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.
1Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street, Suite 507, Chicago, IL 60612. E-mail address for A.S. Virdi: firstname.lastname@example.org
2Department of Periodontology, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
3Metabolic Disorders, Amgen, Inc., One Amgen Center Drive, 29-1-A, Thousand Oaks, CA 91320
4Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, LA 70803