Poly (methyl methacrylate) (PMMA) bone cement is widely used in percutaneous vertebroplasty to stabilize osteoporotic vertebral compression fractures. However, its clinical application is limited by its high compressive modulus, risk of thermal necrosis, and poor bone integration, unlike conventional PMMA formulations used in vertebrae or joint arthroplasty, which can reach polymerization temperatures exceeding 100 °C. Spine-specific PMMA is formulated to cure at a reduced polymerization temperature, thereby minimizing the rise in core temperature during the setting process. Consistent with our hypothesis, this moderate thermal output induces localized thermal injury that triggers osteogenic responses and extracellular matrix production, thereby enhancing osteoblast activity in the surrounding bone. This study aimed to evaluate bone remodeling following spine-specific PMMA injection in an osteoporotic Sprague-Dawley (SD) rat model. Twenty-four osteoporotic female SD rats were randomly assigned to three groups: Control (untreated), OVX + spine-specific PMMA (OVX + PMMA), and OVX (OVX + Defect). Bone regeneration was assessed using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (Micro-CT), quantitative PCR (qPCR), immunohistochemistry (IHC), and Western blotting. At 12 weeks post-injection, the OVX + PMMA group exhibited significantly greater bone regeneration than the OVX group. Micro-CT analysis demonstrated a marked increase in trabecular thickness in the PMMA-treated group. Notably, bone formation was more pronounced in regions surrounding the cement compared to adjacent untreated areas. This suggests that spine-specific PMMA promotes osteogenesis via localized thermal necrosis and subsequent osteoblast recruitment. These findings highlight the dual role of spine-specific PMMA in both structural stabilization and biologically driven bone regeneration. Further research is warranted to optimize its clinical applications while minimizing potential adverse effects.