THE EFFECTS OF 2-YEAR TREATMENT WITH THE AMINOBISPHOSPHONATE ALENDRONATE ON BONE METABOLISM, BONE HISTOMORPHOMETRY, AND BONE STRENGTH IN OVARIECTOMIZED NONHUMAN-PRIMATES

This study examined the effect of 2 yr of treatment with the aminobisp hosphonate alendronate (ALN) (0.05 or 0.25 mg/kg i.v. ALN every 2 wk) on estrogen deficiency bone loss and bone strength changes in ovariect omized (OVX) baboons (n = 7 per group) and the ALN mode of action at t he tissue level. Biochemical markers of bone turnover increased in OVX animals and were maintained by ALN treatment at non-OVX levels (low d ose) or below (high dose). 2 yr of treatment produced no cumulative ef fects on bone turnover markers. Histomorphometry showed a marked incre ase in cancellous bone remodeling in OVX animals. Activation frequency increased from 0.48 to 0.86 per yr (L5 vertebra), and the osteoid sur faces from 9 to 13.5% (P < 0.05). No changes were observed in eroded a nd osteoclast surfaces. ALN treatment decreased activation frequency a nd indices of bone formation to control levels (low dose) or below (hi gh dose), did not change indices of mineralization, and increased bone mineral density (BMD) in the lumbar vertebrae (L2-L4) by 15% at 0.25 mg/kg (P < 0.05), relative to vehicle-treated animals. The mean streng th of cancellous bone (LA) increased by 44% (low ALN dose) and 100% (h igh dose), compared with vehicle. The strength of individual bones cor related with the square of the L2-LA BMD (r = 0.91, P < 0.0034). In co nclusion, ALN treatment reversed the effects of ovariectomy on cancell ous bone turnover and increased bone mass and bone strength in baboons .