Publications by authors named "Solveig Petersen"

38 Publications

Feasibility, reliability and validity of the health-related quality of life instrument Child Health Utility 9D (CHU9D) among school-aged children and adolescents in Sweden.

Health Qual Life Outcomes 2021 Aug 3;19(1):193. Epub 2021 Aug 3.

Department of Epidemiology and Global Health, Umeå University, 901 87, Umeå, Sweden.

Background: This study was conducted in a general population of schoolchildren in Sweden, with the aim to assess the psychometric properties of a generic preference-based health related quality of life (HRQoL) instrument, the Swedish Child Health Utility 9D (CHU9D), among schoolchildren aged 7-15 years, and in subgroups aged 7-9, 10-12 and 13-15 years.

Methods: In total, 486 school aged children, aged 7-15 years, completed a questionnaire including the CHU9D, the Pediatric quality of life inventory 4.0 (PedsQL), KIDSCREEN-10, questions on general health, long-term illness, and sociodemographic characteristics. Psychometric testing was undertaken of feasibility, internal consistency reliability, test-retest reliability, construct validity, factorial validity, concurrent validity, convergent validity and divergent validity.

Results: The CHU9D evidenced very few missing values, minimal ceiling, and no floor effects. The instrument achieved satisfactory internal consistency (Cronbach's Alfa > 0.7) and strong test-retest reliability (r > 0.6). Confirmatory factor analyses supported the proposed one-factor structure of the CHU9D. For child algorithm, RMSEA = 0.05, CFI = 0.95, TLI = 0.94, and SRMR = 0.04. For adult algorithm RMSEA = 0.04, CFI = 0.96, TLI = 0.95, and SRMR = 0.04. The CHU9D utility value correlated moderately or strongly with KIDSCREEN-10 and PedsQL total scores (r > 0.5-0.7). The CHU9D discriminated as anticipated on health and on three of five sociodemographic characteristics (sex, age, and custody arrangement, but not socioeconomic status and ethnic origin).

Conclusions: This study provides evidence that the Swedish CHU9D is a feasible, reliable and valid measure of preference-based HRQoL in children. The study furthermore suggests that the CHU9D is appropriate for use among children 7-15 years of age in the general population, as well as among subgroups aged 7- 9, 10-12 and 13-15 years.
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http://dx.doi.org/10.1186/s12955-021-01830-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336397PMC
August 2021

The Bidirectional Relationship Between Subjective Well-Being and Academic Achievement in Adolescence.

J Youth Adolesc 2021 May 6;50(5):992-1002. Epub 2021 Mar 6.

Department of Epidemiology and Global Health, Umeå University, SE-901 87, Umeå, Sweden.

The well-being of young people in relation to their school performance has received increased attention in recent years. However, there is a lack of knowledge about the longitudinal and reciprocal relationship between adolescents' subjective well-being and their academic achievements. The current study examined the bidirectional relationship between subjective well-being and academic achievement across two timepoints (T1 and T2) during the course of mid to late adolescence, i.e., in school year 9 (age 15), and school years 11-12 (ages 17-18). The study also investigated variation in the association as a function of adolescent gender. Data on subjective well-being and teacher-assigned school grades of 723 adolescents (48.7% girls) residing in Sweden were analyzed by estimating a series of cross-lagged path models. The findings suggest gender differences in the relationship as no associations were found among boys. Support for a bidirectional relationship between the constructs was only found for girls. For girls, higher subjective well-being at T1 was associated with higher academic achievements at T2, while higher academic achievements at T1 was associated with lower subjective well-being at T2. These findings highlight that the subjective well-being of adolescent girls may be important for their ability to perform at school, but their academic achievements may also inflict negatively on their subjective well-being.
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http://dx.doi.org/10.1007/s10964-021-01413-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043926PMC
May 2021

Hypophosphatemic Hypovitaminosis D Induces Osteomalacia in the Adult Female Rat.

Endocrinology 2020 08;161(8)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D-depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D-depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.
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http://dx.doi.org/10.1210/endocr/bqaa100DOI Listing
August 2020

School-related physical activity interventions and mental health among children: a systematic review and meta-analysis.

Sports Med Open 2020 Jun 16;6(1):25. Epub 2020 Jun 16.

Community Nutrition and Physical Activity, Department of Global Public Health, Karolinska Institutet, Solnavaegen 1E, 104 65, Stockholm, Sweden.

Background: Low levels of physical activity, sedentary behaviour and mental health problems are issues that have received considerable attention in the last decade. The aim of this systematic review and meta-analysis was to investigate effects of interventions targeting school-related physical activity or sedentary behaviour on mental health in children and adolescents and to identify the features of effective interventions.

Methods: Scientific articles published between January 2009 and October 2019 fulfilling the following criteria were included: general populations of children and adolescents between age 4 and 19, all types of school-related efforts to promote physical activity or reduce sedentary behaviour. Study selection, data extraction and quality assessment were done by at least two authors independently of each other. Data were analysed with a random effects meta-analysis and by narrative moderator analyses.

