title: Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys.
abstract: Using a clinically relevant regimen, this study investigated the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, biochemical markers of bone turnover, densitometry, histomorphometry, biomechanical properties, and bone concentration in aged ovariectomized monkeys. Sixty-six female cynomolgus monkeys, aged 9 years and older, were ovariectomized (OVX) or sham operated. Intravenous (iv) bolus injections of ibandronate at 10, 30, or 150 microg/kg or placebo were administered at 30-day intervals (corresponding to intervals of 3 months in humans), starting at OVX, for 16 months. OVX significantly decreased bone mass at the lumbar spine, proximal femur, femoral neck, and radius and increased bone turnover in a time-dependent manner, as assessed by dual energy X-ray absorptiometry, peripheral quantitative computed tomography, or histomorphometry. Ibandronate iv bolus injections administered at 30 microg/kg every 30 days prevented osteopenia induced by estrogen depletion. OVX-induced increases in bone turnover (as determined by activation frequency, bone formation rate, and biochemical markers of bone turnover, including urinary N-telopeptide and deoxypyridinoline excretion and serum values for osteocalcin and bone-specific alkaline phosphatase) were suppressed on treatment, and bone mass, architecture, and strength were preserved at clinically relevant sites. Treatment with high-dose (150 microg/kg/dose) iv bolus injections of ibandronate further increased bone mass and improved bone strength at both the spine and femoral neck, without adversely affecting bone quality. In contrast, treatment with a 10 microg/kg/dose only partially prevented the OVX-induced effects. These data support the potential for the long-term administration of ibandronate by intermittent iv bolus injections in humans to prevent osteoporosis and improve bone quality at clinically relevant sites.
authors.affiliation: ClinTrials BioResearch Ltd., 87 Senneville Road, Senneville, Quebec, Canada H9X 3R3.
authors.forename: S Y
authors.initials: SY
authors.lastname: Smith
authors.forename: R R
authors.initials: RR
authors.lastname: Recker
authors.forename: M
authors.initials: M
authors.lastname: Hannan
authors.forename: R
authors.initials: R
authors.lastname: Müller
authors.forename: F
authors.initials: F
authors.lastname: Bauss
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000378:metabolism / Q000517:prevention & control*; D004164:Diphosphonates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D010052:Ovariectomy / Q000706:statistics & numerical data
chemical_list: D004164:Diphosphonates; D000077557:Ibandronic Acid