A pre-existing osteoporotic fracture, in combination with low bone mass, together form a much stronger predictor of the risk of vertebral fracture than low bone mass, or fracture alone. The very high power of this combination to predict additional fractures suggests: 1) that any factor equivalent to a """"""""first fracture"""""""" will be of great value in the prediction of a patient's fracture risk, and 2) that a systemic bone """"""""quality"""""""" issue may be involved in the etiology of some osteoporoses. Microcracks in vertebral cancellous hard tissue may measure a patient's risk of a first fracture. The reasoning is: a) the primary damage mechanism in vertebral cancellous bone is microcracks, b) significant numbers of natural microcracks have been found in human vertebral cancellous bone, c) microcracks are normally observed by engineers prior to material fracture, and therefore, d) microcracks in vertebral bone probably foreshadow fracture (microcracks are, after all, small bone fractures). In this application, therefore, using microcrack density as an indicator, new predictors for fracture risk will be developed. Preliminary data indicate that microcracks accumulate in vertebral tissue which: 1) contains more collagen by weight, 2) has a greater mean tissue age (independent of patient chronological age), and 3) has low bone volume fraction. Preliminary data also show that cancellous bone strength is negatively correlated with naturally occurring microcrack density (r=-0.63), suggesting that bone quality is degraded by microcracks. Very recent (March 3, 1996) preliminary data indicate that cancellous specimens can be a priori segregated into two statistically distinct quality groups using a finite element-based method. Segregation into these groups increases the r2 of bone apparent strength predicted by bone volume fraction by more than 12%. High quality specimens do not accumulate high densities of microcracks. Low quality specimens can accumulate many microcracks in the presence of high body weight. The variable best separating high and low quality bone was average trabecular hard tissue stiffness. Interindividual variance in hard tissue properties may explain variance which remains after bone strength is predicted by bone density. As a consequence, the applicant suggests that methods which: a) predict which patients are at risk for accumulating microcracks (i.e., the conditions conducive to a first fracture), and b) determine the effect of naturally accumulated microcracks on cancellous bone, should provide tools for better prediction of fracture risk.