Results: The literature search resulted in 10265 unique articles. Thirty-one articles, describing 30 interventions, were finally included. Eleven relevant outcomes were identified: health-related quality of life, well-being, self-esteem and self-worth, resilience, positive effect, positive mental health, anxiety, depression, emotional problems, negative effect and internalising mental health problems. There was a significant beneficial effect of school-related physical activity interventions on resilience (Hedges' g = 0.748, 95% CI = 0.326; 1.170, p = 0.001), positive mental health (Hedges' g = 0.405, 95% CI = 0.208; 0.603, p = < 0.001), well-being (Hedges' g = 0.877, 95% CI = 0.356; 1.398, p = < 0.001) and anxiety (Hedges' g = 0.347, 95% CI = 0.072; 0.623, p = 0.013). Heterogeneity was moderate to high (I = 59-98%) between studies for all outcomes except positive effect, where heterogeneity was low (I = 2%). The narrative moderator analyses of outcomes based on 10 or more studies showed that age of the children moderated the effect of the intervention on internalising mental health problems. Interventions in younger children showed a significantly negative or no effect on internalising mental health problems while those in older children showed a significant positive or no effect. Moreover, studies with a high implementation reach showed a significant negative or no effect while those with a low level of implementation showed no or a positive effect. No signs of effect moderation were found for self-esteem, well-being or positive mental health. Risk of publication bias was evident for several outcomes, but adjustment did not change the results.

Conclusions: School-related physical activity interventions may reduce anxiety, increase resilience, improve well-being and increase positive mental health in children and adolescents. Considering the positive effects of physical activity on health in general, these findings may reinforce school-based initiatives to increase physical activity. However, the studies show considerable heterogeneity. The results should therefore be interpreted with caution. Future studies should report on implementation factors and more clearly describe the activities of the control group and whether the activity is added to or replacing ordinary physical education lessons in order to aid interpretation of results.

Trial Registration: PROSPERO, CRD42018086757.
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http://dx.doi.org/10.1186/s40798-020-00254-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297899PMC
June 2020

Health-Related Quality of Life in Children With Low Language or Congenital Hearing Loss, as Measured by the PedsQL and Health Utility Index Mark 3.

Value Health 2020 02 10;23(2):164-170. Epub 2019 Oct 10.

Murdoch Children's Research Institute, Parkville, Melbourne, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.

Objectives: To examine health-related quality of life (HRQoL) in young children with low language or congenital hearing loss and to explore the value of assessing HRQoL by concurrently administering 2 HRQoL instruments in populations of children.

Methods: Data were from 2 Australian community-based studies: Language for Learning (children with typical and low language at age 4 years, n = 1012) and the Statewide Comparison of Outcomes study (children with hearing loss, n = 108). HRQoL was measured using the parent-reported Health Utilities Index Mark 3 (HUI3) and the Pediatrics Quality of Life Inventory 4.0 (PedsQL) generic core scale. Agreement between the HRQoL instruments was assessed using intraclass correlation and Bland-Altman plots.

Results: Children with low language and with hearing loss had lower HRQoL than children with normal language; the worst HRQoL was experienced by children with both. The lower HRQoL was mainly due to impaired school functioning (PedsQL) and speech and cognition (HUI3). Children with hearing loss also had impaired physical and social functioning (PedsQL), vision, hearing, dexterity, and ambulation (HUI3). Correlations between instruments were poor to moderate, with low agreement.

Conclusions: Children with low language and congenital hearing loss might benefit from interventions targeting overall health and well-being, not just their impairments. The HUI3 and PedsQL each seemed to provide unique information and thus may supplement each other in assessing HRQoL of young children, including those with low language or congenital hearing loss.
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http://dx.doi.org/10.1016/j.jval.2019.07.019DOI Listing
February 2020

Perceived problems with academic achievement in school-aged children with recurrent pain - a longitudinal study.

Scand J Public Health 2021 Jul 11;49(5):487-494. Epub 2019 Dec 11.

Department of Epidemiology and Global Health, Umeå University, Sweden.

The overall aim was to explore the relationship between recurrent pain and perceived problems with academic achievement among boys and girls in middle and late elementary school. This 3-year follow-up study was based on data from the Study of Health in School-aged Children from Umeå (Sweden) and included children attending grade 6 in years 2003 and 2006, and a follow-up 3 years later in grade 9 ( = 1524, participation rate 90%). Recurrent pain (head, stomach or back) at least doubled the odds of concurrent- and subsequent perceived problems with academic achievement. This applied for pain on a monthly and weekly basis, from single and multiple sites, and from each of the three studied pain sites. The odds increased with increasing pain frequency and number of pain sites. Problems with sleep, concentration or school absenteeism did not explain the association. .
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http://dx.doi.org/10.1177/1403494819889260DOI Listing
July 2021

The interplay between national and parental unemployment in relation to adolescent life satisfaction in 27 countries: analyses of repeated cross-sectional school surveys.

BMC Public Health 2019 Nov 28;19(1):1555. Epub 2019 Nov 28.

Department of Social Work, Umeå University, Umeå, Sweden.

Background: Previous research shows that parental unemployment is associated with low life satisfaction in adolescents. It is unclear whether this translates to an association between national unemployment and adolescent life satisfaction, and whether such a contextual association is entirely explained by parental unemployment, or if it changes as a function thereof. For adults, associations have been shown between unemployment and mental health, including that national unemployment can affect mental health and life satisfaction of both the employed and the unemployed, but to different degrees. The aim of this paper is to analyse how national unemployment levels are related to adolescent life satisfaction, across countries as well as over time within a country, and to what extent and in what ways such an association depends on whether the individual's own parents are unemployed or not.

Methods: Repeated cross-sectional data on adolescents' (aged 11, 13 and 15 years, n = 386,402) life satisfaction and parental unemployment were collected in the Health Behaviour in School-aged Children (HBSC) survey, in 27 countries and 74 country-years, across 2001/02, 2005/06 and 2009/10 survey cycles. We linked this data to national harmonised unemployment rates provided by OECD and tested their associations using multilevel linear regression, including interaction terms between national and parental unemployment.

