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

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.

Additive Effect of Parathyroid Hormone and Zoledronate Acid on Prevention Particle Wears-Induced Implant Loosening by Promoting Periprosthetic Bone Architecture and Strength in an Ovariectomized Rat Model

“…Several nationwide clinical studies clarified that bisphosphonate in patients with THA exhibited a lower risk for revision surgery, indicating that bisphosphonate use is encouraged in patients suffering from osteoporosis and candidates for THA ( 25 , 36 ). Animal studies also proved that both local and system administrations of bisphosphonate displayed a capacity to prevent particle-induced osteolysis by diminishing bone loss and fiber formation ( 18 , 19 , 32 ). In this study, the systemic administration of ZOL has not improved implant anchorage compared with the O+T group.…”

“…Additionally, intermittent parathyroid hormone (PTH) 1-34 is another classical mediation for the treatment of osteoporosis, with the capacity of anabolic effects. Our and other research groups have revealed that intermittent PTH treatment could prevent particle-induced osteolysis in vivo ( 17 – 19 ). Recently, several cases reported that PTH has a protective effect on prosthetic loosening clinically ( 20 – 22 ).…”

“…Particularly, agents targeting at regulating bone metabolism have been found effective on implant loosening prevention in animal models, such as sclerostin antibody, alendronate ( 14 , 29 ). Our group has previously proved the protective effect of intermittent PTH administration or weekly ZOL injection on periprosthetic osteolysis, indicating that these were potential ways to prevent implant loosening ( 17 , 19 , 32 ). Additionally, clinical case reports and trials also provided evidence that agents (such as denosumab and PTH) inhibited periprosthetic bone loss and improved early-stage implant loosening after arthroplasty ( 20 , 21 , 33 ).…”

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

“…Particulate wear debris from implants can spread in the joint cavity and surface, and induce intricate biological responses including PPO and aseptic loosening [ 27 ]. As we know, wear particle can stimulate macrophages, T lymphocytes, fibroblasts, and foreign body giant cells to secrete TNFα, IL-1β, IL-6, prostaglandin E2, and other proinflammatory cytokines.…”

Nano Sized Gallium Oxide Surface Features for Enhanced Antimicrobial and Osteo-Integrative Responses

“…Surface engineering of the implant is a key strategy in overcoming aseptic loosening and research is being directed towards novel materials or enhancement of existing materials by doping with active materials that control osteoclasts and enhance osteoblast formation. [11][12][13] Current non-cemented knee or hip implants are generally cobalt-chromium or titanium alloys, often with a pre-deposited hydroxyapatite (HA) coating for improved osteointegration. [14,15] Inorganic doping of HA with elements such as strontium, silver, europium and zinc can induce a preferential biological response.…”