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 investigated for its effects on bone quality in lumbar vertebrae in rats. Bone area, bone density and mechanical properties were assessed by peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA) and compression tests. Female and male groups of Wistar rats received either vehicle or 3, 7 or 15 mg/kg per day of ibandronate over 104 weeks orally by gavage. Compared with the control group, bone mineral density, compressive strength and stiffness were significantly higher in ibandronate-treated animals, whereas no changes occurred in strain or modulus of elasticity. The increase in vertebral body stress was significant in some of the ibandronate-treated groups. The changes in mechanical properties appear to be due 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 pQCT (r = 0.85) and maximal strength in vertebral bodies (p < 0.0001 each). In conclusion, we demonstrated that lifelong administration of doses of ibandronate far in excess of any therapeutically intended dose not only increases bone mass and apparent density, but also maintains or even slightly improves 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 after treatment with ibandronate.
Lalla
S
S
Department of Preclinical Research and Development, Bone Metabolism, Boehringer Mannheim GmbH, Germany.
Hothorn
L A
LA
Haag
N
N
Bader
R
R
Bauss
F
F
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077557:Ibandronic Acid; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013314:Stress, Mechanical
D004164:Diphosphonates; D000077557:Ibandronic Acid