Results: Higher national unemployment rates were related to lower adolescent life satisfaction, cross-sectionally between countries but not over time within countries. The verified association was significant for adolescents with and without unemployed parents, but stronger so in adolescents with unemployed fathers or both parents unemployed. Having an unemployed father, mother och both parents was in itself related to lower life satisfaction.

Conclusion: Living in a country with higher national unemployment seems to be related to lower adolescent life satisfaction, whether parents are unemployed or not, although stronger among adolescents where the father or both parents are unemployed. However, variation in unemployment over the years did not show an association with adolescent life satisfaction.
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http://dx.doi.org/10.1186/s12889-019-7721-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882305PMC
November 2019

Recurrent Pain and Academic Achievement in School-Aged Children: A Systematic Review.

J Sch Nurs 2020 Feb 20;36(1):61-78. Epub 2019 Feb 20.

Department of Epidemiology and Global Health, Umeå University, Umeå, Sweden.

Recurrent pain and school failures are common problems in children visiting the school nurses office. The overall aim of the current study was to investigate the relationship between recurrent pain and academic achievement in school-aged children. Literature was searched in seven electronic databases and in relevant bibliographies. Study selection, data extraction, and study and evidence quality assessments were performed systematically with standardized tools. Twenty-one studies met the inclusion criteria and 13 verified an association between recurrent pain (headache, stomachache, and musculoskeletal pain) and negative academic achievement. Two longitudinal studies indicated a likely causal effect of pain on academic achievement. All studies had substantial methodological drawbacks and the overall quality of the evidence for the identified associations was low. Thus, children's lack of success in school may be partly attributed to recurrent pain problems. However, more high-quality studies are needed, including on the direction of the association and its moderators and mediators.
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http://dx.doi.org/10.1177/1059840519828057DOI Listing
February 2020

Preteen children's health related quality of life in Sweden: changes over time and disparities between different sociodemographic groups.

BMC Public Health 2019 Jan 31;19(1):139. Epub 2019 Jan 31.

Department of Epidemiology and Global Health, Umeå University, Umeå, Sweden.

Background: Assessing disparities in health-related quality of Life (HRQoL) is important as a part of health-related disparities in the society. The aim of this study was to explore HRQoL among 12-year-olds in Sweden in terms of differences between years 2005 and 2009 and disparities related to sociodemographic background.

Methods: During the school years 2005 and 2009, a total of 18,325 sixth grade students in Sweden were invited to a celiac disease screening study; 13,279 agreed to participate. Jointly with the celiac screening, the children answered a questionnaire that included EuroQol 5 Dimensions-youth (EQ-5D-Y) and their parents responded to separate questionnaires about their own and their child's country of birth, family structure, their employment status, occupation, and education. In total 11,009 child-parent questionnaires were collected. Logistic regression was used to study differences in HRQoL between 2005 and 2009, and between various sociodemographic subgroups.

Results: Compared with 2005, children in 2009 reported more pain (OR: 1.20, 95% CI: 1.1-1.3) and more mood problems (OR: 1.35, 95% CI: 1.2-1.5). In general, girls reported more pain and mood problems and had more disparities than boys. There were no significant differences based on parents' occupation, however, children of parents with low or medium education levels reported less "mood problems" than those of parents with high education levels (OR: 0.65, 95% CI: 0.46-0.92) and (OR: 0.84, 95% CI: 0.73-0.96), respectively. A slight variation was seen in HRQoL between children with different migration background. Girls living in small municipalities reported more pain (OR: 1.51, 95% CI: 1.14-2.01), and problems performing usual activities (OR: 3.77, 95% CI: 2.08-6.84), compared to girls living in large municipalities. In addition, children living with two parents had less mood problems than children living in other family constellations.

Conclusion: More children reported pain and mood problems in 2009 compared with 2005. To study future trends, health outcomes among children in Sweden should continue to be reported periodically. More efforts should be invested to increase the awareness of health-related disparities as highlighted in this study especially for girls living in small municipalities and children of parents with high education level.
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http://dx.doi.org/10.1186/s12889-019-6429-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357483PMC
January 2019

School experiences in relation to emotional and conduct problems in adolescence: a 3-year follow up study.

Eur J Public Health 2019 06;29(3):436-441

Department of Public Health and Clinical Medicine, Epidemiology and Global Health Unit, Umeå University, Umea, Sweden.

Background: Mental health in adolescents has become a major public health issue. This study examined school experiences in relation to mental health (emotional problems and conduct problems) from early to middle adolescence.

Methods: This longitudinal 3-year follow up study used data from the Swedish Study of Health in School Children in Umeå. Analyses were conducted in 1379 participants that were attending grade six in 2003 or 2006 (age 12 years). KIDSCREEN-52 was used to assess school experiences and the Strengths and Difficulties Questionnaire for emotional and conduct problems. Statistical analyses included repeated measures ANOVA and multiple linear regressions.

Results: Positive school experiences decreased while emotional and conduct problem scores increased from grades six to nine. Positive school experiences were negatively associated with emotional and conduct problem scores and contributed to the explanation of mental health scores in middle adolescence after controlling for background factors. When baseline mental health problem scores were taken into account the association with early school experiences disappeared (except for conduct problems in boys). However, incorporating concurrent school experiences in the analysis increased the levels of explanation for emotional and conduct problem scores further.

Conclusions: The results of this study confirm that school experiences are linked to emotional and conduct problems. That link may be stronger for conduct problems. In addition, the association of school experiences in early adolescence with later mental health may be overridden by concurrent school experiences in middle adolescence.
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http://dx.doi.org/10.1093/eurpub/cky244DOI Listing
June 2019

Education system stratification and health complaints among school-aged children.

