Osteoporotic vertebral compression fractures (OVCFs) are common complications of osteoporosis and contribute to significant morbidity in aging populations. Percutaneous vertebroplasty using polymethyl methacrylate (PMMA) bone cement provides stabilization, but conventional PMMA has limitations, including high stiffness, poor osteointegration, and excessive polymerization temperatures (>100 °C) that may cause thermal necrosis. To address these drawbacks, spine-specific PMMA was developed to polymerize at a reduced temperature (~47.5 °C), potentially minimizing tissue damage while harnessing localized mild heat to stimulate osteogenesis. This study evaluated whether spine-specific PMMA promotes bone regeneration in an ovariectomized (OVX) rat model.

Methods: Twenty-four female Sprague–Dawley rats (8 weeks old) were assigned to three groups: untreated control, OVX with defect, and OVX with PMMA injection. Eight weeks after bilateral ovariectomy, spine-specific PMMA was injected into caudal vertebrae (L3–L5). Animals were evaluated 12 weeks later. Bone regeneration was assessed using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (Micro-CT), quantitative PCR, Western blotting, and immunohistochemistry. Osteoblast and osteoclast activity were analyzed by protein markers and TRAP staining.

Results: DXA showed marked bone loss in OVX rats, whereas PMMA-treated animals demonstrated partial recovery of bone mineral density and content. Micro-CT revealed severe trabecular deterioration in OVX rats, while the PMMA group exhibited significantly higher bone volume fraction and trabecular thickness. Bone formation was most pronounced adjacent to cement deposits. Gene and protein analyses confirmed upregulation of osteogenic markers (ALP, RUNX2, OCN) in the PMMA group, exceeding control levels. Immunohistochemistry localized osteoblast activity to the cement–bone interface, and TRAP staining indicated reduced osteoclast activity compared with untreated OVX rats. Mechanistically, moderate localized thermal necrosis appeared to recruit osteoblasts via heat shock proteins (HSP70) and ERK/Wnt signaling pathways, supporting enhanced osteogenesis.

Conclusion: Spine-specific PMMA provides mechanical stabilization and simultaneously induces biologically favorable bone remodeling through controlled thermal effects. Unlike conventional PMMA, it promotes osteoblast activity and extracellular matrix production while limiting excessive necrosis. These findings suggest that low-temperature PMMA may represent a paradigm shift in managing OVCFs by combining structural stability with osteogenic stimulation. Further validation in large animal studies and clinical trials is warranted to optimize its safety, handling, and potential combination with osteoanabolic agents.