title: Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs.
abstract: The Göttingen minipig is one of the few large animal models that show glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of bone mineral density (BMD) and bone strength in minipigs can be recovered by treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were allocated to 4 groups when they were 30 months old: GC treatment for 8 months (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5 mg/kg body weight. IBN was administered intramuscularly and intermittently with an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and 15. Blood and urine samples were obtained every 2-3 months. After sacrificing the animals lumbar vertebrae L4 were tested mechanically (Young's modulus and ultimate stress). Histomorphometry was performed on L2 and mineral content determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean, p<0.001) during the first 8 months were more than recovered during the following 7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22% (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2) while deoxypyridinoline was comparable. This minipig study demonstrates that GC-induced impairment of bone strength can be effectively and consistently treated by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be monitored in vivo using QCT of the spine and by biochemical analyses, reflecting the changes in bone strength.
authors.affiliation: Medical Physics, Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany. glueer@rad.uni-kiel.de
authors.forename: C C
authors.initials: CC
authors.lastname: Glüer
authors.forename: K E
authors.initials: KE
authors.lastname: Scholz-Ahrens
authors.forename: A
authors.initials: A
authors.lastname: Helfenstein
authors.forename: G
authors.initials: G
authors.lastname: Delling
authors.forename: W
authors.initials: W
authors.lastname: Timm
authors.forename: Y
authors.initials: Y
authors.lastname: Açil
authors.forename: R
authors.initials: R
authors.lastname: Barkmann
authors.forename: J
authors.initials: J
authors.lastname: Hassenpflug
authors.forename: B
authors.initials: B
authors.lastname: Stampa
authors.forename: F
authors.initials: F
authors.lastname: Bauss
authors.forename: J
authors.initials: J
authors.lastname: Schrezenmeir
mesh_terms: D015502:Absorptiometry, Photon; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D000077557:Ibandronic Acid; D008159:Lumbar Vertebrae / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced* / Q000517:prevention & control*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005938:Glucocorticoids; D000469:Alkaline Phosphatase; D000077557:Ibandronic Acid