Soc Sci Med 2019 01 8;220:159-166. Epub 2018 Nov 8.

Department of Public Health and Clinical Medicine, Umeå University, University Hospital, 901 85, Umeå, Sweden.

Research shows that the school environment is an important social determinant of health among children and adolescents. However, we know virtually nothing of the health consequences of national education systems and policies, for example the stratification of pupils by academic ability. This study aimed to investigate if education system stratification is related to self-reported psychological and somatic health complaints of pupils aged 11 to 15, and social inequalities in such health complaints. Survey data from the Health Behaviors of School-aged Children (HBSC) survey, covering 33 countries and more than 180 000 pupils in primary and lower secondary school, were used. Multilevel models showed that education system stratification was not associated with the average levels of health complaints of pupils, but cross-level interaction effects showed that stratification moderated the relationship between social background and health complaints, such that inequalities in health complaints were smaller in countries with more stratified systems. Moreover, this moderating effect was mediated by the school learning environment and social relations in school. Specifically, social inequalities in school pressure, academic self-concept, school climate, and school satisfaction were smaller in more stratified education systems, which in turn accounted for smaller inequalities in health complaints in these countries.
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http://dx.doi.org/10.1016/j.socscimed.2018.11.007DOI Listing
January 2019

Correction to: Health-related quality of life in girls and boys with juvenile idiopathic arthritis: self- and parental reports in a cross-sectional study.

Pediatr Rheumatol Online J 2018 08 22;16(1):53. Epub 2018 Aug 22.

Department of Public health and Clinical medicine, Epidemiology and Global health, Umeå University, Umeå, Sweden.

Following publication of the original article [1], the authors reported an error in the data of their article: one girl was by mistake scored as a boy. The authors have made new analyses of the corrected data. The corrected data and the new analyses are listed in this Correction.
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http://dx.doi.org/10.1186/s12969-018-0269-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106743PMC
August 2018

Correction to: Health-related quality of life in girls and boys with juvenile idiopathic arthritis: self- and parental reports in a cross-sectional study.

Pediatr Rheumatol Online J 2018 08 22;16(1):53. Epub 2018 Aug 22.

Department of Public health and Clinical medicine, Epidemiology and Global health, Umeå University, Umeå, Sweden.

Following publication of the original article [1], the authors reported an error in the data of their article: one girl was by mistake scored as a boy. The authors have made new analyses of the corrected data. The corrected data and the new analyses are listed in this Correction.
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http://dx.doi.org/10.1186/s12969-018-0269-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106743PMC
August 2018

Authors' response to Letter to the Editor: ANZJPH-2017-220.

Aust N Z J Public Health 2018 04 27;42(2):215. Epub 2017 Dec 27.

Centre for Population Health Research, Deakin University, Victoria.

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http://dx.doi.org/10.1111/1753-6405.12767DOI Listing
April 2018

Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor.

Purinergic Signal 2017 Dec 21;13(4):545-557. Epub 2017 Aug 21.

College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling. One receptor subtype, which has been suggested to be involved in this regulation, is the P2Y2 receptor (P2Y2R). In the present study, we investigated the effect of P2Y2R overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces. Both mineral apposition rate and thickness of the endocortical osteoid layer were higher in the P2Y2R-Tg rats. μCT analysis showed reduced trabecular thickness and structural model index in P2Y2R-Tg rats. Femoral length was increased in the P2Y2R-Tg rats compared to Wt rats. In vitro, there was an increased formation of osteoclasts, but no change in total resorption in cultures from P2Y2R-Tg rats. The formation of mineralized nodules was significantly reduced in the osteoblastic cultures from P2Y2R-Tg rats. In conclusion, our study suggests that P2Y2R is involved in regulation of bone turnover, due to the effects on both osteoblasts and osteoclasts and that these effects might be relevant in the regulation of bone growth.
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http://dx.doi.org/10.1007/s11302-017-9582-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714845PMC
December 2017

School-based systems change for obesity prevention in adolescents: outcomes of the Australian Capital Territory 'It's Your Move!'

Aust N Z J Public Health 2017 Oct 27;41(5):490-496. Epub 2017 Jul 27.

Centre for Population Health Research, Deakin University, Victoria.

Objective: The Australian Capital Territory 'It's Your Move!' (ACT-IYM) was a three-year (2012-2014) systems intervention to prevent obesity among adolescents.

Methods: The ACT-IYM project involved three intervention schools and three comparison schools and targeted secondary students aged 12-16 years. The intervention consisted of multiple initiatives at individual, community, and school policy level to support healthier nutrition and physical activity. Intervention school-specific objectives related to increasing active transport, increasing time spent physically active at school, and supporting mental wellbeing. Data were collected in 2012 and 2014 from 656 students. Anthropometric data were objectively measured and behavioural data self-reported.

Results: Proportions of overweight or obesity were similar over time within the intervention (24.5% baseline and 22.8% follow-up) and comparison groups (31.8% baseline and 30.6% follow-up). Within schools, two of three the intervention schools showed a significant decrease in the prevalence of overweight and obesity (p<0.05).

Conclusions: There was some evidence of effectiveness of the systems approach to preventing obesity among adolescents. Implications for public health: The incorporation of systems thinking has been touted as the next stage in obesity prevention and public health more broadly. These findings demonstrate that the use of systems methods can be effective on a small scale.
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http://dx.doi.org/10.1111/1753-6405.12696DOI Listing
October 2017

P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts.

Bone 2017 02 14;95:91-101. Epub 2016 Nov 14.

Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark; OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address:

The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling. We report that osteoblasts derived from human trabecular explants express a functional P2X7R capable of agonist-induced increase in intracellular calcium concentration and a positive permeability to fluorescent dyes. These osteoblasts are fully differentiated cells with alkaline phosphatase activity and the ability to form mineralized nodules. We show that the transcriptional regulation of osteoblastic markers can be modulated by P2X7R activity or blockade thereby influencing the differentiation, proliferation and bone matrix formation by these primary human osteoblasts. Finally, we demonstrate that the P2X7R is involved in propagation of mechanically-induced intercellular signaling in addition to the known mechanisms involving calcium signaling via P2Y2 receptors and gap junction.
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http://dx.doi.org/10.1016/j.bone.2016.11.011DOI Listing
February 2017

The Cross-Sectional Association between Diet Quality and Depressive Symptomology amongst Fijian Adolescents.

PLoS One 2016 25;11(8):e0161709. Epub 2016 Aug 25.

World Health Organization Collaborating Centre for Obesity Prevention, Deakin University, Geelong, Victoria, Australia.

Objective: To examine the relationship between diet quality and depressive symptomology amongst a community-based sample of Fijian adolescents.

Methods: Participants included 7,237 adolescents (52.6% girls; mean age 15.6 years) at baseline (2005) and 2,948 (56% girls; mean age 17.4 years) at follow-up (2007/2008), from the Pacific Obesity Prevention in Communities Project. Intervention schools (n = 7) were selected from Nasinu, near Suva on the main Fijian island Viti Levu, and comparison schools (n = 11) were chosen from towns on the opposite, west side of the island. A dietary questionnaire was used to measure diet quality. Factor analysis clustered dietary variables into two unique and independent factors, referred to as healthy diet quality and unhealthy diet quality. Depressive symptomology was assessed via the emotional subscale of the Paediatric Quality of Life Inventory. Both measures were self-reported and self-administered. Multiple linear regression was used to test cross-sectional associations (at baseline and follow-up) between diet quality and depressive symptomology. Variables controlled for included gender, age, ethnicity, study condition, BMI-z scores, and physical activity.

Findings: Strong, positive dose-response associations between healthy diet and high emotional scores (lower depressive symptomology) were found in cross-sectional analyses at baseline and follow-up, among boys and girls. No association was found between emotional health and unhealthy diet.

Conclusions: This study suggests that cross-sectional relationships exist between a high quality diet during adolescence and less depressive symptoms, however more evidence is required to determine if these two variables are linked causally. Trial population health strategies that use dietary interventions as a mechanism for mental health promotion provide an opportunity to further test these associations. If this is indeed a true relationship, these forms of interventions have the potential to be inexpensive and have substantial reach, especially in Low and Middle Income Countries.

Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12608000345381.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161709PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999057PMC
July 2017

School experiences may be important determinants of mental health problems in middle childhood - a Swedish longitudinal population-based study.

Acta Paediatr 2016 Apr 2;105(4):407-15. Epub 2016 Feb 2.

Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.

Aim: Little is known about the association between school experiences and mental health in young schoolchildren. This study explored the cross-sectional and prospective associations between children's school experiences and mental health in middle childhood.

Methods: We gathered comprehensive population-based data on the school experiences and mental health of 592 schoolchildren attending grades three and six in Sweden (ages approximately nine and 12 years). The KIDSCREEN questionnaire was used to measure school experiences in both age groups while the Child Behavior Checklist and the Strengths and Difficulties Questionnaire measured mental health in grades three and six, respectively.

Results: Children with problematic school experiences in grade three had an approximately two times higher odds for concurrent total, internalised, externalised, attention-hyperactivity and social problems. They also had a 1.5-2.5 higher odds for these mental health problems three years later. Likewise, there was an association between problematic school experiences in grade three and lower levels of prosocial behaviour three years later. These associations were shown in both boys and girls, but were particularly pronounced in girls.

Conclusion: This study indicated that school experiences in young schoolchildren may be important determinants of concurrent and later mental health problems.
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http://dx.doi.org/10.1111/apa.13326DOI Listing
April 2016

Mental problems and their socio-demographic determinants in young schoolchildren in Sweden, a country with high gender and income equality.

Scand J Public Health 2016 Feb 21;44(1):18-26. Epub 2015 Sep 21.

Department of Public Health and Clinical Medicine, Unit of Epidemiology and Global Health, Umeå University, Sweden.

Aims: Mental problems and their potential socio-demographic determinants were investigated in young schoolchildren in Sweden, a high-income country in the top of income- and gender-equality rankings.

Methods: Cross-sectional study of 1465 schoolchildren in grades 3 and 6. Mental health was measured by the Child Behavior Checklist and the Youth Self Report (Total problems and 14 specific problem areas). Potential socio-demographic determinants were sex, parental education and occupation, family structure, and immigrant status.

Results: Mental problems were present in 14% of the sixth graders and in 7% of the third graders. In grade 3, the mean total problem score was lower in girls than in boys, but the prevalence of problems at a subclinical/clinical level did not differ by sex. Furthermore, in nine to 13 of the 14 specific problem areas, problems were equally distributed by sex, parental education, parental occupation, immigrant status, and family structure. In grade 6, both the total mean score and the overall odds of subclinical/clinical problems were similar in girls and boys. Likewise, in all the specific problem areas, problems were evenly distributed by parental education and occupation, and only independently associated with immigrant status and family structure in one problem area. In five specific problem areas, boys had higher odds of problems than girls.

