Spontaneous osteoclastogenesis: Hypothesis for gender-unrelated osteoporosis screening and diagnosis

Women are at greater risk of developing osteoporosis (OP). However, in the past few years it has become more widely recognized that OP is a significant problem also in men although OP is frequently under-diagnosed and, consequently, under treated in men. Most guidelines, screening and fracture risk evaluation methods as well as pharmacologic agents have been developed for women and then adapted to men. Bone Mineral Density (BMD) measurement by Dual X-ray Absorptiometry (DEXA) is reported as T score and the capability of DEXA to diagnose OP and predict fracture risk is still debated. In addition, the use of female T score references for the diagnosis of OP in men is incorrect for the following reasons: 1) DXA definition was developed just for Caucasian women, 2) men and women display structural differences in terms of bone growth, catabolism and size; 3) aging men have more periosteal apposition, less cortical porosity and endocortical resorption than aging women; and 4) T scores results, both in man and in women, can be affected by the presence of co-morbidities and it is known that in men OP is often secondary. From a biological point of view, OP is mainly due to increased osteoclastic activity leading to an imbalance in bone remodeling that favors resorption. However, some evidence suggests a more complex identity for osteoclasts (OCs) over and above their simple role of 'bone eaters'. In our laboratory, we observed spontaneous OCs formation in vitro in peripheral blood mononuclear cells (PBMC) from OP patients (n.12 female patients and n.6 male patients; DXA T score-2.5 or less). Some researchers demonstrated OCs gender differences in bone resorption activity of female-derived versus male-derived OCs. Indeed, further data from our laboratory also showed gender differences in number of spontaneously differentiated OCs and differentiation time. Therefore, we hypothesized that it would be possible to perform OP screening and diagnosis observing and measuring PBMCs different ability to differentiate spontaneously into OCs in male and female patients. If this hypothesis will be confirmed, it will result in an effective and efficient strategy for OP screening, diagnosis, monitoring and fracture prevention, targeting health service resources on selected patients. However, our hypothesis must be tested in a properly designed clinical trial and several key issues still need to be addressed.