Response to questions regarding conclusions reached in “Age dependence of femoral strength in white women and men” (2010)

We thank the Editors for the opportunity to assess Dr. Kaufman's analysis of our data and to further expound on the clinical relevance of our findings. Dr. Kaufman is concerned that our analysis implicitly assumes that “femoral strength as estimated by BCT is a much better quantity to estimate fracture risk than is aBMD.” He also concludes that “the implication that BCT provides superior information on bone strength and fracture risk at the proximal femur to that provided by aBMD is questionable at least based on the data provided in the article by Keaveny and colleagues.” In fact, our analysis does not address assessment of fracture risk, nor does it assume that our BCT-derived estimates of femoral strength are better at fracture risk assessment than aBMD. We were careful in our conclusions not to broach comparatives of fracture risk assessment because we had no fracture outcome data available for this cohort at the time of our analysis. Instead, the focus of this article was on the more general issue of age-related trends for the population, highlighting differences in trends for aBMD and femoral strength, and not addressing superiority of one over the other. As such, Dr. Kaufman mischaracterized our study. In reaching his conclusions, Dr. Kaufman made several unsubstantiated statements. For example, he concluded from analysis of our data that aBMD of the femoral neck is “an excellent proxy for femoral strength.” Dr. Kaufman's argument was based on the relation between age-specific mean values between the two variables. His reported correlation was so high because, after midlife, we found that mean strength and mean aBMD both declined in an approximately linear fashion with age. By Dr. Kaufman's logic, age also would be an excellent proxy for aBMD. However, none of this speaks to the correlation for individuals, which is the relevant issue for fracture risk assessment. In a study of clinically defined postmenopausal osteoporotic women, for example, the correlation between BCT-derived strength and dual-energy X-ray absorptiometry (DXA)–derived aBMD was quite low (R2 ≈ 0.50).1 Dr. Kaufman mischaracterized our second conclusion by extrapolating his paraphrasing to comparisons of fracture risk assessment—but, in fact, we made no conclusions about fracture risk assessment or the superiority of BCT-derived femoral strength over aBMD in this regard. Dr. Kaufman's also dismissed our 3000 N cut point for femoral strength as “largely arbitrary.” Since this empirical cut point was based on prospective, fracture outcome clinical data (albeit for men),2 clearly it was not chosen arbitrarily. Mathematically, of course, one can increase the T-score cut point to match the prevalence for the strength cut point. But this has little relevance in a clinical context because increasing the T-score will compromise specificity, which is not desirable clinically, and changing the World Health Organization aBMD criteria for the definition of osteoporosis is not feasible. Dr. Kaufman also questioned the relevance of our results, stating that our observation of greater changes in strength than aBMD “is of little consequence.” While this viewpoint may be reasonable from a purely mathematical perspective, the clinical implications are more nuanced. aBMD is used widely as an implicit surrogate for bone strength. In this clinical context, our results raise the issue of whether such widespread reliance on aBMD as a surrogate for bone strength may provide a misleading clinical impression that annual percent reductions in femoral strength are on the same order as in aBMD—about 0.5% to 0.7% per year (see Fig. 4 of our paper). Such a rate of loss does not appear too alarming, does not change much with aging, and probably would justify the current approach of waiting until individuals are at very high risk before commencing treatment. However, our results suggest instead that the rate of loss in strength is much greater, particularly in elderly women. This raises the possibility that too few women are being treated and too late. Thus, while our results are indeed consistent with current efforts to improve clinical fracture risk assessment, we believe that they additionally provide unique insight into effects of age on femoral strength and highlight issues central to the debate of how one might improve management of osteoporosis from a public health perspective.