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

Abstract

Implant-generated particle wears are considered as the major cause for the induction of implant loosening, which is more susceptible to patients with osteoporosis. Monotherapy with parathyroid hormone (PTH) or zoledronate acid (ZOL) has been proven efficient for preventing early-stage periprosthetic osteolysis, while the combination therapy with PTH and ZOL has exerted beneficial effects on the treatment of posterior lumbar vertebral fusion and disuse osteopenia. However, PTH and ZOL still have not been licensed for the treatment of implant loosening to date clinically. In this study, we have explored the effect of single or combined administration with PTH and ZOL on implant loosening in a rat model of osteoporosis. After 12 weeks of ovariectomized surgery, a femoral particle-induced periprosthetic osteolysis model was established. Vehicle, PTH (5 days per week), ZOL (100 mg/kg per week), or combination therapy was utilized for another 6 weeks before sacrifice, followed by micro-CT, histology, mechanical testing, and bone turnover examination. PTH monotherapy or combined PTH with ZOL exerted a protective effect on maintaining implant stability by elevating periprosthetic bone mass and inhibiting pseudomembrane formation. Moreover, an additive effect was observed when combining PTH with ZOL, resulting in better fixation strength, higher periprosthetic bone mass, and less pseudomembrane than PTH monotherapy. Taken together, our results suggested that a combination therapy of PTH and ZOL might be a promising approach for the intervention of early-stage implant loosening in patients with osteoporosis.

Regulation of bone homeostasis: signaling pathways and therapeutic targets

“… 338 Moreover, Ti particles inhibit the osteogenic differentiation of osteoblasts via the BMP/SMAD signaling pathway. 339 Furthermore, we found that titanium particles lead to an aberrant increase in GSK‐3β activity, which inhibits the Hh/Gli1 signaling pathway, ultimately leading to an inhibition of the osteogenic process. 7 Furthermore, we demonstrated that up‐regulation of SIRT3 expression enhanced the osteogenic differentiation of PPO289 by decreasing NLRP3 inflammasome expression via the GSK‐3β/β‐catenin signaling pathway.…”

A personalized biomimetic dual-drug delivery system via controlled release of PTH1-34 and simvastatin for in situ osteoporotic bone regeneration

“…PTH 1-34 interacts with PTH1R on the surface of osteoblasts and osteocytes and contributes to expanding the number of osteoblasts by reducing apoptosis and exerting an anabolic effect on bone ( Silva and Bilezikian, 2015 ; Chen et al, 2021 ). Previous studies have used PTH in combination with bisphosphonates to achieve better osteogenesis and reduce the amount of PTH in the treatment of osteoporosis ( Zhang and Song, 2020 ; Zhou et al, 2022 ). However, one risk of bisphosphonates is medication-related osteonecrosis of the jaw ( Pires et al, 2005 ).…”

Pre-implantation teriparatide administration improves initial implant stability and accelerates the osseointegration process in osteoporotic rats

“…After administered teriparatide for 12 weeks, new bone formation was found around external and internal surfaces of titanium implants in osteoporotic rabbits [ 6 ]. And following teriparatide treatment, osteoporotic SD rats also showed an increased value of maximal pull-out force as a sign of increased implant fixation [ 7 ]. Similarly, Li et al‘s investigation further showed how teriparatide treatment altered the peri-implant bone mass and density associated to an increase in implant fixation in osteoporotic rats by micro-CT and histological results [ 8 ].…”