Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary osteoporosis.
Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary osteoporosis.
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DOI：
10.1007/s11914-010-0027-y
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发表时间：
2010-12
影响因子：
4.3
通讯作者：
Lecka-Czernik, Beata
中科院分区：
文献类型：
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作者：
Lecka-Czernik, Beata
临床证据表明，2型糖尿病（T2 DM）患者的骨状态受到影响。无论骨密度正常甚至高，T2 DM患者骨折的风险都增加。一类抗糖尿病药物噻唑烷二酮类（TZD）可导致骨丢失，并进一步增加骨折风险，将TZD置于导致继发性骨质疏松症的药物类别中。TZD诱发继发性骨质疏松症的风险因素包括性别（女性）、年龄（老年人）和治疗持续时间。TZD通过激活过氧化物酶体增殖物激活受体-γ（PPAR-γ）核受体发挥其抗糖尿病作用，该受体控制葡萄糖和脂肪酸代谢。在骨中，PPAR-γ控制间充质和造血谱系细胞的分化。TZD激活PPAR-γ导致骨重建失衡：骨吸收增加，骨形成减少。实验室研究证据表明，通过使用选择性PPAR-γ调节剂，可能将PPAR-γ对骨的不良影响与其有益的抗糖尿病作用分开。本综述还讨论了潜在的药理学手段，以保护骨免受不利影响的临床使用的TZDs（吡格列酮和罗格列酮），通过使用批准的抗糖尿病药物的联合治疗，或通过使用较低剂量的TZDs与其他抗糖尿病治疗相结合。我们还提出了一种可能的骨科并发症，尚未得到临床研究的支持，即TZD治疗的T2 DM患者骨折愈合延迟。
Clinical evidence indicates that bone status is affected in patients with type 2 diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density, T2DM patients have increased risk of fractures. One class of antidiabetic drugs, thiazolidinediones (TZDs), causes bone loss and further increases facture risk, placing TZDs in the category of drugs causing secondary osteoporosis. Risk factors for development of TZD-induced secondary osteoporosis are gender (women), age (elderly), and duration of treatment. TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR-γ controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-γ activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases. Laboratory research evidence points toward a possible separation of unwanted effects of PPAR-γ on bone from its beneficial antidiabetic effects by using selective PPAR-γ modulators. This review also discusses potential pharmacologic means to protect bone from detrimental effects of clinically used TZDs (pioglitazone and rosiglitazone) by using combinational therapy with approved antiosteoporotic drugs, or by using lower doses of TZDs in combination with other antidiabetic therapy. We also suggest a possible orthopedic complication, not yet supported by clinical studies, of delayed fracture healing in T2DM patients on TZD therapy.