title: Microstimulation at the bone-implant interface upregulates osteoclast activation pathways.
abstract: Peri-implant bone resorption after total joint arthroplasty is a key parameter in aseptic loosening. Implant wear debris and biomechanical aspects have both been demonstrated to be part of the bone resorption process. However, neither of these two parameters has been clearly identified as the primary initiator of peri-implant bone resorption. For the biomechanical parameters, micromotions were measured at the bone-implant interface during normal gait cycles. The amplitude of the micromotions was shown to trigger differentiation of bone tissues. So far no data exists directly quantifying the effect of micromotion and compression on human bone. We hypothesize that micromotion and compression at the bone-implant interface may induce direct activation of bone resorption around the implant through osteoblasts-osteoclasts cell signaling in human bone. This hypothesis was tested with an ex vivo loading system developed to stimulate trabecular bone cores and mimic the micromotions arising at the bone-implant interface. Gene expression of RANKL, OPG, TGFB2, IFNG and CSF-1 was analyzed after no mechanical stimulation (control), exposure to compression or exposure to micromotions. We observed an 8-fold upregulation of RANKL after exposure to micromotions, and downregulation of OPG, IFNG and TGFB2. The RANKL:OPG ratio was upregulated 24-fold after micromotions. This suggests that the micromotions arising at the bone-implant interface during normal gait cycles induce a bone resorption response after only 1 h, which occurs before any wear debris particles enter the system.
authors.affiliation: Laboratory of Biomechanical Orthopedics EPFL-HOSR, Institute of Translational Biomechanics, Station 15, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Stadelmann
authors.forename: Alexandre
authors.initials: A
authors.lastname: Terrier
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Pioletti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016025:Bone Transplantation; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation