Antiresorptive Agents are More Effective in Preventing Titanium Particle‐Induced Calvarial Osteolysis in Ovariectomized Mice Than Anabolic Agents in Short‐Term Administration

Abstract

Aseptic loosening due to wear particle‐induced osteolysis is the main cause of arthroplasty failure and the influence of postmenopausal osteoporosis and anti‐osteoporosis treatment on Titanium (Ti) particle‐induced osteolysis remains unclear. 66 C57BL/6J female mice were used in this study. Ovariectomy (OVX) was performed to induce osteopenia mice and confirmed by micro‐CT. The Ti particle‐induced mouse calvaria osteolysis model was established subsequently and both OVX and Sham‐OVX mice were divided into four groups, respectively: Ti (‐) group, Ti group, Ti + zoledronic acid (ZOL) group (50ug/kg, local administration, single dose) and Ti + teriparatide (TPTD) group (40ug/kg/d, subcutaneous injection*14d). Mice calvarias were collected for micro‐CT and histomorphometric analysis 2 weeks after particle induction. 8 weeks after bilateral OVX, significantly reduced BMD and microstructure parameters in both proximal tibia and calvaria were observed in OVX mice when comparing with Sham‐OVX mice. OVX mice in Ti group had not only markly decreased BMD and BV/TV, but also significantly increased total porosity, eroded surface area and osteoclast numbers when comparing with Sham‐OVX mice. Shown by Two‐way ANOVA analysis, the interaction terms between OVX and Ti implantation on micro‐CT and histomorphometry parameters didn’t reach significant difference. As illustrated by micro‐CT and histological analysis, ZOL treatment markedly inhibited Ti particle‐induced osteolysis in OVX mice and Sham‐OVX mice, and there were significant differences when comparing to both Ti and Ti+TPTD group. The combination of osteoporosis and Ti particle implantation result in aggravated bone resorption, accompanied with increased osteoclasts and excessive inflammation response. ZOL was more effective in preventing Ti particle‐induced osteolysis in both OVX mice and Sham‐OVX mice than TPTD in short‐term administration. ZOL exert the protective effects on Ti particle‐induced bone loss via the suppression of osteoclasts.

Titanium Wear Particles Exacerbate S. epidermidis-Induced Implant-Related Osteolysis and Decrease Efficacy of Antibiotic Therapy

“…Indeed, sterile implanted screws in the presence of WPs displayed minimal changes to bone parameters as assessed by longitudinal microCT scanning. This is in contrast with numerous in vivo studies demonstrating osteolytic responses to WPs in the absence of bacterial infection [35][36][37], although this likely reflects the prevalence and specific experimental context of the murine calvarial osteolytic model that is widely used for assessing WP-induced osteolysis. The contribution of bacterial-derived endotoxins for driving osteolytic responses, either due to the use of contaminated WPs, or via binding from systemic sources following WP implantation [38], appears to be a major stimulus for WP-induced osteolysis [39][40][41].…”

Importance of Routine Bone Mineral Density Screening Prior to Elective Total Joint Replacement

“…16 Further, several studies suggest that treatment of osteoporosis with bisphosphonates for patients with osteoarthritis may reduce the need for TJR, potentially through n guest editorial antiresorptive effects that minimize periprosthetic bone loss and osteolysis. 17,18 Despite the potential benefits of knowing patients' BMD status prior to and following TJR, there is a significant gap between national screening guidelines for BMD and clinical practice, with significant underutilization of dual-energy x-ray absorptiometry screening in primary care settings. 19,20 The US Preventive Services Task Force recommends screening for osteoporosis with BMD testing to prevent osteoporotic fractures in women 65 years and older and in postmenopausal women younger than 65 years who are at increased risk of osteoporosis.…”

Hepcidin-induced reduction in iron content and PGC-1β expression negatively regulates osteoclast differentiation to play a protective role in postmenopausal osteoporosis

“…Although some studies suggested that dose control did not increase the incidence of breast and cervical cancer, osteoporosis patients with breast cancer have been prohibited from using hormone replacement therapy [ 32 ]. Other studies have found that the cause of postmenopausal osteoporosis was the abnormal activation of osteoclasts, and as the osteogenic drug PTH cannot alleviate osteolysis, it was not suitable for the treatment of postmenopausal osteoporosis [ 33 ]. Therefore, it could be of great clinical significance to find a supplementary treatment method for postmenopausal osteoporosis.…”