Anti-RANKL treatment improves screw fixation in cancellous bone in rats.
Bisphosphonates improve implant fixation in randomised clinical trials of knee prostheses, hip prostheses and dental implants. However, a limited amount of bone resorption is required for bisphosphonates to exert an effect. Anti-RANKL treatment does not have this limitation, and we therefore tested whether if they might be more effective for improvement of implant fixation. This is of interest, as anti-RANKL treatment with denosumab is now in common clinical use. Male SD rats received a stain-less steel screw in the right proximal tibia and a drill hole in the left (n = 42). They were randomised to subcutaneous injections of either alendronate (20 μg/kg/day), alendronate (200 μg/kg/day), osteoprotegerin with an Fc tag (OPG-Fc; 8 mg/kg, twice weekly), or saline control. After 4 weeks, the fixation of the steel screw was measured by pull-out test. The tibia with the drill hole was evaluated with μCT. OPG-Fc increased the pull-out force compared to saline controls by 153% (p < 0.001). There was no significant difference between OPG-Fc and the alendronate groups. OPG-Fc increased the bone density (BV/TV) in the previous drill hole compared to controls 7-fold (p < 0.001). This increase was higher than with any alendronate dose (p < 0.001). OPG-Fc increased the bone density of the L5 vertebral body, but there was no significant difference between OPG-Fc and alendronate. Our results suggest that screw fixation in cancellous bone can be dramatically improved by an anti-RANKL agent. The effect was comparable to very high bisphosphonate doses. Screw insertion in cancellous bone elicits a metaphyseal fracture healing response, and our findings might be relevant not only for implant fixation, but also for fracture healing in cancellous bone.
Orthopedics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences at Linköping University, SE-581 85 Linköping, Sweden.
Magnus
M
Bernhardsson
Orthopedics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences at Linköping University, SE-581 85 Linköping, Sweden.
Olof
O
Sandberg
Orthopedics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences at Linköping University, SE-581 85 Linköping, Sweden. Electronic address: per.aspenberg@liu.se.
Per
P
Aspenberg
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption; D004164:Diphosphonates / Q000494:pharmacology*; D017102:Fracture Healing / Q000187:drug effects; D008297:Male; D053244:Osteoprotegerin / Q000494:pharmacology*; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000473:pathology* / Q000601:surgery; D013978:Tibial Fractures / Q000473:pathology*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053244:Osteoprotegerin; D053245:RANK Ligand; D019386:Alendronate
Antiresorptives; Bisphosphonates; Denosumab; Fracture healing; Implant fixation; Rat model