Relationship Between Body Mass Index and Fracture Risk Is Mediated by Bone Mineral Density

ABSTRACT The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator....

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Bibliographic Details
Published in:Journal of bone and mineral research 2014-11, Vol.29 (11), p.2327-2335
Main Authors: Chan, Mei Y, Frost, Steve A, Center, Jacqueline R, Eisman, John A, Nguyen, Tuan V
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
BMD
BMI
Body Mass Index
Bone Density
Female
Femoral Neck Fractures - diagnostic imaging
Femoral Neck Fractures - immunology
Femoral Neck Fractures - metabolism
Femoral Neck Fractures - physiopathology
FRACTURE
Fractures
Humans
Male
MEDIATION ANALYSIS
Men
Middle Aged
MULTICOLLINEARITY
OBESITY
Older people
Osteoporosis
Prospective Studies
Radiography
Risk Factors
Sex Factors
Women
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Summary:ABSTRACT The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual‐energy X‐ray absorptiometry (DXA; GE‐LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X‐ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI‐fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD‐adjusted results (variance inflation factor [VIF] = 1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were −0.048 (95% CI, −0.059 to −0.036; p 
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.2288