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Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood
Jonathan A Mitchell1,2, Alessandra Chesi3, Okan Elci4
1Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Insights
Physical activity (PA) benefits childhood bone mineral density (BMD) regardless of genetic predisposition to lower BMD. High-impact activities are particularly effective for bone accretion in children, including those with genetic risks for reduced BMD.
Area of Science:
- Pediatric Bone Health
- Genetics of Bone Metabolism
- Exercise Physiology
Background:
- Bone mineral density (BMD) is influenced by both genetic factors and physical activity (PA).
- The interplay between genetic predisposition and PA in childhood bone development remains unclear.
- Understanding these interactions is crucial for optimizing bone health strategies in children.
Purpose of the Study:
- To investigate whether physical activity (PA) modifies the effect of genetic variants associated with bone fragility on bone mineral density (BMD) in children.
- To determine if the benefits of PA on childhood bone accretion are dependent on genetic risk.
- To explore potential interactions between PA, genetic risk scores, and skeletal maturity (Tanner stage).
Main Methods:
- A cohort of 918 US children of European ancestry (aged 5-19 years) from the Bone Mineral Density in Childhood Study was analyzed.
- Physical activity (total, high-impact, low-impact) was assessed via questionnaire.
- A genetic score for BMD was calculated using GWAS-implicated variants, and bone Z-scores (femoral neck, total hip, spine, total body less head bone mineral content) were measured using DXA.
Main Results:
- A negative association was observed between the BMD genetic score and all measured bone Z-scores.
- Total PA, particularly high-impact PA, was positively associated with bone Z-scores, even in children with lower genetic predisposition.
- No significant interactions were found between PA, the overall BMD genetic score, and Tanner stage across skeletal sites.
- Exploratory analysis revealed a significant interaction between PA and a specific variant (rs2887571) in males, where PA increased bone mineral content in carriers of BMD-lowering alleles.
Conclusions:
- The positive effects of physical activity, especially high-impact activities, on bone development in children are robust and extend to those genetically predisposed to lower BMD.
- While overall genetic risk scores did not show interaction with PA, individual genetic variants may modulate the response to PA.
- Further research is needed to replicate the findings related to individual genetic variants and their interaction with PA in childhood bone accretion.
Abstract:
Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high-, and low-impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome-wide association study (GWAS)-implicated BMD variants. We used dual-energy X-ray absorptiometry to estimate femoral neck, total hip, and spine areal-BMD and total body less head (TBLH) bone mineral content (BMC) Z-scores. The BMD genetic score was negatively associated with each bone Z-score (eg, TBLH-BMC: estimate = -0.03, p = 1.3 × 10(-6) ). Total PA was positively associated with bone Z-scores; these associations were driven by time spent in high-impact PA (eg, TBLH-BMC: estimate = 0.05, p = 4.0 × 10(-10) ) and were observed even for children with lower than average bone Z-scores. We found no evidence of PA-adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA-genetic score-Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH-BMC in males (p interaction = 7.1 × 10(-5) ), where PA was associated with higher TBLH-BMC Z-score among the BMD-lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10(-9) ). In conclusion, the beneficial effect of PA on bone, especially high-impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS-implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.
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