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

• Published in: Journal of bone and joint surgery. American volume Vol. 97; no. 2; pp. 133 - 140
• Main Authors: Virdi, Amarjit S, Irish, John, Sena, Kotaro, Liu, Min, Ke, Hua Zhu, McNulty, Margaret A, Sumner, Dale R
• Format: Journal Article
• Language: English
• Published: United States Copyright by The Journal of Bone and Joint Surgery, Incorporated 21-01-2015
• Subjects: 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
• DOI: 10.2106/JBJS.N.00654
• EISSN: 1535-1386
• ISSN: 0021-9355

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.