Sclerostin Antibody Treatment Improves Implant Fixation in a Model of Severe Osteoporosis. (21st January 2015)

• Record Type: Journal Article
• Authors: Virdi, Amarjit S.; Irish, John; Sena, Kotaro; Liu, Min; Ke, Hua Zhu; McNulty, Margaret A.; Sumner, Dale R.
• Is Part Of: Journal of bone and joint surgery. Volume 97:Number 2(2015)
• Publication Date: 2015-01-21
• Subjects: Bones -- Surgery -- Periodicals; Joints -- Surgery -- Periodicals; Orthopedics -- Periodicals; Orthopedics; General Surgery; Bone Diseases; Joint Diseases; Bones -- Surgery; Joints -- Surgery; Orthopedics; Bot (anatomie); Gewrichten; Chirurgie (geneeskunde); Periodicals; Electronic journals; Periodicals; 617.47005
• DOI: 10.2106/JBJS.N.00654
• Languages: English
• ISSNs: 0021-9355

Abstract

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.