Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats

As part of a long-term safety study the bisphosphonate ibandronate was inve stigated for its effects on bone quality in lumbar vertebrae in rats. Bone area, bone density and mechanical properties were assessed by peripheral qu antitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DX A) and compression tests. Female and male groups of Wistar rats received ei ther vehicle or 3, 7 or 15 mg/kg per day of ibandronate over 104 weeks oral ly by gavage. Compared with the control group, bone mineral density, compre ssive strength and stiffness were significantly higher in ibandronate-treat ed animals, whereas no changes occurred in strain or modulus of elasticity. The increase in vertebral body stress was significant in some of the iband ronate-treated groups. The changes in mechanical properties appear to be du e mainly to an increase in bone mass. A highly significant correlation was found between bone mineral density measured either by DXA (r = 0.86) or pQC T (r = 0.85) and maximal strength in vertebral bodies (p<0.0001 each). In c onclusion, we demonstrated that lifelong administration of doses of ibandro nate far in excess of any therapeutically intended dose not only increases bone mass and apparent density, but also maintains or even slightly improve s bone quality. Bone mineral density measured either by pQCT or DXA can be used as a predictor for ultimate strength in rat lumbar vertebral bodies af ter treatment with ibandronate.