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Causal inference of the effect of adiposity on bone mineral density in adults.
MedLine Citation:
PMID:  23045999     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: The causal effect of adipose tissue on bone mass and the direction of its net influence have not been directly assessed in adult humans. Using the Mendelian randomization analysis, we assessed the causality of adiposity in measurements of bone mass in adult males and females. DESIGN AND METHODS: Subjects consisted of 2,154 adults aged 25-54 years from a cross-sectional cohort of the employees of the Electricity Generating Authority of Thailand. Body composition was determined after at least 3 h of fasting using multi-frequency bioelectrical impedance analysis. Bone mineral density was assessed by dual energy X-ray absorptiometry. A polymorphism in the fat mass and obesity-associated gene (FTO rs9939609) was used as an instrument in the Mendelian randomization analysis. RESULTS: The genotype distribution of the FTO rs9939609 polymorphism was 61.1% TT, 33.9% AT and 5.0% AA. The average body mass index (BMI), body fat mass and percent body fat were 23.9 kg/m(2) (SD = 3.6), 17.9 kg (SD = 6.6) and 26.8% (SD = 7.2), respectively. The FTO rs9939609 polymorphism was significantly correlated with BMI (coefficient = 0.673 kg/m(2) , P < 0.001), body fat mass (coefficient = 0.948 kg, P < 0.001) and percent body fat (coefficient = 0.759%, P < 0.01). An instrumental variable (IV) regression model, using BMI as the intermediate phenotype, suggested that FTO was a strong IV. Also, the FTO-BMI polymorphism was significantly associated with total hip and femoral neck bone mineral density (BMDs) but was not correlated with total spine BMD, with estimated correlation coefficients of 0.0189 (95% CI: 0.0046, 0.0332), 0.0149 (95% CI: 0.0030, 0.0268) and 0.0025 (95% CI: -0.0131, 0.0136) g/cm(2) , respectively. The variances of BMDs explained by the FTO-BMI were 19.0%, 21.3%, and 1.1%, respectively. Similar trends were also observed for the FTO-body fat mass and FTO-percent body fat correlations. CONCLUSIONS: Mendelian randomization analysis suggests that adiposity might be causally related to bone mineral density at the femur but not at the spine. © 2012 Blackwell Publishing Ltd.
Authors:
Daruneewan Warodomwichit; Chanika Sritara; Ammarin Thakkinstian; La-Or Chailurkit; Sukit Yamwong; Wipa Ratanachaiwong; Boonsong Ongphiphadhanakul; Piyamitr Sritara
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  Clinical endocrinology     Volume:  -     ISSN:  1365-2265     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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