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Sclerostin Antibody Treatment Improves Implant Fixation in a Model of Severe Osteoporosis

Virdi, Amarjit S. PhD; Irish, John MD; Sena, Kotaro DDS, PhD; Liu, Min PhD; Ke, Hua Zhu MD; McNulty, Margaret A. PhD; Sumner, Dale R. PhD

Journal of Bone & Joint Surgery - American Volume: 21 January 2015 - Volume 97 - Issue 2 - p 133–140
doi: 10.2106/JBJS.N.00654
Scientific Articles
Supplementary Content

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:

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

Copyright 2015 by The Journal of Bone and Joint Surgery, Incorporated
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