Male rodent model of age-related bone loss in men

Osteoporosis is a common occurrence in aging men. There is currently no app ropriate animal model for studying age-related bone loss in men. To determi ne whether male Sprague-Dawley (SD) rats experience bone loss with aging an d whether this rodent model is appropriate for studying age-related bone lo ss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the left proximal tibia using peripheral quantitativ e computed tomography (pQCT) densitometry. In the L-4 vertebra of the male SD rats, cortical bone mineral content (BMC), cortical bone mineral density (BMD), and cortical bone thickness (Ct.Th) increased to a maximum at about 4 months of age and then plateaued. Vertebral cortical BMC began to decrea se after about 13 months and vertebral Ct.Th began to decrease after about 9 months. By 27 months of age, vertebral cortical BMC decreased by 26.1% (p < 0.0001) and vertebral Ct.Th decreased by 31% (p < 0.0001). Vertebral can cellous BMC and vertebral cancellous BMD increased to a maximum at about 3 months of age and then declined progressively with aging after a short plat eau. From 3 to 27 months of age, vertebral cancellous BMC and vertebral can cellous BMD had decreased linearly by 35.4% (p < 0.0001) and 49.4% (p < 0.0 001), respectively. Both vertebral periosteal and vertebral endocortical pe rimeters of the L-4 vertebra of the rats increased with aging. From 9 to 27 months of age, the percent increase of vertebral endocortical perimeter (1 9.8%, p < 0.0001) was higher than that of vertebral periosteal perimeter (7 .4%,p < 0.0001). This process was associated with a decrease with aging in vertebral Ct.Th. In addition, cancellous bone in the femoral neck and the p roximal tibia began to be lost at 9 months of age and, by 27 months of age, cancellous BMC and cancellous BMD decreased by 59.7% (p < 0.0001) and 58.4 % (p < 0.0001), respectively, in the femoral neck and by 72.2% (p < 0.0001) and 71.4% (p < 0.0001), respectively, in the proximal tibia. To gain furth er insight into the effects of aging on cancellous bone in the L-4 vertebra , histomorphometry was done on the L-4 vertebral body of animals aged 3, 6, 9, 18, and 24 months after pQCT densitometry. From 3 months of age and the reafter, cancellous bone volume (BV/TV) decreased progressively and, by 24 months, there was a decrease of 35.7% (p < 0.0001). In the L-4 vertebra, si ngle- and double-labeled surfaces, mineral apposition rate (MAR), and bone formation rate (BFR/BS) decreased with aging. In conclusion, age-related bo ne loss in male SD rats started mostly from 9 months of age when bone growt h had been completed. Aging male SD rats experience bone loss comparable to that seen in men. Thus, male SD rats represent an appropriate animal model of age-related bone loss in men. We recommend using male SD rats that are 9 months old as the starting age for age-related bone loss. We also suggest using the L-4 vertebra and femoral neck as the clinically relevant bone si tes for determining the cause of the loss of bone, and how and whether ther apeutic agents could modulate age-related bone loss in men. (C) 2001 by Els evier Science Inc. All rights reserved.