Novel Risk Factors for Clinical Vertebral Fracture in Women

Abstract

Vertebral fracture (VF) is the most common type of fracture. Vertebral fractures are associated with significant disability, poorer quality of life, high cost, increased morbidity, higher mortality, and are predictive of future fracture risk. However, little is known about modifiable VF risk factors, which may be inherently different than for fractures at other sites due to different microarchitecture, biomechanics, and compressive loading. We therefore investigated the prospective association between several potential novel risk factors and risk of incident clinical vertebral fracture in women participating in the Nurses’ Health Study without a prior history of any fracture. The risk factors were: 1) diuretic use, including thiazides and loop diuretics; 2) proton pump inhibitors (PPI) and histamine-2-receptor antagonists (H2RA); and 3) body size, as measured by body mass index and waist circumference. Self-reported vertebral fracture was confirmed by medical record review. Cox proportional-hazards models were used to simultaneously adjust for potential confounders. We found that thiazide diuretics and loop diuretics are each independently associated with increased risk of vertebral fracture in women. We found that PPI use is independently associated with a modestly higher risk of VF and the risk increases with longer duration of use. There was no statistically significant association between H2RA use and VF risk. Larger waist circumference, a measure of central obesity, was independently associated with higher risk of VF in women. Greater lean body mass was independently associated with lower risk of VF in women. These findings suggest new potentially modifiable risk factors for clinical vertebral fracture, and underscore that risk factors for fractures are fracture site-specific.