Abstract
Aseptic loosening following periprosthetic osteolysis is the primary complication that limits the lifetime of total joint arthroplasty (TJA). The wear particles trigger a chronic inflammation response in the periprosthetic tissue and turn over the bone balance to bone resorption. The present study aimed to investigate the possible effect and mechanism of strontium ranelate (SR), a clinically safe drug for osteoporosis, on particle-induced periprosthetic osteolysis. Thirty-six female C57BL/6j mice underwent tibial Ti-nail implantation to establish an animal model of aseptic loosening. After 12 weeks, micro-CT results showed that strontium ranelate could inhibit periprosthetic bone resorption. In vitro, Ti particles were used to stimulate RAW264.7 cell line to collect conditioned medium, and co-culture MC3T3-E1 cell line with conditioned medium to establish a cell model of aseptic loosening. The results of alkaline phosphatase (ALP) detection, immunofluorescence, and flow cytometry demonstrated that strontium ranelate could regulate the expression of OPG/RANKL, promote differentiation and mineralization, and inhibit apoptosis in osteoblasts. Moreover, we revealed that SR’s exerted its therapeutic effect by down-regulating sclerostin, thereby activating the Wnt/β-catenin signal pathway. Therefore, this research suggests that strontium ranelate could be a potential drug for the prevention and treatment of particle-induced aseptic loosening post-TJA.
Highlights
Total joint arthroplasty (TJA) can effectively alleviate the pain caused by various joint diseases, and reconstruct the damaged joint function especially for the end-stage arthropathy
As a listed medication that was applied years ago in the treatment of osteoporosis, Strontium ranelate (SR) can effectively lower the risk of bone fracture in postmenopausal female patients [15,33]
We discovered that SR might inhibit in vivo and in vitro periprosthetic osteolysis induced by wear particles
Summary
Total joint arthroplasty (TJA) can effectively alleviate the pain caused by various joint diseases, and reconstruct the damaged joint function especially for the end-stage arthropathy. The long-term postoperative follow-up visits revealed a 20-year survival rate higher than 80% [1,2]. Aseptic loosening induced by wear particles has been identified as the primary cause for postoperative failure, accounting for approximately 75% of revision cases [3]. The number of patients with postoperative aseptic loosening has increased [4]. There is no effective treatment method other than complicated revision surgery. The previous studies suggested that the biological reaction between periprosthetic tissues and wear particles induces chronic inflammation, which in turn brakes the bone metabolic balance and leads to periprosthetic osteolysis [5,6]
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