Conclusions: This study shows that also in a relatively wealthy and equal country such as Sweden, mental problems are a significant child public health issue. The association between socio-demographic background and mental problems seems to be rather weak, but differ dependent on the type of mental problem in focus.
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http://dx.doi.org/10.1177/1403494815603544DOI Listing
February 2016

Health-related quality of life in indigenous Sami schoolchildren in Sweden.

Acta Paediatr 2015 Jan 7;104(1):75-83. Epub 2014 Oct 7.

Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden.

Aim: To investigate health-related quality of life (HRQOL) in indigenous Sami schoolchildren in Sweden and its associations with sex, age, enculturation and ethnicity-related negative treatment.

Methods: The study population was comprised of all children in grades 6-12 (ages 12-18 years) who attended specific Sami school programmes in Sweden. HRQOL was measured by the Kidscreen-52 self-report form, which was filled in at school (n = 121).

Results: The indigenous Sami children in Sweden experienced lower HRQOL than Swedish children in general, with regard to their school situation, financial resources, parents' relations, physical well-being and social support from peers. In Sami children, functioning and well-being generally decreased by older age group and girls reported lower physical well-being, more negative feelings and more negative self-perception than boys. Finally, more than half of the Sami children had experienced ethnicity-related negative treatment, and these children reported a robustly lower functioning and well-being compared with those without this experience.

Conclusion: In some aspects of HRQOL, indigenous Sami schoolchildren with an explicit ethnic identity experienced less favourable functioning and well-being than Swedish children in general, which is worrisome. A high degree of ethnicity-related negative treatment may partly explain this lower HRQOL in Sami children.
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http://dx.doi.org/10.1111/apa.12786DOI Listing
January 2015

Low health-related quality of life in school-aged children in Tonga, a lower-middle income country in the South Pacific.

Glob Health Action 2014 20;7:24896. Epub 2014 Aug 20.

Deakin Health Economics, Faculty of Health, Deakin University, Burwood, Victoria, Australia.

Background: Ensuring a good life for all parts of the population, including children, is high on the public health agenda in most countries around the world. Information about children's perception of their health-related quality of life (HRQoL) and its socio-demographic distribution is, however, limited and almost exclusively reliant on data from Western higher income countries.

Objectives: To investigate HRQoL in schoolchildren in Tonga, a lower income South Pacific Island country, and to compare this to HRQoL of children in other countries, including Tongan children living in New Zealand, a high-income country in the same region.

Design: A cross-sectional study from Tonga addressing all secondary schoolchildren (11-18 years old) on the outer island of Vava'u and in three districts of the main island of Tongatapu (2,164 participants). A comparison group drawn from the literature comprised children in 18 higher income and one lower income country (Fiji). A specific New Zealand comparison group involved all children of Tongan descendent at six South Auckland secondary schools (830 participants). HRQoL was assessed by the self-report Pediatric Quality of Life Inventory 4.0.

Results: HRQoL in Tonga was overall similar in girls and boys, but somewhat lower in children below 15 years of age. The children in Tonga experienced lower HRQoL than the children in all of the 19 comparison countries, with a large difference between children in Tonga and the higher income countries (Cohen's d 1.0) and a small difference between Tonga and the lower income country Fiji (Cohen's d 0.3). The children in Tonga also experienced lower HRQoL than Tongan children living in New Zealand (Cohen's d 0.6).

Conclusion: The results reveal worrisome low HRQoL in children in Tonga and point towards a potential general pattern of low HRQoL in children living in lower income countries, or, alternatively, in the South Pacific Island countries.
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http://dx.doi.org/10.3402/gha.v7.24896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141941PMC
April 2015

Health-related quality of life is not impaired in children with undetected as well as diagnosed celiac disease: a large population based cross-sectional study.

BMC Public Health 2014 May 5;14:425. Epub 2014 May 5.

Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.

Background: Knowledge regarding the health-related quality of life (HRQoL) of children with celiac disease remains limited and inconclusive. We investigated the HRQoL of three groups of 12-year-olds with: i) undetected celiac disease ii) clinically diagnosed celiac disease, and iii) without celiac disease.

Methods: A school-based cross-sectional multicenter screening study invited 18 325 children, whereof 68% consented to participate. Participants provided a blood sample, which was later analyzed for anti-tissue-tranglutaminase antibodies, and alongside filled in a questionnaire. When anti-tissue-tranglutaminase antibodies were elevated, a small intestinal biopsy verified the screening-detected celiac disease diagnosis. Self-reported HRQoL was measured using Kidscreen, a generic 52 items instrument with proven reliability and validity. Scores were linearly transformed into a 0-100 scale with higher values indicating better HRQoL. Mean values with standard deviations (mean ± SD) were compared, and uni- and multivariate logistic regression models tested the odds of a low HRQoL among children with undetected or diagnosed celiac disease, respectively.

Results: Children with undetected celiac disease (n = 238) reported similar HRQoL as children without celiac disease (n = 12 037) (83.0 ± 11.0 vs. 82.5 ± 11.3, P = 0.51), and also similar HRQoL (82.2 ± 12.2, P = 0.28) to that of children with diagnosed celiac disease (n = 90), of whom 92% were adherent to treatment. Having undetected celiac disease did not increase the odds of low overall HRQoL, independent of sex, area of residence, study year and occurrence of gastrointestinal symptoms (adjusted odds ratio 0.77, 95% CI 0.54-1.10). Comparable results were seen for diagnosed celiac disease cases (adjusted odds ratio 1.11, 95% CI 0.67-1.85).

