Strontium-Doped Mesoporous Bioactive Glass-Loading Bisphosphonates Inhibit Osteoclast Differentiation and Prevent Osteoporosis in Ovariectomized Mice

Abstract

Postmenopausal osteoporosis, a metabolic bone disease associated with aging that affects bones throughout the body, is emerging as an urgent public health concern and imposes a substantial healthcare burden on society. The clinical application of bisphosphonate, the primary treatment for osteoporosis, is limited owing to the drug’s severe complications. Herein, we investigate the synthesis and utilization of strontium-doped mesoporous bioactive glass loaded with alendronate (ALN@Sr-MBG) as a novel therapeutic agent for osteoporosis, to explore its potential as an alternative to alendronate (ALN). Strontium-doped mesoporous bioactive glass (Sr-MBG) was synthesized using the sol–gel method, while ALN@Sr-MBG was obtained via incorporating Sr-MBG into an alendronate saturated solution. The bioactivities of ALN@Sr-MBG, including biotoxicity, inflammation inhibition, and anti-osteoclast differentiation, were investigated in vitro using CCK-8, flow cytometry, tartrate-resistant acid phosphatase (TRAP) staining, and RT-PCR assays. Animal models were established by surgically removing the ovaries from non-pregnant female C57/BL mice, followed by weekly intraperitoneal injections of ALN@Sr-MBG, ALN, or excipients. After 8 weeks, the mice femurs were extracted and analyzed through micro-CT scanning and hematoxylin-eosi, osteoblastic, and osteogenic staining. These in vitro findings demonstrate that ALN@Sr-MBG displays enhanced biological efficacy compared to ALN in terms of inflammation inhibition, osteogenesis promotion, and osteoclastogenesis inhibition. Furthermore, micro-CT analysis revealed that ALN@Sr-MBG significantly augments bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), while reducing trabecular separation (Tb.Sp) and the structural model index (SMI) in mice with ovariectomy-induced osteoporosis. The osteoblast and osteogenic staining results indicate the enhanced bioactivities of ALN@Sr-MBG in promoting bone formation and inhibiting bone resorption compared to ALN. In vitro and in vivo assessments further confirmed that ALN@Sr-MBG exhibits superior anti-osteoporotic bioactivity compared to ALN. This study’s findings confirm the potential of ALN@Sr-MBG as a novel alternative therapy to ALN and a drug candidate for the treatment of osteoporosis.