Efficacy of a sclerostin antibody compared to a low dose of PTH on metaphyseal bone healing

• Published in: Journal of orthopaedic research Vol. 32; no. 3; pp. 471 - 476
• Main Authors: Agholme, Fredrik, Macias, Brandon, Hamang, Matt, Lucchesi, Jonathan, Adrian, Mary D., Kuhstoss, Stuart, Harvey, Anita, Sato, Masahiko, Aspenberg, Per
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2014
• Subjects: Animals; Antibodies - therapeutic use; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; bone formation; bone healing; Bone Morphogenetic Proteins - antagonists & inhibitors; Bone Morphogenetic Proteins - immunology; Bone Screws; Drug Evaluation, Preclinical; Fracture Healing - drug effects; Fractures, Bone - drug therapy; Genetic Markers - immunology; implant fixation; Male; mechanical testing; MEDICIN; MEDICINE; Random Allocation; Rats; Rats, Sprague-Dawley; Teriparatide - pharmacology; Teriparatide - therapeutic use; Wnt-signaling; implant fixation; bone formation; Wnt-signaling; mechanical testing; bone healing
• ISSN: 0736-0266; 1554-527X; 1554-527X
• DOI: 10.1002/jor.22525

ABSTRACT We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25 mg/kg, twice weekly) or PTH (5 µg/kg, daily). The healing response around the screws was then assessed by mechanical testing and X‐ray microtomography (µCT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull‐out force compared to control (p = 0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. µCT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide‐spread effects, mainly on cortical bone, with less influence on metaphyseal healing. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:471–476, 2014.