Conclusion: Children with undetected celiac disease reported comparable HRQoL as their peers with diagnosed celiac disease, and those without celiac disease, when reporting prior to receiving the diagnosis through screening. Thus, children with celiac disease, both untreated and diagnosed, perceive their HRQoL as unimpaired by their disease.
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http://dx.doi.org/10.1186/1471-2458-14-425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021079PMC
May 2014

Parental encouragement of healthy behaviors: adolescent weight status and health-related quality of life.

BMC Public Health 2014 Apr 16;14:369. Epub 2014 Apr 16.

School of Psychology, Faculty of Health, Deakin University, 221 Burwood Highway, Burwood, Vic 3125, Australia.

Background: Obesity is a major health concern for adolescents, with one in four being overweight or obese in Australia. The purpose of this study was to examine the moderation effect of parental encouragement of healthy behaviors on the relationship between adolescent weight status and Health-Related Quality of Life (HRQoL).

Methods: Baseline data were collected from 3,040 adolescents participating in the It's Your Move project, conducted in the Barwon South-West region of Victoria, in 2005. The Paediatric Quality of Life Inventory was used to measure HRQoL, and parental encouragement was derived from purposely designed self-report items. Weight status was calculated according to World Health Organization growth standards from measured weight and height. Linear regression analyses modeled direct relationships and interaction terms. Analyses were adjusted for age, sex, physical activity level, nutrition and school attended.

Results: Higher levels of parental encouragement, as compared to low encouragement, were positively associated with higher global HRQoL scores, particularly in the physical functioning domain. To a lesser degree, high parental encouragement was also associated with higher scores on the psychosocial domain. Obese weight status showed a significant association with lower HRQoL on all scales. Parental encouragement significantly moderated the inverse relationship between overweight status and physical wellbeing.

Conclusions: Findings suggest that parental encouragement of healthy behavior is associated with increased HRQoL scores for adolescents. Whilst more research is needed to validate the significant interaction effect, main effects suggest that parental encouragement of healthy behavior is an important factor in adolescent wellbeing and should be considered when developing prevention and clinical interventions for obesity.
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http://dx.doi.org/10.1186/1471-2458-14-369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996491PMC
April 2014

The effect of PTH(1-34) on fracture healing during different loading conditions.

J Bone Miner Res 2013 Oct;28(10):2145-55

Research Center of Ageing and Osteoporosis, Department of Medicine and Diagnostics, Copenhagen University Hospital, Glostrup, Denmark.

Parathyroid hormone (PTH) and PTH(1-34) have been shown to promote bone healing in several animal studies. It is known that the mechanical environment is important in fracture healing. Furthermore, PTH and mechanical loading has been suggested to have synergistic effects on intact bone. The aim of the present study was to investigate whether the effect of PTH(1-34) on fracture healing in rats was influenced by reduced mechanical loading. For this purpose, we used female, 25-week-old ovariectomized rats. Animals were subjected to closed midshaft fracture of the right tibia 10 weeks after ovariectomy. Five days before fracture, half of the animals received Botulinum Toxin A injections in the muscles of the fractured leg to induce muscle paralysis (unloaded group), whereas the other half received saline injections (control group). For the following 8 weeks, half of the animals in each group received injections of hPTH(1-34) (20 µg/kg/day) and the other half received vehicle treatment. Fracture healing was assessed by radiology, dual-energy X-ray absorptiometry (DXA), histology, and bone strength analysis. We found that unloading reduced callus area significantly, whereas no effects of PTH(1-34) on callus area were seen in neither normally nor unloaded animals. PTH(1-34) increased callus bone mineral density (BMD) and bone mineral content (BMC) significantly, whereas unloading decreased callus BMD and BMC significantly. PTH(1-34) treatment increased bone volume of the callus in both unloaded and control animals. PTH(1-34) treatment increased ultimate force of the fracture by 63% in both control and unloaded animals and no interaction of the two interventions could be detected. PTH(1-34) was able to stimulate bone formation in normally loaded as well as unloaded intact bone. In conclusion, the study confirms the stimulatory effect of PTH(1-34) on fracture healing, and our data suggest that PTH(1-34) is able to promote fracture healing, as well as intact bone formation during conditions of reduced mechanical loading.
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http://dx.doi.org/10.1002/jbmr.1957DOI Listing
October 2013

Health-related quality of life is low in secondary school children in fiji.

Int J Pediatr 2012 4;2012:294530. Epub 2012 Dec 4.

Deakin Health Economics, Faculty of Health, Deakin University, 221 Burwood Highway, Melbourne, VIC 3125, Australia ; Clinical Sciences, Umeå University, 90187 Umeå, Sweden.

The health and wellbeing of children in lower-income countries is the focus of much international effort, yet there has been very little direct measurement of this. Objective. The current objective was to study the health-related quality of life (HRQoL) in a general population of secondary school children in Fiji, a low middle-income country in the Pacific. Methods. Self-reported HRQoL was measured by the Pediatric Quality of Life Inventory 4.0 in 8947 school children (aged 12-18 years) from 18 secondary schools on Viti Levu, the main island of Fiji. HRQoL in Fiji was compared to that of school-aged children in 13 high- and upper middle-income countries. Results. The school children in Fiji had lower HRQoL than the children in the 13 comparison countries, with consistently lower physical, emotional, social, and school functioning and wellbeing. HRQoL was particularly low amongst girls and Indigenous Fijians. Conclusions. These findings raise concerns about the general functioning and wellbeing of school children in Fiji. The consistently low HRQoL across all core domains suggests pervasive underlying determinants. Investigation of the potential determinants in Fiji and validation of the current results in Fiji and other lower-income countries are important avenues for future research.
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http://dx.doi.org/10.1155/2012/294530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523139PMC
January 2013

Health-related quality of life in girls and boys with juvenile idiopathic arthritis: self- and parental reports in a cross-sectional study.

