OBJECTIVE: We hypothesized that bone mineral density increase following bisphosphonates treatments may be explained by the influence of the drug on the mechanical bone remodeling parameters. BACKGROUND: Patients treated with bisphosphonates continuously increase their bone mineral density. This increase is explained in the first 12-18 months following the treatment by the filling of the transient remodeling deficit. Recently, results of a clinical study of alendronate treatment over 7 years still show a continuous increase of bone mineral density. These results raised several questions regarding our understanding of bisphosphonates mode of action. METHODS: Bone remodeling is influenced by different factors including mechanical forces. In the present study, we propose then to consider the effect of bisphosphonates also under biomechanical considerations. RESULTS: Identification of the model with the clinical data showed that daily treatment of 10 and 20 mg alendronate decreased the bone turnover rate by 2% and 11%, respectively, in comparison with the 5 mg alendronate treatment. Moreover, the alendronate treatments decreases the resorption threshold stimulus by 19% (25%, 28%) for the 5 mg (10 and 20 mg, respectively) compared to placebo. CONCLUSIONS: The increase of bone mineral density following bisphosphonates treatment may then be explained by biomechanical considerations. Based on this description, bisphosphonates treatment may indeed change the susceptibility of bone to its biomechanical environment decreasing the mechanical threshold where bone should undergo resorption.