Biological Effect of Single or Combined Pharmacological Therapy Using Alendronate and Simvastatin on Implant Osseointegration: An In Vivo Study in Healthy and Osteoporotic Rat Models

Abstract

To evaluate peri-implant bone formation following single or combined systemic administration of alendronate and simvastatin in healthy and osteoporotic rats, eighty female Wistar rats were ovariectomized (n = 40) or sham-operated (n = 40). At six weeks, implants were placed in femoral condyles. Then, ovariectomized (OVX) and sham-operated (SHAM) animals received daily subcutaneous alendronate (50 µg/kg), simvastatin (5 mg/kg), or both, for three weeks. Control animals received subcutaneous saline. Thereafter, specimens were retrieved for biomechanical testing, histological evaluation, and bone area (BA%) and bone-to-implant contact (BIC%). In healthy and osteoporotic rats, similar (p > 0.05) push-out values were observed for all groups. For BA% analysis, control rats showed similar results for OVX (9.2% ± 2.4%) and SHAM (11.1% ± 3.5%) animals. In contrast, single or combined drug therapy significantly increased BA% compared to controls in both healthy and osteoporotic conditions (p < 0.05). In osteoporotic conditions, alendronate alone showed a superior effect on BA% compared to simvastatin alone, or their combination. Systemic alendronate, simvastatin, or both showed a similar BIC% compared to controls (p > 0.05). The present study demonstrates that single or combined systemic alendronate and simvastatin increases bone formation around implants (i.e., distance osteogenesis) in healthy and osteoporotic bone conditions. However, these drugs showed no beneficial effect on direct bone-to-implant contact or implant fixation.