Purposes: The purpose of the current project is to investigate the roles of osteocalcin-insulin reaction loop in modeling adult skeleton under conditions of dietary manipulations and endurance exercise training. Methods：Adult male Sprague Dawley rats (age: 6 month) were body weight matched and assigned to one of the six groups, which were 1) the CON group: fed ad libitum control group; 2) the EE group, animals were subjected to a 9-week treadmill endurance running training regime; 3) the CR group, animals were fed under 40% caloric restriction. In addition, another similar three groups, which were the 4) CON+ZOL, 5) EE+ZOL and 6) CR+ZOL groups were treated with bisphosphonate (zoledronic acid, dose: 100mg/kg b.w.). Bisphosphonate was used as a functional mediator in purpose of down-regulate osteocalcin level. Static histomorphometry, densitometry and serum assays were conducted for the current study. Two-way ANOVA was used for data analyses. Results：After the 9-week experimental periods, the CR, CR+ZOL, EE and EE+ZOL groups revealed significantly lower body weight gain (p<0.05). In zoledronic acid treated groups, various densitometric and histomorphometric measurements demonstrated a higher bone mineral accumulation (p<0.05). In serum markers, exercise and caloric restriction showed main effects for enhancing insulin sensitivity (p<0.05). And, groups treated with bisphosphonate showed higher serum insulin levels in baseline (p<0.05), but not in time points after glucose loading. Zoledronic acid treatment showed main effects in down regulating serum levels of carboxylated (OC) and undercarboxylated (unOC) (p<0.05). In addition, CR groups revealed lower serum OC and unOC. Interestingly, exercise reversed the down-regulation of OC and unOC caused by zoledronic acid (p<0.05). Conclusions：By using bisphosphonate as a functional inhibitor, insulin sensitivity was not blunt, suggesting osteocalcin might not directly involved in glucose regulation. Nevertheless exercise can be an antagonist to counteract bisphosphonate caused quietness on bone metabolism.