A fragility fracture is associated with an increased risk of all-cause mortality, but its underlying factors are largely unidentified. We sought to test the hypothesis that low bone mineral density (BMD) is a risk factor for post-fracture mortality risk.
This prospective study involved 5,379 Caucasian men from the Osteoporotic Fractures in Men Study (MrOS) and 8,128 Caucasian women from the Study of Osteoporotic Fractures (SOF) with an average age of 74 years. The participants had had at least one femoral neck BMD measurement using DXA (Hologic QDR 1000 and QDR 2000). Fragility fractures were verified via medical records, and reported deaths were ascertained by a centralized review of death certificates. A multistate regression was conducted to quantify the simultaneous contribution of BMD to the risk of each correlated outcome (i.e., fragility fractures, deaths with no fracture, and post-fracture deaths), accounting for their complex interrelationships, competing risks and confounding effects of risk factors for fractures, lifestyle factors and comorbidities.
During a median follow-up of 12.3 years (IQR: 6.9-18.0) and 11.0 years (5.8-16.8),1,016 men and 2,731 women sustained a fragility fracture, respectively. There were 3,296 deaths (including 655 post-fracture deaths) in men and 4,835 deaths (1,644 post-fracture deaths) in women. Among individuals with no fracture, every standard deviation (SD) lower in BMD was independently associated with a 50%-60% increased risk of fragility fractures, but not associated with mortality risk (Figure). Importantly, low BMD at the time of fracture was independently associated with a 10%-20% increased risk of post-fracture mortality. The increased risk of post-fracture mortality was greater, albeit statistically non-significant, among osteoporotic, African- or Asian-American patients with a fragility fracture.
Our findings suggest that low BMD is a significant contributor to post-fracture excess mortality among patients with a fragility fracture, indicating potential additional survival benefits beyond bone health from osteoporosis treatment.