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抗骨质疏松药物对去负荷骨骨丢失的预防作用。

Effect of anti-osteoporotic agents on the prevention of bone loss in unloaded bone.

机构信息

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, P.R. China.

出版信息

Mol Med Rep. 2013 Oct;8(4):1188-94. doi: 10.3892/mmr.2013.1647. Epub 2013 Aug 20.

DOI:10.3892/mmr.2013.1647
PMID:23970373
Abstract

Pharmaceutical countermeasures to treat disuse osteoporosis are rarely studied. Pharmaceutical studies for the treatment and prevention of osteoporosis depend on the ovariectomized rat model, which is a suitable model for the disease in women. Disuse osteoporosis affects men and women, but there is lack of awareness and relevant pharmaceutical studies for this condition. The objectives of this study were to verify the validity of an unusual tail-suspension rat model in the induction of disuse osteoporosis and subsequent pharmaceutical treatments. This model was created by unloading the hind limbs of the rats in order to create a state of weightlessness in their hindlimb bones. Validation of the model was performed with non-suspended rats. This study included five groups of suspended rats fed with different agents, such as distilled water (control), high-, medium- and low-dose raloxifene and a bisphosphonate (alendronate). The experiment lasted for 28 days. Comparisons were made between the suspended control and treatment groups. Ovariectomized and sham‑operated rats were also included as a reference for bone changes during osteoporosis. Changes in bone mineral density (BMD) at the distal femur and proximal tibia, microarchitecture at the distal femur and biomechanical strength at the diaphyseal femur were studied. Reduction of BMD and deterioration of trabeculae were similar between the suspended control and ovariectomized rats. Loss of BMD induced by tail suspension was reduced most effectively by medium-dose raloxifene. Deterioration of trabecular microarchitecture was also prevented by raloxifene. The tail-suspension rat model is suitable for the study of disuse osteoporosis under the effects of various therapeutic agents. The preventive effects of raloxifene against bone loss under disuse conditions have been demonstrated using this model.

摘要

用于治疗废用性骨质疏松症的药物对策很少被研究。治疗和预防骨质疏松症的药物研究依赖于去卵巢大鼠模型,该模型是女性疾病的合适模型。废用性骨质疏松症影响男女,但对此病症缺乏认识和相关药物研究。本研究的目的是验证一种不寻常的尾部悬吊大鼠模型在诱导废用性骨质疏松症及随后的药物治疗中的有效性。该模型通过使大鼠的后肢卸载来创建其后肢骨骼失重的状态。通过未悬吊的大鼠来验证模型的有效性。本研究包括五个悬吊大鼠组,分别给予不同的药物处理,如蒸馏水(对照)、高、中、低剂量雷洛昔芬和一种双膦酸盐(阿伦膦酸钠)。实验持续 28 天。比较悬吊对照组和治疗组。还包括去卵巢和假手术大鼠作为骨质疏松症期间骨变化的参考。比较了远端股骨和近端胫骨的骨矿物质密度(BMD)、远端股骨的微结构和骨干的生物力学强度的变化。悬吊对照组和去卵巢大鼠的 BMD 减少和小梁恶化相似。中等剂量雷洛昔芬最有效地减少了由尾部悬吊引起的 BMD 损失。雷洛昔芬还可防止小梁微结构恶化。尾部悬吊大鼠模型适合于研究各种治疗药物对废用性骨质疏松症的影响。该模型证明了雷洛昔芬对废用条件下骨丢失的预防作用。

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