Zoledronic acid and teriparatide have a complementary therapeutic effect on aseptic loosening in a rabbit model

Abstract

Abstract Background Revisions are mainly caused by wear debris-induced aseptic loosening. How to effectively suppress debris-induced periprosthetic osteolysis has become an urgent problem. Both zoledronic acid and teriparatide can increase the bone mass around prostheses and increase the stability of prostheses. A hypothesis was proposed: the combination of the two drugs may have a better treatment effect than the use of either drug alone. Methods We created a rabbit model to study the effect and mechanism of the combination of zoledronic acid and teriparatide in the treatment of aseptic loosening. Thirty-two adult male New Zealand white rabbits were selected and treated with TKA surgery, and a titanium rod prosthesis coated evenly with micrometre-sized titanium debris was implanted into the right femoral medullary cavity. All rabbits were randomized into four groups (control group = 8, zoledronic acid group = 8, teriparatide group = 8, and zoledronic acid + teriparatide group = 8). All the animals were sacrificed in the 12th week, and X-ray analyses, H&E staining, Goldner-Masson trichrome staining, von Kossa staining, and RT-PCR and Western blotting of the mRNA and protein of OCN, OPG, RANKL and TRAP5b in the interface membrane tissues around the prostheses were immediately carried out. Results The results shown that both zoledronic acid and teriparatide could inhibit debris-induced peri-prosthetic osteolysis and promote new bone formation. Zoledronic acid was more capable of inhibiting osteoclast activation and peri-prosthetic osteolysis, while teriparatide was more capable of promoting osteoblast function and peri-prosthetic bone integration. Conclusion This research confirmed that the combination of zoledronic acid and teriparatide could prevent and treat aseptic loosening of the prosthesis more effectively. However, the safety of this combination and the feasibility of long-term application have not been ensured, and the clinical application requires further experiments and clinical research support.