Effects of Alfacalcidol on Mechanical Properties and Collagen Cross-Links of the Femoral Diaphysis in Glucocorticoid-Treated Rats
Effects of Alfacalcidol on Mechanical Properties and Collagen Cross-Links of the Femoral Diaphysis in Glucocorticoid-Treated Rats
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DOI：
10.1007/s00223-011-9472-6
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Shiraishi, Ayako
中科院分区：
文献类型：
--
作者：
Saito, Mitsuru;Marumo, Keishi;Shiraishi, Ayako
糖皮质激素（GC）诱导的骨量减少，即使GC治疗的患者有较高的骨矿物质密度（BMD），骨脆性增加，这表明受损的骨质量可能会影响骨强度。本研究旨在阐明GC对成年大鼠骨强度和胶原交联的影响，以及与活性维生素D（3）的前药阿法骨化醇（ALF）联合给药的影响。将6月龄雄性Wistar-Imamichi大鼠（n = 32）分为以下4组：（1）4周龄对照组;（2）4周龄GC（泼尼松龙，10 mg/kg，每日，i. m.）同时给予载体，（3）4周GC同时给予ALF（0.05 μ g/kg，每日，p.o.），和（4）伴随施用ALF（每天0.1 μ g/kg，p.o.）的4周GC。在治疗结束时，分析BMD、胶原交联、股骨中段的机械性能、骨代谢标志物和生化参数。GC组股骨骨强度下降，BMD无明显变化。这是伴随着酶交联的含量减少。ALF（0.1 μ g/kg）抑制GC诱导的骨强度降低。0.1 μ g/kg ALF组的成熟交联含量明显高于GC组。GC治疗导致骨代谢标志物和血清钙水平降低，这被ALF联合给药抵消。ALF预防性治疗抑制了骨机械性能的恶化，主要与酶交联形成的恢复和GC治疗对钙代谢的不良影响的改善有关。
Bone fragility is increased in glucocorticoid (GC)-induced osteopenia even though GC-treated patients have higher bone mineral density (BMD), suggesting that the impaired bone quality may affect bone strength. This study was conducted to clarify the effects of GC on bone strength and collagen cross-links of adult rats and the effect of coadministration of alfacalcidol (ALF), a prodrug of active vitamin D(3). Six-month-old male Wistar-Imamichi rats (n = 32) were divided into the following four groups with equal average body weight: (1) 4-week age-matched controls, (2) 4-week GC (prednisolone, 10 mg/kg daily, i.m.) with concomitant administration of vehicle, (3) 4-week GC with concomitant administration of ALF (0.05 mu g/kg daily, p.o.), and (4) 4-week GC with concomitant administration of ALF (0.1 mu g/kg daily, p.o.). At the end of treatment, BMD, collagen cross-links, mechanical properties of the femoral midshaft, bone metabolic markers, and biochemical parameters were analyzed. In the GC group, femoral bone strength decreased without any change of BMD. This was accompanied by a decrease in the content of enzymatic cross-links. ALF (0.1 mu g/kg) inhibited the GC-induced reduction in bone strength. The content of mature cross-links in the 0.1-mu g/kg ALF group was significantly higher than that in the GC group. GC treatment caused a decrease in bone metabolic markers and serum calcium levels, which was counteracted by ALF coadministration. Preventive treatment with ALF inhibited the deterioration of bone mechanical properties primarily in association with the restoration of enzymatic cross-link formation and amelioration of the adverse effects of GC treatment on calcium metabolism.