Unlabelled: The relationship between bone mineral density (BMD) at the femoral neck and fracture risk was determined in a meta-analysis of primary data of 307205 men and women from 53 cohort studies. Low BMD was an important predictor of fracture risk, particularly for hip fracture.

Introduction: This study aimed to quantify the relationship between DXA-measured femoral neck BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value on fracture risk, with a view to updating FRAX®.

Methods: We studied 307,205 men and women from within 53 predominately population-based cohorts followed up for an average of 8.7 years and a total of 2,683,185 person-years. The association of BMD and fracture risk was examined using a Poisson model in each cohort separately by sex. Results were expressed as a gradient of risk (GR, hazard ratio/standard deviation decrease in BMD). The different studies were then merged using weighted coefficients. RESULTS: Most hip fractures arose in men and women with low bone mass or osteoporosis at baseline (73% and 92%, respectively) as was also the case for MOF (65% and 85%, respectively). BMD at the femoral neck strongly predicted hip fractures both in men and women with a similar gradient of risk and absolute risk at any given T-score. At the age of 65 years, the GR was 2.73 (95% CI = 2.29-3.26) in men and 2.61 (95% CI = 2.34-2.92) in women. However, the magnitude of association was significantly dependent on age, with a higher gradient of risk at younger ages. For example, at age 50 years, the GR was 3.49 (95% CI 2.51-4.84) in men and decreased to 2.14 (1.96-2.34) at age 80 years. The change in GR with age was slightly less marked in women (3.23 [2.75-3.80] and 2.11 [1.99-2.44], respectively). The GR for major osteoporotic fracture (MOF) remained unchanged with age (p = 0.12 for women and p = 0.89 for men). A significant decrease in GR for hip fracture was observed with increasing duration of follow-up, but the magnitude of the effect was modest compared with the effect of age. For other fracture outcomes, including non-hip major osteoporotic fracture, the gradient of risk was lower than for hip fracture.

Conclusions: Femoral neck BMD is a risk factor for fracture of substantial importance, particularly for future hip fracture. The lower magnitude of association at older age is consistent with other non-skeletal factors contributing to hip fracture risk with advancing age. Its validation on an international basis supports its use in case finding strategies. Its use should, however, take account of the variations in predictive value of BMD with age, sex, length of follow-up, and BMD.