Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy.
Phytomedicine. 2011 Jul 15;18(10):879-86. doi: 10.1016/j.phymed.2011.02.003. Epub 2011 Mar 11.
Genistein aglycone (GEN) has a favorable effect on bone loss. We investigated the effects of GEN alone or in combination with supplemental calcium and vitamin D(3) in an animal model of bone loss to evaluate if there was additional benefit. Ovariectomized (OVX) and SHAM-OVX rats were used. OVX were divided into 12 groups and randomized to receive: GEN at 27, 54, 200, 500 or 1000 mg (human equivalent dose (HED)/day/ip injection alone or with calcium carbonate (Ca) (360 mg/kg/day/gavages) and vitamin D(3) (D(3)) (50 IU/kg/day/gavages) or Ca/D(3) without GEN or untreated for 6 weeks. SHAM-OVX were randomized into 7 groups and treated with: Ca and D(3) alone or in combination with GEN (same doses as OVX), or left untreated. Bone mineral density (BMD), bone-alkaline phosphatase (b-ALP), collagen C-telopeptides (CTX), osteoprotegerin (OPG) and soluble receptor activator of NFκB ligand (sRANKL) were assessed. Femurs were excised and tested for breaking strength and histology. Uterine weight was analyzed to assess GEN's estrogenic effects on the SHAM-OVX. The most effective dose of GEN, independent of Ca/D(3) supplementation, was 54 mg/day. Higher doses yielded no further improvement in bone biomarkers, histology or strength. Only 1000 mg/day HED of genistein produced statistically significant changes in uterine weight of the SHAM-OVX. This study suggests that 54 mg/day of GEN is the threshold dose for efficacy. In addition, supplemental calcium and vitamin D(3), beyond normal dietary intake do not enhance the effects of genistein on improving measures of bone loss. This observation has implications regarding the use of calcium and vitamin D(3) supplementation.
染料木黄酮苷元（GEN）对骨质流失有有益作用。我们在骨质流失动物模型中研究了 GEN 单独或与补充钙和维生素 D(3)联合应用的效果，以评估是否有额外的益处。使用去卵巢（OVX）和假手术去卵巢（SHAM-OVX）大鼠。OVX 分为 12 组，随机接受：GEN 27、54、200、500 或 1000 mg（人等效剂量（HED）/天/ip 注射，单独或与碳酸钙（Ca）（360 mg/kg/天/灌胃）和维生素 D(3)（D(3)）（50 IU/kg/天/灌胃）或无 GEN 的 Ca/D(3)或未治疗 6 周。SHAM-OVX 随机分为 7 组，接受：Ca 和 D(3)单独或与 GEN（OVX 相同剂量）联合治疗，或未治疗。测定骨矿物质密度（BMD）、骨碱性磷酸酶（b-ALP）、胶原 C 端肽（CTX）、骨保护素（OPG）和可溶性核因子 κB 配体受体激活剂（sRANKL）。切除股骨并进行断裂强度和组织学测试。分析子宫重量以评估 GEN 对 SHAM-OVX 的雌激素作用。与 Ca/D(3)补充无关，GEN 的最有效剂量为 54mg/天。更高剂量不会进一步改善骨生物标志物、组织学或强度。只有 GEN 的 1000mg/天 HED 剂量会导致 SHAM-OVX 的子宫重量发生统计学上的显著变化。本研究表明，54mg/天的 GEN 是疗效的阈值剂量。此外，补充钙和维生素 D(3)，超过正常饮食摄入，不会增强 GEN 改善骨质流失措施的效果。这一观察结果对钙和维生素 D(3)补充的应用具有重要意义。
