Bone densitometry and true BMD accuracy for predicting fractures: what are the alternatives?

Osteoporosis & bone fragility Every second woman and every fifth man aged 50 years or over sustains a fragility fracture (vertebral, hip, wrist or proximal humerus facture) during the rest of their lifetime [1]. Fractures virtually always lead to temporary morbidity, and with age, the likelihood of permanent and more severe comorbidities markedly increases [2]. For example, of those who sustain a hip fracture, the majority will never reach the same level of physical functioning that they had prior to the fracture; many of those who lived earlier at home will become institutionalized, and one fifth will die during the first year after the fracture [3]. While the present situation readily forms a considerable public health problem, the burden of fragility fractures to our societies is predicted to increase as larger proportions of the population will reach very old and frailty age [4]. Efficient preventive measures to cut this trend are urgently needed. Cost-effective prevention of any health problem rests on reliable case-finding of individuals who are at high risk to warrant a properly targeted intervention (e.g., preventive lifestyle actions or medical treatment) and those likely to benefit from these measures. The backbone of case-finding is a method that provides a valid (i.e., accurate and clinically meaningful) and consistent (i.e., precise) measurement of the health condition of interest in the given individual. As regards to osteoporosis and related bone fragility, in 1994 the WHO proclaimed the dual-energy x-ray absorptiometry (DXA) the method, and the areal bone mineral density (BMD) the primary measurement of bone status [5]. The operational definition of osteoporosis was set at 2.5 standard deviations (SD) below the young adult mean BMD level expressed as T-score of -2.5 or less. The diagnostic T-score threshold identifies approximately 30% of the postmenopausal female population as having osteoporosis either at the spine, hip or forearm [6]. Interestingly, the same percentage also equals to the lifetime risk of fractures at those sites [6]. The similarity between these two independent numbers may allure one to conclude that they are synonymous. If so, osteoporosis, as defined by low areal BMD, would be the major underlying factor of fragility fractures and the DXA-measured Requirements for clinical densitometric evaluation of fracture risk of an individual patient are obvious: the method must be noninvasive and safe, it should provide adequate assessment of bone fragility, be sensitive and specific enough to detect small differences or changes in structural bone traits that are vital to bone strength, and appreciably add to the predictive ability of prior assessment of fracture risk based on established clinical risk factors of the given patient. At present, clinical evaluation of bone fragility largely rests on dual-energy x-ray absorptiometry (DXA) and the obtained areal bone mineral density (BMD) and the Tand Z-scores derived from it. Whereas BMD correlates strongly with bone strength and low BMD indicates increased relative risk of fragility fractures, the overall proportion of fractures attributable to osteoporosis, as diagnosed by low DXA-measured BMD, remains quite modest. This paradox apparently arises from the limited ability of areal BMD to elicit individual patient’s bone strength and from too narrow an insight to multiple factors that truly contribute to fractures. Clinical assessment of patient-specific bone fragility and fracture prediction should rely on comprehensive assessment of individual clinical risk factors accounting for both bone fragility and falling. Regarding the former, it is noteworthy that bone traits derived from 3D bone images have not alone improved the prediction of bone strength compared with BMD, but the combination of independent bone traits seems to do so. This being the case, the biomechanical finite element ana lysis of 3D bone model holds an excellent promise to yield more meaningful information on individual bone fragility and susceptibility to fractures.