The effects of zoledronic acid treatment and endurance exercise on ovariectomy-induced osteopenia in Wistar rats

Background This study investigated the effects of endurance exercise training and zoledronic acid (Zol) treatment on ovariectomy-induced osteopenia. Methods Middle-aged female Wistar rats were subjected to sham and ovariectomy surgeries and assigned to seven different groups according to Zol treatment doses and treadmill endurance exercise (Ex) training; these were the Sham, Ovx, Ovx + LowZ, Ovx + HighZ, Ovx + Ex, Ovx + LowZ + Ex, Ovx + HighZ + Ex groups. The subcutaneous doses for the low- and high-Zol-treated ovariectomized rats were 20 and 100 mu g/kg, respectively. Total intervention period was 10 weeks. Results When comparing the Ovx groups to the Sham group, ovariectomy resulted in multiple compromises in bone histomorphometry, size-related measurements, and biomechanical properties. Two-way ANOVA was adopted to investigate the effects of Zol treatments and Ex on the six ovariectomized groups. In spongy bone histomorphometry, Zol treatment resulted in comprehensive preservation for all parameters, while exercise demonstrated benefits for osteoclastic number and mineralization activity. In serum marker assays, the Zol-treated rats had lower serum osteocalcin and IGF-1/IGFBP-3 molar ratio when compared to the non-treated rats. Exercise training significantly benefited metabolism through lower serum triglycerides, cholesterol, leptin, IGF-1 and IGF-1/IGFBP-3 molar ratio, along with increased IGFBP-3 and phosphorus (p < 0.05). In bone-size-related measurements and biomechanical property analyses, data were normalized to body weight. For whole bone strength, Zol treatments demonstrated higher bone fracture load (FL) and FL energy, while Ex showed benefits to yield load, FL, post-yield load energy, and stiffness. In tissue-level biomechanical properties, rats treated with the higher Zol dose were higher in yield stress and yield toughness. Exercise benefited most bone-size-related measurements, while the high Zol-treated rats showed smaller medullar area. Conclusion When combined with Zol treatments, exercise training did not demonstrate significant collaborative or modifying effects. Exercise and bisphosphonate tend to affect to bone through distinct pathways. A lower dose or different timing of Zol treatment or during a later phase of bisphosphonate treatment (drug holiday) might allow the occurrence of synergistic effects between Zol treatment and exercise.