Local strontium release from titanium implants and systemic sclerostin antibody synergistically improve biomechanical...

Osteoporosis compromises implant fixation by deteriorating peri-implant bone quality. This study investigated the combined effects of alkali heat-modified strontium-loaded titanium (Sr-Ti) implants and systemic sclerostin antibody (Scl-Ab; romosozumab) on osseointegration in an ovariectomized (OVX) rat model. Ti or Sr-Ti rod implants were inserted into the distal femur 12 weeks after OVX, followed by subcutaneous administration of Scl-Ab or vehicle for 4 or 8 weeks (Ti, Sr, Scl-Ti, and Scl-Sr groups; n = 5-6/group/time point). Outcomes included push-out biomechanical testing, micro-CT-based trabecular and cortical morphometry, histology for the bone-implant contact (BIC) ratio, and histomorphometry for the mineral apposition rate (MAR). At 4 weeks, the combined Scl-Sr group showed significantly higher push-out strength (128.8 ± 49.6 N) than the Ti (30.6 ± 7.4 N), Sr (63.2 ± 19.7 N), and Scl-Ti (61.6 ± 19.5 N) groups. At 8 weeks, Scl-Sr maintained the highest fixation strength (216.2 ± 38.7 N). Scl-Ab improved bone volume/tissue volume, trabecular number, cortical thickness, and the BIC ratio, indicating systemic effects, whereas Sr-Ti increased the BIC ratio, indicating primarily local effects. MAR was transiently elevated in Scl-Ab-treated groups at 4 weeks but normalized by 8 weeks. These findings demonstrate a synergistic interaction between local Sr ion delivery from implant surfaces and systemic Scl-Ab treatment on biomechanical fixation in osteoporotic bone. This dual-modality strategy, combining a bioactive Sr-Ti implant surface with systemic Scl-Ab, represents a promising approach for overcoming implant fixation challenges in osteoporosis.