Department of Biochemistry, Faculty of Pharmacy, Tanta University, Gharbia, 31527, Egypt.
Fundam Clin Pharmacol. 2013 Oct;27(5):526-34. doi: 10.1111/j.1472-8206.2012.01047.x. Epub 2012 Jul 4.
Osteoporosis is a reduction in bone mineral density (BMD). It develops less often in men than in women. This study aimed to evaluate the bone protective effects of raloxifene (RAL), risedronate (RIS), and their combination on osteoporotic male rats. Forty male Wister rats (12 weeks) were randomly divided into five groups: sham-operated group (n = 8), orchidectomized (ORX) group (n = 7), RAL group (n = 9), RIS group (n = 7) and RAL + RIS group (n = 7). RAL was orally administered at 3 mg/kg three times/week, and RIS was given subcutaneously at 5 μg/kg, twice weekly. After 6 weeks of treatment, serum cathepsin-K, alkaline (ALP) and acid phosphatase activities, serum osteocalcin, serum Ca²⁺, and Pi were determined. Urinary Ca²⁺ and deoxypyridinoline levels, BMD, and Ca²⁺ content of femur ash were estimated. Histochemical localization of ALP activity of tibia and histomorphometry was examined. As compared to sham, ORX rats showed a significant increase in bone turnover markers, and histochemical activity of ALP was increased markedly in proximal tibia of ORX rats, whereas BMD and Ca²⁺ content of femur ash were reduced after ORX. These changes were modulated after treatment with RAL and RIS or both to ORX rats; BMD of femur was improved by each treatment, and bone turnover markers were reduced as compared to ORX vehicle group. We concluded that orchidectomy induced osteoporosis and increased bone turnover in male rats because of withdrawal of sex hormones. Both RAL and RIS could treat osteoporosis in ORX rats; they reduced bone turnover markers and maintained BMD.
骨质疏松症是骨密度（BMD）降低。它在男性中比在女性中发生得较少。本研究旨在评估雷洛昔芬（RAL）、利塞膦酸盐（RIS）及其组合对骨质疏松症雄性大鼠的骨保护作用。40 只雄性 Wistar 大鼠（12 周）随机分为五组：假手术组（n = 8）、去势组（n = 7）、RAL 组（n = 9）、RIS 组（n = 7）和 RAL + RIS 组（n = 7）。RAL 经口给予 3mg/kg，每周 3 次，RIS 皮下给予 5μg/kg，每周 2 次。治疗 6 周后，测定血清组织蛋白酶-K、碱性（ALP）和酸性磷酸酶活性、血清骨钙素、血清 Ca²⁺和 Pi。测定尿 Ca²⁺和脱氧吡啶啉水平、股骨灰分的 BMD 和 Ca²⁺含量。检测胫骨 ALP 活性的组织化学定位和组织形态计量学。与假手术组相比，去势组大鼠的骨转换标志物显著增加，去势组大鼠胫骨近端的 ALP 组织化学活性显著增加，而去势组大鼠的股骨灰分 BMD 和 Ca²⁺含量降低。这些变化在 RAL 和 RIS 或两者治疗去势大鼠后得到调节；每种治疗均改善了股骨的 BMD，并且与去势载体组相比，骨转换标志物减少。我们得出结论，去势导致雄性大鼠骨质疏松症和骨转换增加，这是由于性激素的撤出。RAL 和 RIS 均可治疗去势大鼠的骨质疏松症；它们降低了骨转换标志物并维持了 BMD。
