Rosiglitazone Decreases Bone Mass and Bone Marrow Fat
Rosiglitazone Decreases Bone Mass and Bone Marrow Fat
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DOI：
10.1210/jc.2010-2077
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发表时间：
2011-05-01
影响因子：
5.8
通讯作者：
Langdahl, Bente L.
中科院分区：
文献类型：
--
作者：
Harslof, Torben;Wamberg, Louise;Langdahl, Bente L.
背景：过氧化物酶体增殖激活受体γ的激活被认为促进骨髓间充质干细胞的脂肪细胞发育，以牺牲成骨细胞为代价，导致骨矿物质密度（BMD）降低和骨髓脂肪增加。目的：研究过氧化物酶体增殖体激活受体- γ激动剂罗格列酮对53名健康绝经后妇女双能x线骨密度评估和磁共振成像质子谱评估脊柱骨髓脂肪的影响。设计：这是一项为期14周的前瞻性、双盲、随机、安慰剂对照试验。背景：本研究在普通社区进行。患者：53名健康的绝经后妇女参加了这项研究。干预措施：罗格列酮片8mg /d。主要结局指标：主要终点为骨密度变化。结果：在股骨颈，罗格列酮组骨密度降低了1.34 +/- 0.60%（平均+/- SEM），而安慰剂组骨密度增加了0.28 +/- 0.56% （P = 0.055）。在腰椎，罗格列酮组骨密度下降1.03 +/- 0.34%，安慰剂组骨密度下降0.42 +/- 0.35% （P = 0.22）。骨吸收标志物羧基末端末端肽在罗格列酮组增加20.4 +/- 7.7%（平均+/- SEM），安慰剂组减少7.1 +/- 4.7% （P = 0.003）。罗格列酮组脊柱脂肪减少13.5 +/- 5.5%（平均+/- SEM），安慰剂组脊柱脂肪增加6.8 +/- 7.4% （P = 0.056）。结论：与预期相反，脊柱脂肪在罗格列酮治疗期间减少。此外，罗格列酮治疗导致骨吸收和形成失偶，导致骨质流失。我们的数据表明，骨髓成骨细胞与脂肪细胞的关系比以前认为的要复杂得多，这两种细胞类型可以独立地受到影响。[J] .中华内分泌杂志，2011,31(5):551 - 558。
Context: Activation of peroxisome proliferator-activated receptor-gamma is believed to promote adipocyte development from mesenchymal stem cells in the bone marrow at the expense of osteoblasts, leading to decreased bone mineral density (BMD) and increased marrow fat.Objective: The objective of the study was to examine the effect of the peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, on BMD assessed by dual-energy x-ray absorptiometry in 53 healthy postmenopausal women and spine bone marrow fat assessed by magnetic resonance imaging proton spectroscopy.Design: This was a 14-wk prospective, double-blind, randomized, placebo-controlled trial.Setting: The study was conducted in the general community.Patients: Fifty-three healthy postmenopausal women participated in the study.Intervention: Intervention included rosiglitazone tablets of 8 mg/d.Main Outcome Measures: The primary end point was a change in BMD.Results: At the femoral neck, BMD decreased by 1.34 +/- 0.60% (mean +/- SEM) in the rosiglitazone group, whereas BMD increased by 0.28 +/- 0.56% in the placebo group (P = 0.055). At the lumbar spine, BMD decreased by 1.03 +/- 0.34% in the rosiglitazone group and 0.42 +/- 0.35% in the placebo group (P = 0.22). The bone resorption marker carboxy-terminal telopeptide increased by 20.4 +/- 7.7% (mean +/- SEM) in the rosiglitazone group and decreased by 7.1 +/- 4.7% in the placebo group (P = 0.003). Spine fat decreased by 13.5 +/- 5.5% (mean +/- SEM) in the rosiglitazone group and increased by 6.8 +/- 7.4% in the placebo group (P = 0.056).Conclusions: Contrary to what was expected, spine fat decreased during rosiglitazone treatment. Furthermore, rosiglitazone treatment resulted in uncoupling of bone resorption and formation leading to bone loss. Our data suggest that the bone marrow osteoblast-adipocyte relationship is more complex than was assumed and that the two cell types can be independently affected. (J Clin Endocrinol Metab 96: 1541-1548, 2011)