Type Size
    ASBMR 2010 Annual Meeting

    PTH and ALN reduce fractures and alter bone mechanical properties in the oim/oim mouse model of OI

     Bone Acquisition and Pediatric Bone Disease (Clinical)
     Aging and Other Disorders of Bone and Mineral Metabolism (Clinical)

    Poster Sessions, Presentation Number: FR0445
    Session: Welcome Reception and Plenary Poster Session
    Friday, October 15, 2010 5:45 PM - 7:00 PM, Metro Toronto Convention Centre, South Building, South Building: Hall E

    Poster Sessions, Presentation Number: SA0445
    Session: Poster Session I and Poster Tours
    Saturday, October 16, 2010 11:30 AM - 1:30 PM, Metro Toronto Convention Centre, South Building, South Building: Hall E

    * Cesare Ciani, Hospital for Special Surgery, USA, Kirsten Stoner, Cornell University, USA, Michael Cross, Hospital for Special Surgery, USA, Liza Osagie, Hospital for Special Surgery, USA, Bettina Willie, Hospital for Special Surgery, USA, Marjolein Van Der Meulen, Cornell University, USA, Mathias Bostrom, Hospital for Special Surgery, USA

    Osteogenesis Imperfecta (OI), a genetic disorder typically caused by a mutation in Type I collagen, manifests with defective connective tissue resulting in multiple skeletal fractures. Intermittent bisphosphonate therapy is the standard treatment, while parathyroid hormone (PTH) is currently under evaluation as an alternative. This study investigated the effects of PTH, both individually and in combination with alendronate (ALN) in the oim/oim mouse model of OI.
    68 oim/oim mice and 68 wild type (WT) mice were randomized into 4groups: saline, ALN, PTH and PTH+ALN, each for 12weeks. A baseline untreated OI group was euthanized at 4weeks (Table 1). Outcome measurements included fracture incidence, cancellous histomorphometry and three-point bend testing.
    Fracture number was reduced in all OI treated groups compared to the OI saline group (p<0.05), with ALN causing the greatest reduction (2.5 compared to 5.4 of the saline group), and PTH+ALN the least (Figure 1). ALN increased trabecular number in both OI and WT mice (9.1 and 9.4 respectively compared to 2.9 and 4.8 in OI and WT saline groups). ALN and ALN+PTH significantly increased bone volume fraction (BV/TV) in OI mice compared to OI PTH group, resulting in BV/TV values equal to untreated WT levels (Figure 2). PTH did not alter any cancellous histomorphometry. ALN decreased energy to failure and increased bending stiffness in all groups. In OI mice PTH+ALN restored strength and energy to failure to WT saline levels. ALN and PTH+ALN treatments increased bending strength in OI mice.
    While PTH alone did not alter cancellous histomorphometry, fracture incidence was reduced comparable to ALN treatment. PTH+ALN improved cancellous architecture and reduced fracture number. Reduction in fracture number can be attributed to increased bone volume fraction when OI bone was treated with ALN. Individual ALN treatment produced brittle behavior in both OI and WT femora, but used in combination with PTH strength and ductility were rescued to WT levels. Ultimately, PTH and ALN’s effect on fracture number, and their synergistic effect on mechanical properties cannot solely be ascribed to morphological changes, but reflects changes in intrinsic bone tissue material properties to be assessed in future studies.

    Disclosures: None

    * Presenting Authors(s): Cesare Ciani, Hospital for Special Surgery, USA