivät eronneet verrokeista. Potilailla oli kuitenkin lievästi alentunut luun mineraalitiheys. Potilailla, joilla lannerangan luuntiheys oli ≤-1.0 SD, oli taipumus suurempaan leptiinipitoisuuteen kuin niillä joiden luuntiheys oli >-1.0 SD. Leptiini ei kuitenkaan ollut yhteydessä luun mineraalitiheyteen monimuuttuja-analyysissä. Leptiini ja adiponektiini eivät korreloineet taudin aktiivisuuteen kummassakaan lastenreumaa sairastavien kohortissa. Nikamamurtumat ovat yleisiä vaikeaa lastenreumaa sairastavilla lapsilla ja nuorilla. Altistavia tekijöitä ovat korkea kolmen edeltävän vuoden kumulatiivinen kortisoniannos, taudin aktiivisuus ja lihavuus. Luuston mineraalitiheysmittaus ei kykene erottelemaan nikamamurtumia saaneita muista potilaista. Selkärangan magneettikuvaus löytää enemmän murtumia, mutta myös runsaasti muita muutoksia. Vaikea lastenreuma altistaa lihavuudelle, mutta lievempää tautia sairastavien kehon koostumus ei eroa terveistä ikätovereista. Altistuminen pieniannoksiselle kortisonihoidolle ei näytä vaikuttavan haitallisesti kehon koostumukseen. Leptiinillä saattaa olla negatiivinen vaikutus luuston aineenvaihduntaan vaikeassa lastenreumassa. Tutkimuksessa ei todettu yhteyttä leptiinin tai adiponektiinin ja taudin aktiivisuuden välillä

Impaired cardiorespiratory and neuromuscular fitness in children and adolescents with juvenile idiopathic arthritis : a cross-sectional case–control study in the era of biologic drug therapies

Background: In recent years, biologic drug therapies have altered the course of juvenile idiopathic arthritis (JIA) possibly also improving the patients’ physical fitness. However, studies measuring both cardiorespiratory and muscular fitness in children with JIA are sparse and have failed to show consistent results. Our aim was to assess both cardiorespiratory and neuromuscular fitness and contributing factors in children and adolescents with JIA in the era of biologic drug therapies. Methods: This cross-sectional study consisted of 73 JIA patients (25 boys, 48 girls) aged 6.8- 17.5 years and 73 healthy age- and sex-matched controls, investigated in 2017–2019. Cardiorespiratory fitness was assessed by maximal ergospirometry and neuromuscular fitness by speed, agility, balance, and muscle strength tests. Results: Means (± SD) of maximal workload (Wmax/kg) and peak oxygen uptake (VO2peak/kg,) were lower in JIA patients than in controls (Wmax/kg: 2.80 ± 0.54 vs. 3.14 ± 0.50 Watts, p < 0.01; VO2peak/kg: 38.7 ± 7.53 vs. 45.8 ± 6.59 ml/min/kg, p < 0.01). Shuttle-run, sit-up and standing long jump test results were lower in JIA patients than in controls (p < 0.01). Mean (± SD) daily activity was lower (89.0 ± 44.7 vs. 112.7 ± 62.1 min/day, p < 0.05), and sedentary time was higher (427 ± 213 vs. 343 ± 211 min/day, p < 0.05) in JIA patients compared to controls. Physical activity and cardiorespiratory or neuromuscular fitness were not associated with disease activity. Conclusions: JIA patients were physically less active and had lower cardiorespiratory and neuromuscular fitness than their same aged controls with no JIA. Therefore, JIA patients should be encouraged to engage in physical activities as a part of their multidisciplinary treatment protocols to prevent adverse health risks of low physical activity and fitness.publishedVersionPeer reviewe

Pain-coping scale for children and their parents : a cross-sectional study in children with musculoskeletal pain

BackgroundIn a chronic pain-causing disease such as juvenile idiopathic arthritis, the quality of coping with pain is crucial. Parents have a substantial influence on their children's pain-coping strategies. This study aimed to develop scales for assessing parents' strategies for coping with their children's pain and a shorter improved scale for children usable in clinical practice.MethodsThe number of items in the Finnish version of the pain-coping questionnaire for children was reduced from 39 to 20. A corresponding reduced scale was created for parental use. We recruited consecutive patients from nine hospitals evenly distributed throughout Finland, aged 8-16 years who visited a paediatric rheumatology outpatient clinic and reported musculoskeletal pain during the past week. The patients and parents rated the child's pain on a visual analogue scale from 0 to 100 and completed pain-coping questionnaires and depression inventories. The selection process of pain questionnaire items was performed using factor analyses.ResultsThe average (standard deviation) age of the 130 patients was 13.0 (2.3) years; 91 (70%) were girls. Four factors were retained in the new, improved Pain-Coping Scales for children and parents. Both scales had 15 items with 2-5 items/factor. The goodness-of-fit statistics and Cronbach's alpha reliability coefficients were satisfactory to good in both scaled. The criterion validity was acceptable as the demographic, disease related, and the depression and stress questionnaires correlated with the subscales.ConclusionsWe created a shorter, feasible pain-coping scale for children and a novel scale for caregivers. In clinical work, the pain coping scales may serve as a visualisation of different types of coping strategies for paediatric patients with pain and their parents and facilitate the identification of families in need of psychological support.Peer reviewe

metabolic bone disease and osteoporosis in children

To understand the basics of pediatric bone metabolism and mechanisms underlying osteoporosi

Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis

Abstract Objectives: To evaluate the patterns of usage, efficacy and safety of tocilizumab in polyarticular JIA. Methods: An observational study of 56 consecutive polyarticular JIA patients was conducted using patient charts and electronic JIA databases. Efficacy was assessed by tocilizumab survival, rates of low disease activity (LDA) and of inactive disease by 10-joint Juvenile Arthritis Disease Activity Score (JADAS-10), and of clinically inactive disease according to Wallace’s preliminary criteria. Efficacy and rate of adverse events (AEs) were evaluated during a 24-month period after tocilizumab commencement. Results: Tocilizumab was started on average as third-line biological agent (median, range first- to fourth-line) at a median disease duration of 5.2 years (interquartile range 3.0–7.7). Survival rates were 82% at 12 months and 64% at 24 months. The reasons for discontinuation were inadequate treatment effect in 50%, AE plus inadequate treatment effect in 37.5% and AE alone in 12.5%. LDA (JADAS-10 ⩽3.9) was reached in 58% at 12 months and in 84% at 24 months, inactive disease (JADAS-10 ⩽0.7) in 19% and 44%, and clinically inactive disease in 28% and 46%, respectively. The rate of AEs was 200.9/100 patient years and of serious AEs 12.9/100 patient years. Conclusion: Survival of tocilizumab was high and a large proportion of the treatment-resistant patients reached LDA at 12 months of treatment. The LDA rate continued to increase throughout 24 months. The rates of AEs and serious AEs were higher than in register studies but lower than in the originator study of tocilizumab