Abstract
Purpose/ObjectivePrompted by preliminary findings, this study was conducted to investigate the impact of zoledronic acid on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.Methods and Materials96 8-week-old specific-pathogen-free C57BL/6 mice were randomly divided into 4 groups (24 per group): a sham group, an ovariectomized osteoporosis model group, an estradiol-treated group, and a zoledronic acid-treated group. Five months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional imagery of their cancellous bone microstructure. The impact of ovariectomy, the effect of estradiol, and the effect of zoledronic acid intervention on cancellous bone microstructure, as well as on the expression of β-catenin, were evaluated.ResultsThe estradiol-treated and the zoledronic acid-treated group exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickness, bone surface to bone volume ratio (BS/BV), and β-catenin expression, when compared with those of the control group (P <0.01). In contrast, the structure model index, trabecular separation, and BS/BV were significantly lower compared with those of the model group (P <0.01). No differences were observed in the above parameters between animals of the zoledronic acid-treated and the estradiol-treated group.ConclusionThese results suggest that increased β-catenin expression may be the mechanism underlying zoledronic acid-related improvement in the cancellous bone microstructure in ovariectomized mice. Our findings provide a scientific rationale for using zoledronic acid as a therapeutic intervention to prevent bone loss in post-menopausal women.
Highlights
Osteoporosis has often been evaluated by measuring the mass of mineral per unit volume of bone, or bone mineral density (BMD)
The estradiol-treated and the zoledronic acid-treated group exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickness, bone surface to bone volume ratio (BS/BV), and β-catenin expression, when compared with those of the control group (P
These results suggest that increased β-catenin expression may be the mechanism underlying zoledronic acid-related improvement in the cancellous bone microstructure in PLOS ONE | DOI:10.1371/journal.pone
Summary
Osteoporosis has often been evaluated by measuring the mass of mineral per unit volume of bone, or bone mineral density (BMD). Various methods for BMD measurement have been developed, including X-ray measurements, radiographic absorptiometry (RA), single-photon absorptiometry (SPA), dual-photon absorptiometry (DPA), single-energy X-ray absorptiometry (SEXA), and dual-energy X-ray absorptiometry (DEXA) [1]. The accuracy of these measurements has gradually improved. The pathological changes caused by osteoporosis occur mainly in cancellous bone, a structure of interconnected rods and plates that form a three-dimensional branching lattice [6]. The assessment of microstructural changes in cancellous bone is a key element in the study of osteoporotic fracture and the evaluation of antiosteoporotic agents [7]. Micro-CT allows 3-dimension (3-D) analysis of bone density and microstructure and allows us to assess the structure and functionality of the bone through assessment of the trabecular structure [9,10,11]
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