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Lecture

GDF5 significantly augments the bone formation induced by an injectable, PLGA-fiber reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia

Tuesday (09.05.2017)
12:20 - 12:40
Part of:


Introduction:

Biodegradable calcium phosphate cement (CPC) represents a therapeutic option for osteoporotic vertebral fractures. However, augmented local bone catabolism may require additional delivery of bone morphogenetic protein (BMP). Thus, a fiber reinforced, brushite-forming CPC with the BMP GDF5 was injected in sheep with lumbar osteopenia.

Methods:

Lumbar defects (diameter 5 mm) were place in old, osteopenic, female sheep (44 Merino sheep; 6 – 9 years; 68 - 110 kg) and treated with fiber-reinforced CPC alone (L4) or with CPC containing different dosages of GDF5 (L5; 1, 5, 100, and 500 µg; n = 5 or 6 each). The results were compared to those of untouched controls (L1). Three and 9 months post-operation, the effects of the CPC (± GDF5) were assessed ex vivo by measuring: i) bone mineral density (BMD); ii) bone structure, i.e., bone volume/total volume (assessed by micro-CT and histomorphometry), trabecular thickness, and trabecular number; iii) bone formation, i.e., osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralized surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; iv) bone resorption, i.e., eroded surface/bone surface; and v) compressive strength.

Results:

Compared to untouched controls (L1), both CPC (L4) and CPC+GDF5 (L5) numerically or significantly improved all parameters of bone formation, bone resorption, and bone structure at 3 and 9 months. Compared to CPC, additional significant effects of CPC+GDF5 were demonstrated for BMD and parameters of bone structure and formation (bone volume/total volume, trabecular thickness, and trabecular number; as well as mineralized surface/bone surface). The GDF5 effects were dose-dependent (predominantly in the 5 to 100 µg range) at 3 and/or 9 months.

Conclusion:

GDF5 significantly enhanced the bone formation induced by a PLGA-fiber reinforced CPC in sheep lumbar osteopenia, with a local dose as low as ≤ 100 µg GDF5 possibly sufficient to augment middle to long-term bone formation. The novel CPC+GDF5 combination may thus be an alternative to the bioinert, supraphysiologically stiff poly(methyl methacrylate) cement currently applied for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.

 

Speaker:
Prof. Dr. Raimund W. Kinne
Jena University Hospital
Additional Authors:
  • Dr. Matthias Bungartz
    Jena University Hospital, Germany
  • Dr. Elke Kunisch
    Jena University Hospital, Germany
  • Dr. Stefan Maenz
    Friedrich-Schiller-University Jena, Germany
  • Victoria Horbert
    Jena University Hospital, Germany
  • Dr. Long Xin
    Jena University Hospital, Germany
  • Francesca Gunnella
    Jena University Hospital, Germany
  • Dr. Joerg Mika
    University Hospital Giessen-Marburg, Campus Giessen
  • Juliane Borowski
    Jena University Hospital, Germany
  • Dr. Sabine Bischoff
    Jena University Hospital, Germany
  • Dr. Harald Schubert
    Jena University Hospital, Germany
  • Dr. Andre Sachse
    Jena University Hospital, Germany
  • Dr. Bernhard Illerhaus
    BAM Bundesanstalt für Materialforschung und –prüfung (BAM), Berlin
  • Prof. Dr. Jens Günster
    BAM Bundesanstalt für Materialforschung und –prüfung (BAM), Berlin
  • Dr. Joerg Bossert
    Friedrich-Schiller-University Jena, Germany
  • Prof. Dr. Klaus Jandt
    Friedrich-Schiller-University Jena, Germany
  • Dr. Frank Plöger
    BIOPHARM GmbH, Heidelberg
  • Dr. Olaf Brinkmann
    Jena University Hospital, Germany