Pediatr Rheumatol Online J 2012 Sep 17;10(1):33. Epub 2012 Sep 17.

Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.

Unlabelled:

Background: Juvenile Idiopathic Arthritis (JIA) affects children and adolescents with both short-term and long-term disability. These children also report lower health-related quality of life (HRQOL) compared to their healthy peers. However, there seems to be some discrepancies between self- and parent-reports, and gender differences need to be further studied. This study aims to describe HRQOL in girls and boys with JIA, and to explore gender differences in self-reports compared to parent-reports of HRQOL in children with JIA.

Methods: Fifty-three children and adolescents with JIA (70% girls and 30% boys) with a median age of 14 years (8-18 years), and their parents, participated in this cross-sectional study in Sweden. Data was systematically collected prior to ordinary visits at a Pediatric outpatient clinic, during a period of 16 months (2009-2010). Disability was assessed with the Childhood Health Assessment Questionnaire (CHAQ), and disease activity by physicians' assessments and Erythrocyte Sedimentation Rate (ESR). The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) was used to assess self- and parent-reports of HRQOL in the child.

Results: In this sample of children with generally low disease activity and mild to moderate disability, more than half of the children experienced suboptimal HRQOL, equally in girls and boys. Significant differences between self- and parent-reports of child HRQOL were most evident among girls, with lower parent-reports regarding the girl's physical- and psychosocial health as well as in the total HRQOL score. Except for the social functioning subscale, where parents' reports were higher compared to their sons, there were no significant differences between boys- and parent-reports.

Conclusions: More than half of the girls and boys experienced suboptimal HRQOL in this sample, with no gender differences. However, there were differences between self- and parent-reports of child HRQOL, with most significant differences found among the girls. Thus, differences between self- and parent-reports of child HRQOL must be taken into account in clinical settings, especially among girls with JIA.
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http://dx.doi.org/10.1186/1546-0096-10-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523024PMC
September 2012

Genetic Background Strongly Influences the Bone Phenotype of P2X7 Receptor Knockout Mice.

J Osteoporos 2012 9;2012:391097. Epub 2012 Aug 9.

Departments of Diagnostics and Medicine, Research Centre of Ageing and Osteoporosis, Glostrup University Hospital, 2600 Glostrup, Denmark.

The purinergic P2X7 receptor is expressed by bone cells and has been shown to be important in both bone formation and bone resorption. In this study we investigated the importance of the genetic background of the mouse strains on which the P2X7 knock-out models were based by comparing bone status of a new BALB/cJ P2X7(-/-) strain with a previous one based on the C57BL/6 strain. Female four-month-old mice from both strains were DXA scanned on a PIXImus densitometer; femurs were collected for bone strength measurements and serum for bone marker analysis. Bone-related parameters that were altered only slightly in the B6 P2X7(-/-) became significantly altered in the BALB/cJ P2X7(-/-) when compared to their wild type littermates. The BALB/cJ P2X7(-/-) showed reduced levels of serum C-telopeptide fragment (s-CTX), higher bone mineral density, and increased bone strength compared to the wild type littermates. In conclusion, we have shown that the genetic background of P2X7(-/-) mice strongly influences the bone phenotype of the P2X7(-/-) mice and that P2X7 has a more significant regulatory role in bone remodeling than found in previous studies.
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http://dx.doi.org/10.1155/2012/391097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425798PMC
August 2012

Association between P2X7 Receptor Polymorphisms and Bone Status in Mice.

J Osteoporos 2012 5;2012:637986. Epub 2012 Aug 5.

Research Centre of Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup University Hospital, 2600 Glostrup, Denmark.

Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA), bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ) had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX) compared to C57Bl/6 (B6) and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.
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http://dx.doi.org/10.1155/2012/637986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420134PMC
August 2012

Association of P2Y(2) receptor SNPs with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients.

Purinergic Signal 2013 Mar 8;9(1):41-9. Epub 2012 Jul 8.

Department of Epidemiology, School for Public Health and Primary Care (CAPHRI), Maastricht University, Peter Debyeplein 1, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

The P2Y(2) receptor is a G-protein-coupled receptor with adenosine 5'-triphosphate (and UTP) as natural ligands. It is thought to be involved in bone physiology in an anti-osteogenic manner. As several non-synonymous single nucleotide polymorphisms (SNPs) have been identified within the P2Y(2) receptor gene in humans, we examined associations between genetic variations in the P2Y(2) receptor gene and bone mineral density (BMD) (i.e., osteoporosis risk), in a cohort of fracture patients. Six hundred and ninety women and 231 men aged ≥50 years, visiting an osteoporosis outpatient clinic at Maastricht University Medical Centre for standard medical follow-up after a recent fracture, were genotyped for three non-synonymous P2Y(2) receptor gene SNPs. BMD was measured at three locations (total hip, lumbar spine, and femoral neck) using dual-energy X-ray absorptiometry. Differences in BMD between different genotypes were tested using analysis of covariance. In women, BMD values at all sites were significantly different between the genotypes for the Leu46Pro polymorphism, with women homozygous for the variant allele showing the highest BMD values (0.05 > p > 0.01). The Arg312Ser and Arg334Cys polymorphisms showed no differences in BMD values between the different genotypes. This is the first report that describes the association between the Leu46Pro polymorphism of the human P2Y(2) receptor and the risk of osteoporosis.
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http://dx.doi.org/10.1007/s11302-012-9326-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568433PMC
March 2013
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