The Importance and Possible Clinical Impact of Measuring Trabecular and Cortical Bone Microstructure to Improve Fracture Risk Prediction

[Extract] Osteoporosis is characterized by reduced bone strength caused by microstructural deterioration of the trabecular bone, increase in cortical porosity, and cortical thinning.1 Neither of these microstructural changes can be specifically assessed using dual‐energy X‐ray absorptiometry (DXA) commonly used and recommended to diagnose osteoporosis and bone fragility. However, the relationship between DXA‐derived areal bone mineral density (BMD) at the hip and risk of fracture has been well established. Every standard deviation decrease in BMD increases the risk of incident hip fracture by nearly three times.2 Fracture risk is not only dependent on bone fragility but also on general frailty, which becomes more prevalent with aging, poor balance, and other factors intricately connected to increased risk of falls.3 Incorporation of falls history and measures of physical function and muscle mass are most likely necessary to improve fracture risk prediction by capturing the falls risk dimension of fracture etiology. Because fracture risk also depends on clinical risk factors, of which some are independent of BMD, the use of risk calculators, such as FRAX, incorporating clinical risk factors, has been shown to improve the sensitivity to identify patients with incident fractures.4 As a result, many guidelines consider both BMD and fracture risk when proposing intervention thresholds.5 Using only the osteoporosis diagnosis6 to predict fractures has poor sensitivity and the majority of patients having fractures do not have osteoporosis.7 Therefore, much can be gained by attempting to account for clinical risk factors, falls risk, and developing enhanced methods to characterize skeletal fragility in order to improve the ability to detect risk patients before they fracture. Recently, results from a large meta‐analysis of prospective studies of women and men who had their bones measured with high‐resolution peripheral computed tomography (HRpQCT) identified several bone microstructural traits, including failure load and trabecular volumetric BMD, associated with incident fracture, although the HRpQCT indices only increased the area under the curve slightly in addition to femoral neck BMD and clinical risk factors