Accelerated bone resorption in senescence-accelerated mouse (SAM-P/6)

Age-associated changes in the femoral bone and in urine and serum composition were studied to understand the low bone mass in a substrain of senescence-accelerated mouse (SAM), SAM-P/6. Age-matched normal SAM-R/1 mice were used as controls. After 13 weeks of age, the concentration of hydroxyproline in the femur of SAM-P/6 was slightly but significantly lower. The urinary excretion rates of cAMP and calcium were higher in SAM-P/6 throughout the whole experimental period, and those of hydroxyproline and phosphorus were higher after 8 weeks. The serum concentrations of calcium and inorganic phosphorus of SAM-P/6 were higher at 13 and 20 weeks. At 5 weeks, the serum alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP) activities of SAM-P/6 were significantly higher. Furthermore, the serum of SAM-P/6 significantly stimulated calcium release from cultured fetal rat ulna. Since urinary cAMP and TRAP in the serum reflect the circulating level of parathyroid hormone and osteoclastic function, respectively, the present results suggest that, in SAM-P/6, accelerated bone resorption produced by a putative hyperparathyroid state causes the decrease in bone mass.