The role of lean body mass and physical activity in bone health in children

Baptista, Fátima; Barrigas, Carlos; Vieira, Filomena; Santa-Clara, Helena; Homens, Pedro Mil; Fragoso, Isabel; Teixeira, Pedro J.; Sardinha, Luís B.

doi:10.1007/s00774-011-0294-4

Cited by 59 publications

(56 citation statements)

References 47 publications

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“…Given the established crosstalk between exercise, metabolism and the musculoskeletal system[22,23], we examined the effects of IL15/IL15RA signaling on bone mineralization and osteoblast function in a mouse model lacking Il15ra (Il15ra −/− ). Using ex vivo bone imaging, mechanical testing and histological analysis, we evaluated bone mineralization and morphogenesis in Il15ra −/− femurs.…”

Section: Introductionmentioning

confidence: 99%

IL15RA is required for osteoblast function and bone mineralization

Loro

Ramaswamy

Chandra

et al. 2017

Bone

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Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15ra−/−) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function. We show that lack of IL15RA decreased bone mineralization in vivo and in isolated primary osteogenic cultures, suggesting a cell-autonomous effect. Il15ra−/− osteogenic cultures also had reduced Rankl/Opg mRNA ratio, indicating defective osteoblast/osteoclast coupling. We analyzed the transcriptome of primary pre-osteoblasts from normal and Il15ra−/− mice and identified 1150 genes that were differentially expressed at a FDR of 5%. Of these, 844 transcripts were upregulated and 306 were downregulated in Il15ra−/− cells. The largest functional clusters, highlighted using DAVID analysis, were related to metabolism, immune response, bone mineralization and morphogenesis. The transcriptome analysis was validated by qPCR of some of the most significant hits. Using bioinformatic approaches, we identified candidate genes, including Cd200 and Enpp1, that could contribute to the reduced mineralization. Silencing Il15ra using shRNA in the calvarial osteoblast MC3T3-E1 cell line decreased ENPP1 activity. Taken together, these data support that IL15RA plays a cell-autonomous role in osteoblast function and bone mineralization.

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Section: Introductionmentioning

confidence: 99%

IL15RA is required for osteoblast function and bone mineralization

Loro

Ramaswamy

Chandra

et al. 2017

Bone

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“…Twenty-five to forty minutes of vigorous PA per day has been suggested as a minimum daily dose for optimal bone growth [23]–[26] but the relationship between bone mineral accrual and PA during the growing years has not been thoroughly examined. Of the studies that exist, there is a lack of consensus on whether sex moderates the association between mechanical loading and bone accrual at the proximal femur [18], [19], [27], [28].…”

Section: Introductionmentioning

confidence: 99%

“…However, it has been suggested that the proximal femur of boys’ is more sensitive to mechanical loading than girls’ [27]. This idea was not derived from work specifically powered to examine sex differences [23], [27]–[31]. Furthermore, most studies reporting a lower responsiveness of PA in girls (when compared to boys) analysed only the femoral neck and not other sub-regions of the proximal femur (i.e.…”

Section: Introductionmentioning

confidence: 99%

Sex Specific Association of Physical Activity on Proximal Femur BMD in 9 to 10 Year-Old Children

et al. 2012

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The results of physical activity (PA) intervention studies suggest that adaptation to mechanical loading at the femoral neck (FN) is weaker in girls than in boys. Less is known about gender differences associated with non-targeted PA levels at the FN or other clinically relevant regions of the proximal femur. Understanding sex-specific relationships between proximal femur sensitivity and mechanical loading during non-targeted PA is critical to planning appropriate public health interventions. We examined sex-specific associations between non-target PA and bone mineral density (BMD) of three sub-regions of the proximal femur in pre- and early-pubertal boys and girls. BMD at the FN, trochanter (TR) and intertrochanter (IT) regions, and lean mass of the whole body were assessed using dual-energy x-ray absorptiometry in 161 girls (age: 9.7±0.3 yrs) and 164 boys (age: 9.7±0.3 yrs). PA was measured using accelerometry. Multiple linear regression analyses (adjusted for body height, total lean mass and pubertal status) revealed that vigorous PA explained 3–5% of the variability in BMD at all three sub-regions in boys. In girls, vigorous PA explained 4% of the variability in IT BMD and 6% in TR BMD. PA did not contribute to the variance in FN BMD in girls. An additional 10 minutes per day of vigorous PA would be expected to result in a ∼1% higher FN, TR, and IT BMD in boys (p<0.05) and a ∼2% higher IT and TR BMD in girls. In conclusion, vigorous PA can be expected to contribute positively to bone health outcomes for boys and girls. However, the association of vigorous PA to sub-regions of the proximal femur varies by sex, such that girlś associations are heterogeneous and the lowest at the FN, but stronger at the TR and the IT, when compared to boys.

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“…Body lean mass and bone size are closely related (Ferretti et al 2003; Ferretti et al 2001; Cointry et al 2004). It has been demonstrated that lean mass can predict bone size in pre-pubertal children and can serve as a major determinant of bone size (Martin 2002; Micklesfield et al 2011; Baptista et al 2012). Bone size, in turn, has been shown to be adapted to the dynamic load imposed by muscle force.…”

Section: Introductionmentioning

confidence: 99%

Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study

et al. 2012

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Objective Bone and muscle, two major tissue types of musculoskeletal system, have strong genetic determination. Abnormality in bone and/or muscle may cause musculoskeletal diseases such as osteoporosis and sarcopenia. Bone size phenotypes (BSPs), such as hip bone size (HBS), appendicular bone size (ABS), are genetically correlated with body lean mass (mainly muscle mass). However, the specific genes shared by these phenotypes are largely unknown. In this study, we aimed to identify the specific genes with pleiotropic effects on BSPs and appendicular lean mass (ALM). Methods We performed a bivariate genome-wide association study (GWAS) by analyzing ~690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) followed by a replication study in 2,286 unrelated US Caucasians (558 males and 1728 females). Results We identified 14 interesting single nucleotide polymorphisms (SNPs) that may contribute to variation of both BSPs and ALM, with p values <10−6 in discovery stage. Among them, the association of three SNPs (rs2507838, rs7116722, and rs11826261) in/near GLYAT (glycine-N-acyltransferase) gene was replicated in US Caucasians, with p values ranging from 1.89×10−3 to 3.71×10−4 for ALM-ABS, from 5.14×10−3 to 1.11×10−2 for ALM-HBS, respectively. Meta-analyses yielded stronger association signals for rs2507838, rs7116722, and rs11826261, with pooled p values of 1.68×10−8, 7.94×10−8, 6.80×10−8 for ALB-ABS and 1.22×10−4, 9.85×10−5, 3.96×10−4 for ALM-HBS, respectively. Haplotype allele ATA based on these three SNPs were also associated with ALM-HBS and ALM-ABS in both discovery and replication samples. Interestingly, GLYAT was previously found to be essential to glucose metabolism and energy metabolism, suggesting the gene’s dual role in both bone development and muscle growth. Conclusions Our findings, together with the prior biological evidence, suggest the importance of GLYAT gene in co-regulation of bone phenotypes and body lean mass.

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The role of lean body mass and physical activity in bone health in children

Cited by 59 publications

References 47 publications

IL15RA is required for osteoblast function and bone mineralization

IL15RA is required for osteoblast function and bone mineralization

Sex Specific Association of Physical Activity on Proximal Femur BMD in 9 to 10 Year-Old Children

Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study

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