Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys

S. Y. Smith, Robert R. Recker, M. Hannan, R. Müller, F. Bauss

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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 μg/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 μg/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 μg/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 μg/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.

Original languageEnglish
Pages (from-to)45-55
Number of pages11
JournalBone
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2003

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Macaca fascicularis
Diphosphonates
Intravenous Administration
Bone and Bones
Bone Remodeling
Intravenous Injections
Femur Neck
Spine
Biomarkers
ibandronic acid
Densitometry
Metabolic Bone Diseases
Osteocalcin
Photon Absorptiometry
Therapeutics
Osteogenesis
Osteoporosis
Haplorhini
Alkaline Phosphatase
Estrogens

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hematology

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Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys. / Smith, S. Y.; Recker, Robert R.; Hannan, M.; Müller, R.; Bauss, F.

In: Bone, Vol. 32, No. 1, 01.01.2003, p. 45-55.

Research output: Contribution to journalArticle

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