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 < 0.001) in women and -0.030 (95% CI, -0.042 to -0.018; p < 0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both men and women.
Subject(s)
Body Mass Index , Bone Density , Femoral Neck Fractures , Aged , Aged, 80 and over , Female , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/immunology , Femoral Neck Fractures/metabolism , Femoral Neck Fractures/physiopathology , Humans , Male , Middle Aged , Prospective Studies , Radiography , Risk Factors , Sex FactorsABSTRACT
Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women.
