Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model
, I. Kramer 2, F. Schlottig 3, N. Tödtmann 4, U. Eckelt 10, A. Bürki 5, S.J. Ferguson 6, A. Kautz 7, M. Schnabelrauch 7, U. Range 8, M. Kneissel 2, B. Stadlinger 91 Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Department of Oral and Maxillofacial Surgery, Berlin, Germany
2 Musculoskeletal Disease Area, Novartis Institute for Biomedical Research, Basel, Switzerland
3 School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland
4 Department of Oral and Maxillofacial Surgery, Ruhr Universität Bochum, Germany
5 Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland
6 Institute for Biomechanics, ETH Zurich, Switzerland
7 Innovent e.V. Biomaterials Department, Jena, Germany
8 Institute for Medical Informatics and Biometry, Technische Universität Dresden, Medical Faculty Carl Gustav Carus,Dresden, Germany
9 Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, University Hospital Zurich, Switzerland
10 Department of Oral and Maxillofacial Surgery, Medical Faculty “Carl Gustav Carus”, Technische Universität Dresden, Germany
Abstract
Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle,versussole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model.Uncoated reference surface implants or ZOL-coated implants (n =64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation byex vivoµCT, histology and biomechanical testing.Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants.In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.
Graphical Abstract
Keywords
- Dental implant
- osseointegration
- osteoporosis animal model
- sclerostin antibody
- zoledronic acid
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