Green tea extract synergistically enhances the effectiveness of an antiresorptive drug on management of osteoporosis induced by ovariectomy in a rat model


Abstract

Antiresorptive drugs are effective for reducing bone loss in postmenopausal women, but their long-term application may be associated with adverse effects. The present study aimed to investigate the potential in vivo synergistic effects of green tea extract (GTE) and alendronate or raloxifene on the management of osteoporosis. Ovariectomized rats were fed orally with GTE, alendronate and raloxifene at different concentrations and various combinations for 4 weeks. Bone mineral density (BMD) at the lumbar spine, femur and tibia was monitored weekly using peripheral quantitative computed tomography. Bone microarchitecture in the left distal femur was analyzed using micro-CT, while serum biochemical levels were measured using ELISA kits at the end of the study. GTE alone effectively mitigated BMD loss and improved bone microarchitecture in rats. The co-administration of GTE and alendronate increased total BMD in the lumbar spine, femur and tibia. Particularly, GTE synergistically enhanced the effect of alendronate at a low dose on bone microarchitecture and decreased serum tartrate-resistant acid phosphatase. These findings imply that the dosage of certain antiresorptive agents could be reduced when they are administrated simultaneously with GTE, so that their adverse effects are minimized. The findings may be used to support the development of a new synergistic intervention between food therapy and pharmacotherapy on the management of osteoporosis in a long-term basis.

Keywords: alendronate; antiresorptive; green tea; osteoporosis; raloxifene.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Effect of GTE at different concentrations on the bone of osteoporotic rat after 4 weeks of treatment. (A) Mean of the ratio from baseline (Day 0) of total and Trab BMD in lumbar spine, distal femur and proximal tibia measured by pQCT; (B) Differences in BV/TV, Tb.N, Tb.Th and Tb.Sp at the metaphysis of the distal femur measured by micro-CT. The error bar represents the + SD. *P<0.05; **P<0.01; ***P<0.001 vs. OVX without treatment. GTE, green tea extract; OVX, ovariectomized; BV/TV, trabecular bone volume; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; Trab, trabecular; BMD, bone mineral density.
Figure 2
Figure 2
Changes of total BMD at different regions of rats co-treated with GTE and antiresorptive drugs. Mean of percentage changes from baseline (Week 0) of the total BMD at lumbar spine, proximal tibia and distal femur co-treated with (A) A and (B) R. The error bar represents the ±SD. Two-way ANOVA followed by Bonferroni''s correction. *P<0.05; **P<0.01; ***P<0.001. BMD, bone mineral density; GTE, green tea extract; OVC, ovariectomized; ns, not significant; L, low dose; H, high dose; A, alendronate; R, raloxifene.
Figure 3
Figure 3
Difference in microarchitectural properties at the distal femur of rats co-treated with GTE and antiresorptive drugs. Mean of trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) after 4 weeks of co-treatment with (A) A and (B) R. The error bar represents the + SD. *P<0.05; **P<0.01; ***P<0.001 vs. OVX without treatment. GTE, green tea extract; OVX, ovariectomized; BV/TV, trabecular bone volume; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; L, low dose; H, high dose; A, alendronate; R, raloxifene.
Figure 4
Figure 4
Difference in the concentration of bone turnover markers in the serum of rats treated with GTE and/or combinations of A. Mean of CTX, OC and TRAcP 5b concentration after 4 weeks of treatment with GTE and/or A. Error bar represents the + SD. *P<0.05; **P<0.01; ***P<0.001 vs. OVX without treatment. GTE, green tea extract; OVX, ovariectomized; L, low dose; H, high dose; A, alendronate; OC, osteocalcin CTX, C-terminal telopeptide; TRAcP 5b, tartrate-resistant acid phosphatase 5b.
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