Effects of Preventive Long-Term Treatment with Strontium Ranelate and Zoledronic Acid on Bone Quality in Ovariectomized Rats

Abstract

The aim of this work was to study the effects on bone quality produced by long-range treatment with zoledronic acid (ZA) or strontium ranelate (SrR) in ovariectomized rats. Sixty 6-month-old female Wistar rats were divided: SHAM (n=15), simulated intervention; OVX (n=15), ovariectomized; OVX+ZA (n=15), ovariectomized treated with ZA (0.083 mg/kg i. v. at the beginning of the study); and OVX+SrR (n=15), ovariectomized treated with SrR (0.033 g/kg/day by oral gavage). Rats were sacrificed 8 months later. Femoral (F) and lumbar (L) bone mineral density (BMD), trabecular and cortical microstructure, biomechanical testing and Raman spectrometry were performed. FBMD and LBMD decreased in OVX rats with no changes with SrR. ZA treatment prevented changes to BMD. Ovariectomy produced a reduction in micro-CT parameters, while SrR treatment did not avoid these changes. ZA treatment increased micro-CT parameters with respect to the SHAM group. The microstructural parameters of the cortical region were not modified in any of the groups. Ovariectomy produced a decrease in biomechanical parameters that was maintained with SrR. ZA treatment produced an increase in these parameters being higher than those of the SHAM group. Ovariectomy and treatments did not produce differences in crystallinity or substitution index. Mineralization index (MI) decreased in the OVX group. SrR did not revert this effect though ZA avoided it. According to our results preventive treatment with SrR did not revert the alterations in bone quality due to ovariectomy in rats. Treatment with ZA not only reverted the effects of ovariectomy, but also improved bone quality with respect to control rats.

Efectos del tratamiento con bazedoxifeno sobre la calidad ósea en ratas ovariectomizadas

“…In a study carried out by our group 33 , we administered zoledronic acid to ovariectomized rats and we obtained much greater effects on increasing lumbar and femoral BMD on untreated rats than in the case of baze-doxifene. The rats' age conditions and ovariectomy time were totally similar to those in this study, so the results can be compared.…”