School of Pharmacy, University of Mississippi, Jackson, Mississippi, USA.
Pharmacotherapy. 2010 Jul;30(7):716-27. doi: 10.1592/phco.30.7.716.
The increasing use of thiazolidinediones for the treatment of type 2 diabetes mellitus, coupled with the potential for fractures in the aging population, poses a significant concern for health care providers. This concern is based on many reports of postapproval adverse musculoskeletal effects, particularly bone changes and fractures. To better understand the effects of thiazolidinediones on bone health, we conducted a PubMed search of articles published from January 1966-June 2009. We reviewed the hypothesized mechanisms for thiazolidinedione-induced adverse effects on bone, studies that evaluated thiazolidinedione use and fracture risk, potential treatment options for fracture minimization, and future directions for research. Thiazolidinedione-induced bone changes may stem from the ability of these drugs to reduce the activity of osteoblasts without an appreciable effect on osteoclasts, shifting the balance of bone homeostasis to favor bone loss. Clinical data suggest that treating patients who have type 2 diabetes with thiazolidinediones has detrimental effects on bone health, as measured by reduced bone mineral density and increased fracture rates, notably distal extremity fractures in female patients. Thiazolidinediones are selective peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists; thus, continued pursuit of PPAR system selectivity and investigation of other PPAR agonists are crucial to understanding and avoiding these detrimental effects. Clinicians, particularly pharmacists, must take an active role in educating colleagues on the importance of screening thiazolidinedione-treated patients for fracture risk, counseling patients on adequate calcium and vitamin D intake and fall prevention, and appropriately selecting therapy for secondary prevention of fracture.
噻唑烷二酮类药物在 2 型糖尿病治疗中的应用日益增多，加之老年人群中骨折的潜在风险，这给医疗保健提供者带来了重大关注。这种关注基于许多关于批准后不良肌肉骨骼影响的报告，特别是骨变化和骨折。为了更好地了解噻唑烷二酮类药物对骨骼健康的影响，我们对 1966 年 1 月至 2009 年 6 月期间发表的文章进行了 PubMed 检索。我们综述了噻唑烷二酮类药物引起骨不良影响的假设机制、评估噻唑烷二酮类药物使用与骨折风险的研究、最小化骨折的潜在治疗选择以及未来的研究方向。噻唑烷二酮类药物引起的骨变化可能源于这些药物降低成骨细胞活性而对破骨细胞没有明显影响的能力，从而使骨稳态平衡偏向于骨质流失。临床数据表明，用噻唑烷二酮类药物治疗 2 型糖尿病患者会对骨骼健康产生不利影响，表现为骨密度降低和骨折发生率增加，尤其是女性患者的远端肢体骨折。噻唑烷二酮类药物是选择性过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂；因此，继续追求 PPAR 系统的选择性并研究其他 PPAR 激动剂对于理解和避免这些不利影响至关重要。临床医生，特别是药剂师，必须积极参与教育同事筛查噻唑烷二酮类药物治疗患者的骨折风险，为患者提供充足的钙和维生素 D 摄入和预防跌倒的建议，并为骨折的二级预防适当选择治疗方法。
