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

Marta Martín-Fernández

doi:10.11648/j.ajcem.20160406.16

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.

Highlights

Due to the prevalence and severe consequences of postmenopausal osteoporosis, many pharmacological treatments have been developed to prevent or treat the disease
Postmenopausal osteoporosis is a chronic disease that exerts a significant burden on both individuals and the community
The present work shows that long-term (8 months) treatment with these 2 agents produce different effects on bone mineral density (BMD) in OVX rats

Summary

Introduction

Due to the prevalence and severe consequences of postmenopausal osteoporosis, many pharmacological treatments have been developed to prevent or treat the disease. The drugs developed for these purposes can be classified into 3 main groups: bone resorption inhibitors, formation stimulators, and those with dual effects, which. Within the group of agents that inhibit bone resorption, oral bisphosphonates have gained consideration over recent years as a first-line treatment option for osteoporosis, binding to bone and inhibiting osteoclast function. Poor adherence is a well-known problem with osteoporosis treatment [1]. For this reason, administration of bisphosphonates has been changed to weekly or monthly dosing, and ibandronate is available as an intravenous injection every 3 months. Zoledronic acid (ZA) is the only bisphosphonate that has been developed exclusively for intravenous use, featuring an attractive regimen of annual infusions for the treatment of osteoporosis, thereby ensuring therapeutic adherence [2]

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