Sclerostin antibody treatment improves implant fixation in a model of severe osteoporosis

J Bone Joint Surg Am. 2015 Jan 21;97(2):133-40. doi: 10.2106/JBJS.N.00654.

Abstract

Background: The mechanical fixation of orthopaedic and dental implants is compromised by diminished bone volume, such as with osteoporosis. Systemic administration of sclerostin antibody (Scl-Ab) has been shown to enhance implant fixation in normal animals. In the present study, we tested whether Scl-Ab can improve implant fixation in established osteoporosis in a rat model.

Methods: We used an ovariectomized (ovx) rat model, in which we found a 78% decrease in trabecular bone volume at the time of implant surgery; sham-ovx, age-matched rats were used as controls. After placement of a titanium implant in the medullary cavity of the distal aspect of the femur, the rats were maintained for four, eight, or twelve weeks and treated biweekly with Scl-Ab or with the delivery vehicle alone. Outcomes were measured with use of microcomputed tomography, mechanical testing, and static and dynamic histomorphometry.

Results: Scl-Ab treatment doubled implant fixation strength in both the sham-ovx and ovx groups, although the enhancement was delayed in the ovx group. Scl-Ab treatment also enhanced bone-implant contact; increased peri-implant trabecular thickness and volume; and increased cortical thickness. These structural changes were associated with an approximately five to sevenfold increase in the bone-formation rate and a >50% depression in the eroded surface following Scl-Ab treatment. Trabecular bone thickness and bone-implant contact accounted for two-thirds of the variance in fixation strength.

Conclusions: In this model of severe osteoporosis, Scl-Ab treatment enhanced implant fixation by stimulating bone formation and suppressing bone resorption, leading to enhanced bone-implant contact and improved trabecular bone volume and architecture.

Clinical relevance: Systemic administration of anti-sclerostin antibodies might be a useful strategy in total joint replacement when bone mass is deficient.

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Morphogenetic Proteins / immunology
  • Bone Resorption / etiology
  • Bone Resorption / prevention & control
  • Disease Models, Animal
  • Female
  • Genetic Markers / immunology
  • Osseointegration / drug effects*
  • Osteogenesis / drug effects
  • Osteoporosis / complications*
  • Ovariectomy
  • Prosthesis Failure / drug effects*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antibodies
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • Sost protein, rat