Ethan M Lotz1, Christoph H Lohmann2, Barbara D Boyan1,3, Zvi Schwartz1,4. 1. Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA. 2. Department of Orthopaedics, Otto-von-Guericke-University, Magdeburg, Germany. 3. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA. 4. Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Abstract
Bisphosphonates (BPs) target osteoclasts, slowing bone resorption thus providing rationale to support osseointegration. However, BPs may negatively affect osteoblasts, impairing peri-implant bone formation. The goal of this study was to assess the effects BPs have on surface-mediated osteogenesis of osteoblasts. MG63 cells were cultured on 15-mm grade 2 titanium disks: smooth, hydrophobic-microrough, or hydrophilic-microrough (Institut Straumann AG, Basel, Switzerland). Tissue culture polystyrene (TCPS) was used as a control. At confluence, cells were treated with 0, 10-8 , 10-7 , and 10-6 M of alendronate, zoledronate, or ibandronate for 24 hr. Sprague Dawley rats were also treated with 1 μg/kg/day ibandronate or phosphate-buffered saline control for 5 weeks. Calvarial osteoblasts (rat osteoblasts [rOBs]) were isolated, characterized, and cultured on surfaces. Osteogenic markers in the media were quantified using ELISAs. BP treatment reduced osteocalcin, osteoprotegerin, osteopontin, bone morphogenetic protein-2, prostaglandin E2 , transforming growth factor β1, interleukin 10, and vascular endothelial growth factor in MG63 cells. The effect was more robust on rough surfaces, and higher concentrations of BPs stunted production to TCPS/PT levels. Ibandronate conditioned rOBs produced less osteogenic markers similar to direct BP treatment. These results suggest that BP exposure jeopardizes the pro-osteogenic response osteoblasts have to microstructured surfaces. Their effects persist in vivo and negatively condition osteoblast response in vitro. Clinically, BPs could compromise osseointegration.
Bisphosphonates (pan class="Chemical">BPs) target osteoclasts, slowing bone resorption thus providing rationale to support osseointegration. However, BPs may negatively affect osteoblasts, impairing peri-implant bone formation. The goal of this study was to assess the effects BPs have on surface-mediated osteogenesis of osteoblasts. MG63 cells were cultured on 15-mm grade 2 titanium disks: smooth, hydrophobic-microrough, or hydrophilic-microrough (Institut Straumann AG, Basel, Switzerland). Tissue culture polystyrene (TCPS) was used as a control. At confluence, cells were treated with 0, 10-8 , 10-7 , and 10-6 M of alendronate, zoledronate, or ibandronate for 24 hr. Sprague Dawley rats were also treated with 1 μg/kg/day ibandronate or phosphate-buffered saline control for 5 weeks. Calvarial osteoblasts (rat osteoblasts [rOBs]) were isolated, characterized, and cultured on surfaces. Osteogenic markers in the media were quantified using ELISAs. BP treatment reduced osteocalcin, osteoprotegerin, osteopontin, bone morphogenetic protein-2, prostaglandin E2 , transforming growth factor β1, interleukin 10, and vascular endothelial growth factor in MG63 cells. The effect was more robust on rough surfaces, and higher concentrations of BPs stunted production to TCPS/PT levels. Ibandronate conditioned rOBs produced less osteogenic markers similar to direct BP treatment. These results suggest that BP exposure jeopardizes the pro-osteogenic response osteoblasts have to microstructured surfaces. Their effects persist in vivo and negatively condition osteoblast response in vitro. Clinically, BPs could compromise osseointegration.
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